[h1]Introduction - University of Dundee
Gastrointestinal diagnosis using non-white light imaging capsule endoscopyGerard Cummins1, Benjamin F Cox2, Gastone Ciuti3, Thineskrishna Anbarasan2, Marc P.Y. Desmulliez1, Sandy Cochran4, Robert Steele2, John N Plevris5, Anastasios Koulaouzidis6*email: g.cummins@hw.ac.uk1.School of Engineering and Physical SciencesHeriot-Watt University EdinburghUnited Kingdom2. School of MedicineUniversity of DundeeDundeeUnited Kingdom3. The BioRobotics InstituteScuola Superiore Sant'AnnaPisaItaly4. School of EngineeringUniversity of GlasgowGlasgowUnited Kingdom5. Centre for Liver and Digestive DisordersThe Royal Infirmary of EdinburghEdinburghUnited Kingdom6. Endoscopy UnitThe Royal Infirmary of EdinburghEdinburgh United KingdomKey points:White light imaging (WLI) remains the dominant diagnostic modality in capsule endoscopy after nearly two decades of clinical use.WLI technology limits diagnosis to the mucosal surface of the gut due to the limited penetration depth of optical wavelengths beyond the tissue surface In the past fewyears there has been an increase in the application of non-WLI diagnostic imaging and sensing technologies to capsule endoscopy, some of which are at a more advanced stage of testing than others. Integrating specific diagnostic imaging technologies into capsule endoscopy devices enables submucosal imaging, improved differentiation between malignant and benign tissue and new avenues for investigating the aetiology of disease. Many of these capsules require further testing to determine their clinical efficacy fully due to the small sample sizes of the reported studies. New diagnostic capsule designs will provide new opportunities for improved computer-aided diagnosis, virtual biopsy and capsule localization that could benefit clinical practice in the future. AbstractCapsule endoscopy (CE) has proved to be a powerful tool in the diagnosis and management of small bowel disorders since its introduction in 2001. However, white light imaging (WLI) is the principal technology used in clinical CE at present, and therefore, CE is limited to mucosal inspection, with diagnosis remaining reliant on visible manifestations of disease. The introduction of WLI CE has motivated a wide range of research to improve its diagnostic capabilities through integration with other sensing modalities. These developments have the potential to overcome the limitations of WLI through enhanced detection of subtle mucosal microlesions and submucosal and/or transmural pathology , providing novel diagnostic avenues. Other research aims to utilize a range of sensors to measure physiological parameters or to discover new biomarkers to improve the sensitivity , specificity and thus the clinical utility of CE. This multidisciplinary Review summarizes research into non- WLI CE devices by organizing them into a taxonomic structure on the basis of their sensing modality. The potential of these capsules to realize clinically useful virtual biopsy and computer- aided diagnosis (CADx) is also reported.Capsule endoscopy (CE) has proven to be a powerful tool in the diagnosis and management of small bowel disorders since its introduction in 2001. However, white light imaging (WLI) is the principal technology used in clinical CE at present and therefore is limited solely to mucosal inspection with diagnosis remaining reliant on visible manifestations of disease. The introduction of WLI CE has motivated a wide range of research to improve its diagnostic capabilities through integration with other sensing modalities. These developments have the potential to overcome the limitations of WLI through enhanced detection of subtle mucosal microlesions and submucosal and/or transmural pathology, providing novel diagnostic avenues. Other research aims to utilize a range of sensors to measure physiological parameters or to discover new biomarkers to improve the sensitivity, specificity and thus the clinical utility of CE. This multidisciplinary Review summarizes research into non-WLI CE devices by organizing them into a taxonomic structure on the basis of their sensing modality. The potential of these capsules to realize clinically useful virtual biopsy and computer-aided diagnosis (CADx) is also reported.[h1]IntroductionCapsule endoscopy (CE) offers a minimally invasive method to visualize the gastrointestinal (GI) tract. The first CE system approved for clinical use was the M2A capsule (Given Imaging, Yoqneam, Israel) in 2001ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1053/j.gastro.2016.12.032","ISBN":"1528-0012 (Electronic) 0016-5085 (Linking)","ISSN":"00165085","PMID":"28063287","abstract":"Background & Aims Video capsule endoscopy (CE) provides a noninvasive option to assess the small intestine, but its use with respect to endoscopic procedures and cross-sectional imaging varies widely. The aim of this consensus was to provide guidance on the appropriate use of CE in clinical practice. Methods A systematic literature search identified studies on the use of CE in patients with Crohn's disease, celiac disease, gastrointestinal bleeding, and anemia. The quality of evidence and strength of recommendations were rated using the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Results The consensus includes 21 statements focused on the use of small-bowel CE and colon capsule endoscopy. CE was recommended for patients with suspected, known, or relapsed Crohn's disease when ileocolonoscopy and imaging studies were negative if it was imperative to know whether active Crohn's disease was present in the small bowel. It was not recommended in patients with chronic abdominal pain or diarrhea, in whom there was no evidence of abnormal biomarkers typically associated with Crohn's disease. CE was recommended to assess patients with celiac disease who have unexplained symptoms despite appropriate treatment, but not to make the diagnosis. In patients with overt gastrointestinal bleeding, and negative findings on esophagogastroduodenoscopy and colonoscopy, CE should be performed as soon as possible. CE was recommended only in selected patients with unexplained, mild, chronic iron-deficiency anemia. CE was suggested for surveillance in patients with polyposis syndromes or other small-bowel cancers, who required small-bowel studies. Colon capsule endoscopy should not be substituted routinely for colonoscopy. Patients should be made aware of the potential risks of CE including a failed procedure, capsule retention, or a missed lesion. Finally, standardized criteria for training and reporting in CE should be defined. Conclusions CE generally should be considered a complementary test in patients with gastrointestinal bleeding, Crohn's disease, or celiac disease, who have had negative or inconclusive endoscopic or imaging studies.","author":[{"dropping-particle":"","family":"Enns","given":"Robert A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hookey","given":"Lawrence","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Armstrong","given":"David","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bernstein","given":"Charles N.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Heitman","given":"Steven J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Teshima","given":"Christopher","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leontiadis","given":"Grigorios I.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tse","given":"Frances","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sadowski","given":"Daniel","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastroenterology","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2017","2"]]},"page":"497-514","publisher":"Elsevier","title":"Clinical Practice Guidelines for the Use of Video Capsule?Endoscopy","type":"article-journal","volume":"152"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>1</sup>","plainTextFormattedCitation":"1","previouslyFormattedCitation":"<sup>1</sup>"},"properties":{"noteIndex":0},"schema":""}1ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"author":[{"dropping-particle":"","family":"Iddan","given":"G","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Meron","given":"G","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Glukhovsky","given":"A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Swain","given":"P","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Nature","id":"ITEM-1","issue":"May","issued":{"date-parts":[["2000"]]},"page":"417-418","title":"Wireless capsule endoscopy","type":"article-journal","volume":"405"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>1</sup>","plainTextFormattedCitation":"1","previouslyFormattedCitation":"<sup>1</sup>"},"properties":{"noteIndex":0},"schema":""}1. Since then, several companies have introduced CE systemsADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.3748/wjg.v21.i17.5119","ISSN":"22192840","PMID":"25954085","abstract":"Currently, the major problem of all existing commercial capsule devices is the lack of control of movement. In the future, with an interface application, the clinician will be able to stop and direct the device into points of interest for detailed inspection/diagnosis, ...","author":[{"dropping-particle":"","family":"Koulaouzidis","given":"Anastasios","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Iakovidis","given":"Dimitris K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Karargyris","given":"Alexandros","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rondonotti","given":"Emanuele","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"World Journal of Gastroenterology","id":"ITEM-1","issue":"17","issued":{"date-parts":[["2015"]]},"page":"5119-5130","title":"Wireless endoscopy in 2020: Will it still be a capsule?","type":"article-journal","volume":"21"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>2</sup>","plainTextFormattedCitation":"2","previouslyFormattedCitation":"<sup>2</sup>"},"properties":{"noteIndex":0},"schema":""}2. As shown in REF _Ref513018658 \h \* MERGEFORMAT Table 1, commercially available CE systems primarily rely on white light imaging (WLI), which images the mucosal surface with light within the visible spectrum to enable evaluation of the gastrointestinal lumen and mucosa. CE has been investigated as a diagnostic tool for gastrointestinal diseases, such as bleeding, IBD, colorectal cancer (CRC) and Barrett’s esophagusoesophagus, with varying degrees of success. Further developments in CE technology have explored the feasibility of other imaging modalities such as microultrasonography (μUS)ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.21037/atm.2017.04.21","ISSN":"23055839","abstract":"Video capsule endoscopy (VCE) has been of immense benefit in the diagnosis and management of gastrointestinal (GI) disorders since its introduction in 2001. However, it suffers from a number of well recognized deficiencies. Amongst these is the limited capability of white light imaging, which is restricted to analysis of the mucosal surface. Current capsule endoscopes are dependent on visual manifestation of disease and limited in regards to transmural imaging and detection of deeper pathology. Ultrasound capsule endoscopy (USCE) has the potential to overcome surface only imaging and provide transmural scans of the GI tract. The integration of high frequency microultrasound (?US) into capsule endoscopy would allow high resolution transmural images and provide a means of both qualitative and quantitative assessment of the bowel wall. Quantitative ultrasound (QUS) can provide data in an objective and measurable manner, potentially reducing lengthy interpretation times by incorporation into an automated diagnostic process. The research described here is focused on the development of USCE and other complementary diagnostic and therapeutic modalities. Presently investigations have entered a preclinical phase with laboratory investigations running concurrently.","author":[{"dropping-particle":"","family":"Cox","given":"Benjamin F. B.F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stewart","given":"Fraser","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lay","given":"Holly","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cummins","given":"Gerard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Newton","given":"I.P. Ian P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Desmulliez","given":"Marc P. Y. M.P. Y.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Steele","given":"R.J. C. Robert J. C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nthke?","given":"I.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cochran","given":"Sandy","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"N?thke","given":"Inke","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cochran","given":"Sandy","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Annals of Translational Medicine","id":"ITEM-1","issue":"9","issued":{"date-parts":[["2017","5"]]},"page":"201-201","title":"Ultrasound capsule endoscopy: sounding out the future","type":"article-journal","volume":"5"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1109/TBME.2018.2852715","ISSN":"0018-9294","author":[{"dropping-particle":"","family":"Lay","given":"Holly","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cummins","given":"Gerard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cox","given":"Benjamin F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Qiu","given":"Yongqiang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Turcanu","given":"Mihnea Vlad","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"McPhillips","given":"Rachael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Connor","given":"Ciaran","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gregson","given":"Rachael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Clutton","given":"Eddie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Desmulliez","given":"Marc P.Y.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cochran","given":"Sandy","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Transactions on Biomedical Engineering","id":"ITEM-2","issue":"3","issued":{"date-parts":[["2018"]]},"page":"632 - 639","title":"In-Vivo Evaluation of Microultrasound and Thermometric Capsule Endoscopes","type":"article-journal","volume":"66"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>3,4</sup>","plainTextFormattedCitation":"3,4","previouslyFormattedCitation":"<sup>3,4</sup>"},"properties":{"noteIndex":0},"schema":""}3,4 and infrared lightADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.gie.2008.02.023","ISSN":"00165107","PMID":"18499106","abstract":"BACKGROUND Current capsule endoscopy (CE) provides minimally invasive technology for GI imaging but has limited ability to discriminate different types of polyps. Near infrared fluorescent (NIRF) probes activated by biomarkers upregulated in adenomas (eg, cathepsin B) are potentially powerful tools to distinguish premalignant or malignant lesions from benign or inflammatory lesions. OBJECTIVES To examine whether CE can be integrated with NIRF probes to detect adenomas and whether cathepsin B-activated NIRF probes are activated by benign or inflammatory lesions. DESIGN Mouse models of adenomas, hyperplactic/lymphoid polyps, and acute or chronic intestinal inflammation were injected intravenously with a cathepsin B-activated probe (Prosense 680). Dissected intestine was imaged with CE under white or NIRF light. For NIRF excitation (680 nm), dichroic and emission (700 nm) filters were combined with CE when images were recorded. Prosense 680 samples with or without protease were used as positive and negative controls. CE-based imaging data were verified by using and independent imaging system (Xenogen IVIS system). MAIN OUTCOME MEASUREMENTS Proof of principal that CE integrated with NIRF probes can detect and discriminate adenomas from other lesions. RESULTS CE-based NIRF imaging with Prosense 680 readily visualized adenomas, including in the colitis model. NIRF signals of different intensities were detected. Prosense 680 was not activated by benign or inflammatory lesions. LIMITATION Optical filters external to the capsule were used. CONCLUSIONS We demonstrate proof of the principle that biochromoendoscopy-CE combined with molecular probes--provides a novel approach that differentiates adenomas from benign polyps and inflammatory lesions.","author":[{"dropping-particle":"","family":"Zhang","given":"Howard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Morgan","given":"Douglas","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cecil","given":"Gerald","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Burkholder","given":"Adam","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ramocki","given":"Nicole","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Scull","given":"Brooks","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lund","given":"P Kay","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastrointestinal Endoscopy","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2008","9"]]},"page":"520-527","publisher":"NIH Public Access","title":"Biochromoendoscopy: molecular imaging with capsule endoscopy for detection of adenomas of the GI tract","type":"article-journal","volume":"68"},"uris":["",""]}],"mendeley":{"formattedCitation":"<sup>5</sup>","plainTextFormattedCitation":"5","previouslyFormattedCitation":"<sup>5</sup>"},"properties":{"noteIndex":0},"schema":""}5. Despite the potential offered by these alternative imaging modalities, WLI CE remains most widely used and studied in clinical practiceADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1053/j.gastro.2016.12.032","ISBN":"1528-0012 (Electronic) 0016-5085 (Linking)","ISSN":"00165085","PMID":"28063287","abstract":"Background & Aims Video capsule endoscopy (CE) provides a noninvasive option to assess the small intestine, but its use with respect to endoscopic procedures and cross-sectional imaging varies widely. The aim of this consensus was to provide guidance on the appropriate use of CE in clinical practice. Methods A systematic literature search identified studies on the use of CE in patients with Crohn's disease, celiac disease, gastrointestinal bleeding, and anemia. The quality of evidence and strength of recommendations were rated using the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Results The consensus includes 21 statements focused on the use of small-bowel CE and colon capsule endoscopy. CE was recommended for patients with suspected, known, or relapsed Crohn's disease when ileocolonoscopy and imaging studies were negative if it was imperative to know whether active Crohn's disease was present in the small bowel. It was not recommended in patients with chronic abdominal pain or diarrhea, in whom there was no evidence of abnormal biomarkers typically associated with Crohn's disease. CE was recommended to assess patients with celiac disease who have unexplained symptoms despite appropriate treatment, but not to make the diagnosis. In patients with overt gastrointestinal bleeding, and negative findings on esophagogastroduodenoscopy and colonoscopy, CE should be performed as soon as possible. CE was recommended only in selected patients with unexplained, mild, chronic iron-deficiency anemia. CE was suggested for surveillance in patients with polyposis syndromes or other small-bowel cancers, who required small-bowel studies. Colon capsule endoscopy should not be substituted routinely for colonoscopy. Patients should be made aware of the potential risks of CE including a failed procedure, capsule retention, or a missed lesion. Finally, standardized criteria for training and reporting in CE should be defined. Conclusions CE generally should be considered a complementary test in patients with gastrointestinal bleeding, Crohn's disease, or celiac disease, who have had negative or inconclusive endoscopic or imaging studies.","author":[{"dropping-particle":"","family":"Enns","given":"Robert A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hookey","given":"Lawrence","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Armstrong","given":"David","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bernstein","given":"Charles N.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Heitman","given":"Steven J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Teshima","given":"Christopher","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leontiadis","given":"Grigorios I.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tse","given":"Frances","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sadowski","given":"Daniel","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastroenterology","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2017","2"]]},"page":"497-514","publisher":"Elsevier","title":"Clinical Practice Guidelines for the Use of Video Capsule Endoscopy","type":"article-journal","volume":"152"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1055/s-0034-1391855","ISSN":"0013-726X","PMID":"25826168","abstract":"This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). The Guideline was also reviewed and endorsed by the British Society of Gastroenterology (BSG). It addresses the roles of small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders. Main recommendations 1 ESGE recommends small-bowel video capsule endoscopy as the first-line investigation in patients with obscure gastrointestinal bleeding (strong recommendation, moderate quality evidence). 2 In patients with overt obscure gastrointestinal bleeding, ESGE recommends performing small-bowel capsule endoscopy as soon as possible after the bleeding episode, optimally within 14 days, in order to maximize the diagnostic yield (strong recommendation, moderate quality evidence). 3 ESGE does not recommend the routine performance of second-look endoscopy prior to small-bowel capsule endoscopy; however whether to perform second-look endoscopy before capsule endoscopy in patients with obscure gastrointestinal bleeding or iron-deficiency anaemia should be decided on a case-by-case basis (strong recommendation, low quality evidence). 4 In patients with positive findings at small-bowel capsule endoscopy, ESGE recommends device-assisted enteroscopy to confirm and possibly treat lesions identified by capsule endoscopy (strong recommendation, high quality evidence). 5 ESGE recommends ileocolonoscopy as the first endoscopic examination for investigating patients with suspected Crohn's disease (strong recommendation, high quality evidence). In patients with suspected Crohn's disease and negative ileocolonoscopy findings, ESGE recommends small-bowel capsule endoscopy as the initial diagnostic modality for investigating the small bowel, in the absence of obstructive symptoms or known stenosis (strong recommendation, moderate quality evidence).ESGE does not recommend routine small-bowel imaging or the use of the PillCam patency capsule prior to capsule endoscopy in these patients (strong recommendation, low quality evidence). In the presence of obstructive symptoms or known stenosis, ESGE recommends that dedicated small bowel cross-sectional imaging modalities such as magnetic resonance enterography/enteroclysis or computed tomography enterography/enteroclysis should be used first (strong recommendation, low quality evidence). 6 In patients with established Crohn's disease, based on ileocolonoscopy findings, ESGE recommends …","author":[{"dropping-particle":"","family":"Pennazio","given":"Marco","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Spada","given":"Cristiano","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Eliakim","given":"Rami","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Keuchel","given":"Martin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"May","given":"Andrea","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mulder","given":"Chris","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rondonotti","given":"Emanuele","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Adler","given":"Samuel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Albert","given":"Joerg","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Baltes","given":"Peter","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Barbaro","given":"Federico","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cellier","given":"Christophe","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Charton","given":"Jean","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Delvaux","given":"Michel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Despott","given":"Edward","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Domagk","given":"Dirk","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Klein","given":"Amir","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"McAlindon","given":"Mark","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rosa","given":"Bruno","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rowse","given":"Georgina","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sanders","given":"David","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Saurin","given":"Jean","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sidhu","given":"Reena","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dumonceau","given":"Jean-Marc","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hassan","given":"Cesare","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gralnek","given":"Ian","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Endoscopy","id":"ITEM-2","issue":"04","issued":{"date-parts":[["2015","3","31"]]},"page":"352-386","title":"Small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline","type":"article-journal","volume":"47"},"uris":["",""]}],"mendeley":{"formattedCitation":"<sup>6,7</sup>","plainTextFormattedCitation":"6,7","previouslyFormattedCitation":"<sup>6,7</sup>"},"properties":{"noteIndex":0},"schema":""}6,7. This Review discusses the limitations of conventional WLI CE in the diagnosis of gastrointestinal disease and gives an overview of the non-WLI capsules currently available on the market or progressing towards clinical translation. [H1]Clinical Use of Capsule Endoscopy The ability to investigate small bowel pathology, particularly in segments inaccessible by conventional endoscopy, has been the cardinal motive for the development of WLI CE systems. Additional advantages of CE over conventional endoscopy include removing the need for patient sedation, increased patient acceptance and reduced costsADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.4253/wjge.v7.i1.13","ISBN":"1948-5190 (Electronic)","ISSN":"1948-5190","PMID":"25610531","abstract":"The development of capsule endoscopy (CE) in 2001 has given gastroenterologists the opportunity to investigate the small bowel in a non-invasive way. CE is most commonly performed for obscure gastrointestinal bleeding, but other indications include diagnosis or follow-up of Crohn's disease, suspicion of a small bowel tumor, diagnosis and surveillance of hereditary polyposis syndromes, Nonsteroidal anti-inflammatory drug-induced small bowel lesions and celiac disease. Almost fifteen years have passed since the release of the small bowel capsule. The purpose of this review is to offer the reader a brief but complete overview on small bowel CE anno 2014, including the technical and procedural aspects, the possible complications and the most important indications. We will end with some future perspectives of CE.","author":[{"dropping-particle":"Van de","family":"Bruaene","given":"Cedric","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"World Journal of Gastrointestinal Endoscopy","id":"ITEM-1","issued":{"date-parts":[["2015"]]},"title":"Small bowel capsule endoscopy: Where are we after almost 15 years of use?","type":"article-journal"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.21037/atm.2017.10.20","ISSN":"23055839","author":[{"dropping-particle":"","family":"Nowak","given":"Tanja","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Annals of Translational Medicine","id":"ITEM-2","issue":"21","issued":{"date-parts":[["2017","11"]]},"page":"422-422","title":"A global perspective on capsule endoscopy","type":"article-journal","volume":"5"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.3748/wjg.v20.i23.7424","ISSN":"22192840","PMID":"24966612","abstract":"Capsule endoscopy is nowadays the diagnostic technique of choice in the study of small bowel pathologies, allowing the non-invasive study of the entire mucosa. This has led, together with new technical advances, to the creation of two new models (PillCam ESO and PillCam Colon) for the study of esophageal and colonic diseases. These two new capsules offer an interesting alternative to conventional endoscopy in the study of the upper and lower digestive tracts, because traditional endoscopy is often unpleasant and uncomfortable for the patient, can be painful, often requires moderate or deep sedation and is not without complications (hemorrhage, perforation, etc.). PillCam Colon is particularly important for its usefulness in the diagnosis of colonic polyps, and is a potentially useful tool in cases of incomplete colonoscopy or in colorectal cancer screening, even more when most patients are reluctant to undergo screening programs due to the said disadvantages of conventional colonoscopy. This article discusses the advantages of capsule endoscopy over conventional endoscopy, its current application possibilities and indications in routine clinical practice. In the various sections of the work, we assess the application of endoscopic capsule in different sections of the digestive tract (esophagus, stomach, and colon) and finally the potential role of panendoscopy with PillCam Colon.","author":[{"dropping-particle":"","family":"Romero-Vázquez","given":"Javier","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Argüelles-Arias","given":"Federico","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"García-Montes","given":"Josefa Maria","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Caunedo-?lvarez","given":"?ngel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pellicer-Bautista","given":"Francisco Javier","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Herrerías-Gutiérrez","given":"Juan Manuel","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"World Journal of Gastroenterology","id":"ITEM-3","issued":{"date-parts":[["2014"]]},"title":"Capsule endoscopy in patients refusing conventional endoscopy","type":"article"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>8–10</sup>","plainTextFormattedCitation":"8–10","previouslyFormattedCitation":"<sup>8–10</sup>"},"properties":{"noteIndex":0},"schema":""}8–10. Recommendations for the use of CE systems in the colon remain primarily confined to surveillance for patients with an incomplete assessment or contraindications to conventional endoscopy, which is more sensitive and offer interventional optionsADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1053/j.gastro.2016.12.032","ISBN":"1528-0012 (Electronic) 0016-5085 (Linking)","ISSN":"00165085","PMID":"28063287","abstract":"Background & Aims Video capsule endoscopy (CE) provides a noninvasive option to assess the small intestine, but its use with respect to endoscopic procedures and cross-sectional imaging varies widely. The aim of this consensus was to provide guidance on the appropriate use of CE in clinical practice. Methods A systematic literature search identified studies on the use of CE in patients with Crohn's disease, celiac disease, gastrointestinal bleeding, and anemia. The quality of evidence and strength of recommendations were rated using the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Results The consensus includes 21 statements focused on the use of small-bowel CE and colon capsule endoscopy. CE was recommended for patients with suspected, known, or relapsed Crohn's disease when ileocolonoscopy and imaging studies were negative if it was imperative to know whether active Crohn's disease was present in the small bowel. It was not recommended in patients with chronic abdominal pain or diarrhea, in whom there was no evidence of abnormal biomarkers typically associated with Crohn's disease. CE was recommended to assess patients with celiac disease who have unexplained symptoms despite appropriate treatment, but not to make the diagnosis. In patients with overt gastrointestinal bleeding, and negative findings on esophagogastroduodenoscopy and colonoscopy, CE should be performed as soon as possible. CE was recommended only in selected patients with unexplained, mild, chronic iron-deficiency anemia. CE was suggested for surveillance in patients with polyposis syndromes or other small-bowel cancers, who required small-bowel studies. Colon capsule endoscopy should not be substituted routinely for colonoscopy. Patients should be made aware of the potential risks of CE including a failed procedure, capsule retention, or a missed lesion. Finally, standardized criteria for training and reporting in CE should be defined. Conclusions CE generally should be considered a complementary test in patients with gastrointestinal bleeding, Crohn's disease, or celiac disease, who have had negative or inconclusive endoscopic or imaging studies.","author":[{"dropping-particle":"","family":"Enns","given":"Robert A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hookey","given":"Lawrence","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Armstrong","given":"David","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bernstein","given":"Charles N.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Heitman","given":"Steven J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Teshima","given":"Christopher","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leontiadis","given":"Grigorios I.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tse","given":"Frances","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sadowski","given":"Daniel","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastroenterology","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2017","2"]]},"page":"497-514","publisher":"Elsevier","title":"Clinical Practice Guidelines for the Use of Video Capsule?Endoscopy","type":"article-journal","volume":"152"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>1</sup>","plainTextFormattedCitation":"1","previouslyFormattedCitation":"<sup>1</sup>"},"properties":{"noteIndex":0},"schema":""}1ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1053/j.gastro.2016.12.032","ISBN":"1528-0012 (Electronic) 0016-5085 (Linking)","ISSN":"00165085","PMID":"28063287","abstract":"Background & Aims Video capsule endoscopy (CE) provides a noninvasive option to assess the small intestine, but its use with respect to endoscopic procedures and cross-sectional imaging varies widely. The aim of this consensus was to provide guidance on the appropriate use of CE in clinical practice. Methods A systematic literature search identified studies on the use of CE in patients with Crohn's disease, celiac disease, gastrointestinal bleeding, and anemia. The quality of evidence and strength of recommendations were rated using the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Results The consensus includes 21 statements focused on the use of small-bowel CE and colon capsule endoscopy. CE was recommended for patients with suspected, known, or relapsed Crohn's disease when ileocolonoscopy and imaging studies were negative if it was imperative to know whether active Crohn's disease was present in the small bowel. It was not recommended in patients with chronic abdominal pain or diarrhea, in whom there was no evidence of abnormal biomarkers typically associated with Crohn's disease. CE was recommended to assess patients with celiac disease who have unexplained symptoms despite appropriate treatment, but not to make the diagnosis. In patients with overt gastrointestinal bleeding, and negative findings on esophagogastroduodenoscopy and colonoscopy, CE should be performed as soon as possible. CE was recommended only in selected patients with unexplained, mild, chronic iron-deficiency anemia. CE was suggested for surveillance in patients with polyposis syndromes or other small-bowel cancers, who required small-bowel studies. Colon capsule endoscopy should not be substituted routinely for colonoscopy. Patients should be made aware of the potential risks of CE including a failed procedure, capsule retention, or a missed lesion. Finally, standardized criteria for training and reporting in CE should be defined. Conclusions CE generally should be considered a complementary test in patients with gastrointestinal bleeding, Crohn's disease, or celiac disease, who have had negative or inconclusive endoscopic or imaging studies.","author":[{"dropping-particle":"","family":"Enns","given":"Robert A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hookey","given":"Lawrence","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Armstrong","given":"David","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bernstein","given":"Charles N.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Heitman","given":"Steven J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Teshima","given":"Christopher","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leontiadis","given":"Grigorios I.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tse","given":"Frances","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sadowski","given":"Daniel","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastroenterology","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2017","2"]]},"page":"497-514","publisher":"Elsevier","title":"Clinical Practice Guidelines for the Use of Video Capsule?Endoscopy","type":"article-journal","volume":"152"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>11</sup>","plainTextFormattedCitation":"11","previouslyFormattedCitation":"<sup>11</sup>"},"properties":{"noteIndex":0},"schema":""}11. Guidelines for the use of CE in clinical practice provided by the European Society of Gastroenterology (ESGE) and the American Gastroenterological Association (AGA) are summarized in REF _Ref410415426 \h Table 2. An overview of the evidence basis for the use of CE in the diagnosis of various pathologies is provided in Supplementary Table 1.[H2]Small BowelIn a meta-analysis comprising 396 patients with small bowel bleeding, the use of CE was associated with superior diagnostic yield (DY) compared with both enteroscopy and small bowel radiographyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/j.1572-0241.2005.00274.x","ISSN":"0002-9270","PMID":"16279893","abstract":"OBJECTIVES Due to its superior ability to examine the entire small bowel mucosa, capsule endoscopy (CE) has broadened the diagnostic evaluation of patients with obscure gastrointestinal bleeding (OGIB). Published studies have revealed a numerically superior performance of CE in determining a source of OGIB compared with other modalities, but due to small sample sizes, the overall magnitude of benefit is unknown. Additionally, the types of lesions more likely to be found by CE versus alternate modalities are also unknown. The aim of this study was to evaluate the yield of small bowel findings with CE in patients with OGIB compared to other modalities using meta-analysis. METHODS We performed a recursive literature search of prospective studies comparing the yield of CE to other modalities in patients with OGIB. Data on yield and types of lesions identified among various modalities were extracted, pooled, and analyzed. Incremental yield (IY) (yield of CE-yield of comparative modality) and 95% confidence intervals (95% CI) of CE over comparative modalities were calculated. RESULTS A total of 14 studies (n = 396) compared the yield of CE with push enteroscopy for OGIB. The yield for CE and push enteroscopy was 63% and 28%, respectively (IY = 35%, p < 0.00001, 95% CI = 26-43%) and for clinically significant findings (n = 376) was 56% and 26%, respectively (IY = 30%, p < 0.00001, 95% CI = 21-38%). Three studies (n = 88) compared the yield of CE to small bowel barium radiography. The yield for CE and small bowel barium radiography for any finding was 67% and 8%, respectively (IY = 59%, p < 0.00001, 95% CI = 48-70%) and for clinically significant findings was 42% and 6%, respectively (IY = 36%, p < 0.00001, 95% CI = 25-48%). Number needed to test (NNT) to yield one additional clinically significant finding with CE over either modality was 3 (95% CI = 2-4). One study each compared the yield of significant findings on CE to intraoperative enteroscopy (n = 42, IY = 0%, p= 1.0, 95% CI =-16% to 16%), computed tomography enteroclysis (n = 8, IY = 38%, p= 0.08, 95% CI =-4% to 79%), mesenteric angiogram (n = 17, IY =-6%, p= 0.73, 95% CI =-39% to 28%), and small bowel magnetic resonance imaging (n = 14, IY = 36%, p= 0.007, 95% CI = 10-62%). Ten of the 14 trials comparing CE with push enteroscopy classified the types of lesions found on examination. CE had a 36% yield for vascular lesions versus 20% for push enteroscopy, with an IY of 16% (p < 0.00001, 95% CI = 9-23%). I…","author":[{"dropping-particle":"","family":"Triester","given":"Stuart L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leighton","given":"Jonathan A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leontiadis","given":"Grigoris I.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fleischer","given":"David E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hara","given":"Amy K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Heigh","given":"Russell I.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shiff","given":"Arthur D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sharma","given":"Virender K.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"The American Journal of Gastroenterology","id":"ITEM-1","issue":"11","issued":{"date-parts":[["2005","11"]]},"page":"2407-2418","title":"A Meta-Analysis of the Yield of Capsule Endoscopy Compared to Other Diagnostic Modalities in Patients with Obscure Gastrointestinal Bleeding","type":"article-journal","volume":"100"},"uris":["",""]}],"mendeley":{"formattedCitation":"<sup>11</sup>","plainTextFormattedCitation":"11","previouslyFormattedCitation":"<sup>11</sup>"},"properties":{"noteIndex":0},"schema":""}11. CE is therefore recommended as the first-line investigation modality for obscure gastrointestinal bleeding (OGIB), which is defined as gastrointestinal tract bleeding of untraceable origin on esophagogastroduodenoscopy (EGD) and colonoscopyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1053/j.gastro.2016.12.032","ISBN":"1528-0012 (Electronic) 0016-5085 (Linking)","ISSN":"00165085","PMID":"28063287","abstract":"Background & Aims Video capsule endoscopy (CE) provides a noninvasive option to assess the small intestine, but its use with respect to endoscopic procedures and cross-sectional imaging varies widely. The aim of this consensus was to provide guidance on the appropriate use of CE in clinical practice. Methods A systematic literature search identified studies on the use of CE in patients with Crohn's disease, celiac disease, gastrointestinal bleeding, and anemia. The quality of evidence and strength of recommendations were rated using the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Results The consensus includes 21 statements focused on the use of small-bowel CE and colon capsule endoscopy. CE was recommended for patients with suspected, known, or relapsed Crohn's disease when ileocolonoscopy and imaging studies were negative if it was imperative to know whether active Crohn's disease was present in the small bowel. It was not recommended in patients with chronic abdominal pain or diarrhea, in whom there was no evidence of abnormal biomarkers typically associated with Crohn's disease. CE was recommended to assess patients with celiac disease who have unexplained symptoms despite appropriate treatment, but not to make the diagnosis. In patients with overt gastrointestinal bleeding, and negative findings on esophagogastroduodenoscopy and colonoscopy, CE should be performed as soon as possible. CE was recommended only in selected patients with unexplained, mild, chronic iron-deficiency anemia. CE was suggested for surveillance in patients with polyposis syndromes or other small-bowel cancers, who required small-bowel studies. Colon capsule endoscopy should not be substituted routinely for colonoscopy. Patients should be made aware of the potential risks of CE including a failed procedure, capsule retention, or a missed lesion. Finally, standardized criteria for training and reporting in CE should be defined. Conclusions CE generally should be considered a complementary test in patients with gastrointestinal bleeding, Crohn's disease, or celiac disease, who have had negative or inconclusive endoscopic or imaging studies.","author":[{"dropping-particle":"","family":"Enns","given":"Robert A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hookey","given":"Lawrence","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Armstrong","given":"David","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bernstein","given":"Charles N.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Heitman","given":"Steven J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Teshima","given":"Christopher","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leontiadis","given":"Grigorios I.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tse","given":"Frances","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sadowski","given":"Daniel","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastroenterology","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2017","2"]]},"page":"497-514","publisher":"Elsevier","title":"Clinical Practice Guidelines for the Use of Video Capsule?Endoscopy","type":"article-journal","volume":"152"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>1</sup>","plainTextFormattedCitation":"1","previouslyFormattedCitation":"<sup>1</sup>"},"properties":{"noteIndex":0},"schema":""}1. A limitation of current WLI CE systems is the lack of interventional capability to manage small bowel lesions. By contrast, double-balloon enteroscopy (DBE), which relies on the use of a “push and pull” technique assisted by the alternate inflation and deflation of two distally located overtube balloons allowing thethat enables the endoscope to be advanced either in antegrade (i.e. oral introduction) or retrograde (i.e. anal introduction) manner, offers the opportunity to perform therapeutic interventions such as injection of hypertonic saline epinephrine adrenaline and argon plasma coagulationADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1053/j.gastro.2016.12.032","ISBN":"1528-0012 (Electronic) 0016-5085 (Linking)","ISSN":"00165085","PMID":"28063287","abstract":"Background & Aims Video capsule endoscopy (CE) provides a noninvasive option to assess the small intestine, but its use with respect to endoscopic procedures and cross-sectional imaging varies widely. The aim of this consensus was to provide guidance on the appropriate use of CE in clinical practice. Methods A systematic literature search identified studies on the use of CE in patients with Crohn's disease, celiac disease, gastrointestinal bleeding, and anemia. The quality of evidence and strength of recommendations were rated using the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Results The consensus includes 21 statements focused on the use of small-bowel CE and colon capsule endoscopy. CE was recommended for patients with suspected, known, or relapsed Crohn's disease when ileocolonoscopy and imaging studies were negative if it was imperative to know whether active Crohn's disease was present in the small bowel. It was not recommended in patients with chronic abdominal pain or diarrhea, in whom there was no evidence of abnormal biomarkers typically associated with Crohn's disease. CE was recommended to assess patients with celiac disease who have unexplained symptoms despite appropriate treatment, but not to make the diagnosis. In patients with overt gastrointestinal bleeding, and negative findings on esophagogastroduodenoscopy and colonoscopy, CE should be performed as soon as possible. CE was recommended only in selected patients with unexplained, mild, chronic iron-deficiency anemia. CE was suggested for surveillance in patients with polyposis syndromes or other small-bowel cancers, who required small-bowel studies. Colon capsule endoscopy should not be substituted routinely for colonoscopy. Patients should be made aware of the potential risks of CE including a failed procedure, capsule retention, or a missed lesion. Finally, standardized criteria for training and reporting in CE should be defined. Conclusions CE generally should be considered a complementary test in patients with gastrointestinal bleeding, Crohn's disease, or celiac disease, who have had negative or inconclusive endoscopic or imaging studies.","author":[{"dropping-particle":"","family":"Enns","given":"Robert A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hookey","given":"Lawrence","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Armstrong","given":"David","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bernstein","given":"Charles N.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Heitman","given":"Steven J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Teshima","given":"Christopher","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leontiadis","given":"Grigorios I.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tse","given":"Frances","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sadowski","given":"Daniel","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastroenterology","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2017","2"]]},"page":"497-514","publisher":"Elsevier","title":"Clinical Practice Guidelines for the Use of Video Capsule Endoscopy","type":"article-journal","volume":"152"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>6</sup>","plainTextFormattedCitation":"6","previouslyFormattedCitation":"<sup>6</sup>"},"properties":{"noteIndex":0},"schema":""}6. The use of DBE alone has a poorer diagnostic yield (diagnostic yieldDY 56%) than CE (DY diagnostic yield 62%), but a complementary strategy of DBE following positive CE has improved detection of OGIB (DY diagnostic yield 75%)ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/j.1440-1746.2010.06530.x","ISSN":"08159319","PMID":"21155884","abstract":"BACKGROUND AND AIM Uncertainty remains about the best test to evaluate patients with obscure gastrointestinal bleeding (OGIB). Previous meta-analyses demonstrated similar diagnostic yields with capsule endoscopy (CE) and double balloon enteroscopy (DBE) but relied primarily on data from abstracts and were not limited to bleeding patients. Many studies have since been published. Therefore, we performed a new meta-analysis comparing CE and DBE focused specifically on OGIB. METHODS A comprehensive literature search was performed of comparative studies using both CE and DBE in patients with OGIB. Data were extracted and analyzed to determine the weighted pooled diagnostic yields of each method and the odds ratio for the successful localization of a bleeding source. RESULTS Ten eligible studies were identified. The pooled diagnostic yield for CE was 62% (95% confidence interval [CI] 47.3-76.1) and for DBE was 56% (95% CI 48.9-62.1), with an odds ratio for CE compared with DBE of 1.39 (95% CI 0.88-2.20; P = 0.16). Subgroup analysis demonstrated the yield for DBE performed after a previously positive CE was 75.0% (95% CI 60.1-90.0), with the odds ratio for successful diagnosis with DBE after a positive CE compared with DBE in all patients of 1.79 (95% CI 1.09-2.96; P = 0.02). In contrast, the yield for DBE after a previously negative CE was only 27.5% (95% CI 16.7-37.8). CONCLUSIONS Capsule endoscopy and double balloon enteroscopy provide similar diagnostic yields in patients with OGIB. However, the diagnostic yield of DBE is significantly higher when performed in patients with a positive CE.","author":[{"dropping-particle":"","family":"Teshima","given":"Christopher W","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kuipers","given":"Ernst J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zanten","given":"Sander Veldhuyzen","non-dropping-particle":"van","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mensink","given":"Peter B F","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Gastroenterology and Hepatology","id":"ITEM-1","issue":"5","issued":{"date-parts":[["2011","5"]]},"page":"796-801","title":"Double balloon enteroscopy and capsule endoscopy for obscure gastrointestinal bleeding: An updated meta-analysis","type":"article-journal","volume":"26"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>12</sup>","plainTextFormattedCitation":"12","previouslyFormattedCitation":"<sup>12</sup>"},"properties":{"noteIndex":0},"schema":""}12 and improved outcomes in managing OGIB (reduced recurrent bleeding and requirement for blood transfusion)ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.gie.2007.02.044","ISSN":"00165107","PMID":"17643704","abstract":"BACKGROUND Obscure GI bleeding (OGIB) accounts for about 5% of all patients with GI bleeding. There are limited data on double-balloon enteroscopy (DBE) after a positive finding on capsule endoscopy (CE) in this setting. OBJECTIVE To determine the clinical outcomes after DBE therapy. DESIGN Prospective single-center cohort study. SETTING Tertiary referral university hospital. MAIN OUTCOME MEASUREMENTS Recurrent bleeding and blood transfusion requirements. PATIENTS AND METHODS This prospective study of 60 consecutive patients with OGIB was conducted between July 2004 and March 2006. Patients underwent CE before DBE to target the lesion for either further diagnostic evaluation or therapeutic intervention. The mean (standard deviation [SD]) duration of follow-up was 10.0 +/- 5.2 months. RESULTS The mean (SD) age was 62 +/- 18 years, with 31 men. A total of 74 DBE procedures were performed. An abnormality was seen by DBE in 45 patients (75%). In 12 patients (20%), a diagnosis was clarified or a new diagnosis was made. Therapy at DBE was performed in 34 patients (57%): 30 diathermies and 4 polypectomies. Endoscopic tattooing for targeted surgical removal was made in 3 additional patients. Multiple logistic regression analysis identified previous blood transfusion (odds ratio 10.5, 95% confidence interval 3.1-35; P < .001) to be the only independent predictor that required endoscopic therapy at DBE. Forty-eight patients (80%) had no further bleeding, and 46 patients (77%) had a normal Hb. Blood transfusion requirements fell from 34 patients to 10, P < .001. One patient had a perforation after therapeutic diathermy. LIMITATIONS Nonrandomized study. CONCLUSIONS In patients with OGIB and a positive finding on CE, DBE provided a safe and ambulatory method to achieve an excellent clinical outcome with significant reductions in recurrent bleeding and blood-transfusion requirements.","author":[{"dropping-particle":"","family":"Kaffes","given":"Arthur J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Siah","given":"Chiang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Koo","given":"Jenn H.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastrointestinal Endoscopy","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2007","8"]]},"page":"304-309","title":"Clinical outcomes after double-balloon enteroscopy in patients with obscure GI bleeding and a positive capsule endoscopy","type":"article-journal","volume":"66"},"uris":["",""]}],"mendeley":{"formattedCitation":"<sup>13</sup>","plainTextFormattedCitation":"13","previouslyFormattedCitation":"<sup>13</sup>"},"properties":{"noteIndex":0},"schema":""}13. Taken together, these findings suggest that performing DBE is a rational approach in patients with positive CE findings requiring biopsy or therapeutic interventionADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1159/000484218","ISSN":"0012-2823","PMID":"29393257","abstract":"BACKGROUND Obscure gastrointestinal bleeding (OGIB) is a common but embarrassing problem for gastroenterologists. Most bleeding lesions associated with OGIB are present in the small intestine and sometimes cannot be identified due to the difficulty associated with physical accessibility. Capsule endoscopy (CE) and double-balloon enteroscopy (DBE) have enabled in the process of diagnosing and have evolved to become approaches to treating OGIB. SUMMARY CE is a minimally invasive procedure and has a high diagnostic yield in patients with OGIB. DBE offers additional advantage of biopsy collection for pathological diagnosis and therapeutic intervention, but it should be noted that it sometimes causes severe adverse events such as acute pancreatitis, intestinal bleeding, and intestinal perforation. CE should be performed early in the workup course of OGIB. Positive CE findings enhance the diagnostic yield of subsequent DBE, and the effective therapeutic intervention improves the clinical outcomes of OGIB patients. On the contrary, there are no clear guidelines for further investigation of patients with negative CE findings at the present. Although patients in stable general condition may only require follow-up, repeated CE is useful to detect positive findings in patients with evidence of sustained bleeding and progressing anemia. We have revealed that repeated CE has higher positive finding rate than DBE in OGIB patients with negative CE findings in a preliminary study. Key Messages: CE and DBE have complementary roles in the management of OGIB, and the precise timing and proper sequence may be important for the approach to treating OGIB.","author":[{"dropping-particle":"","family":"Otani","given":"Koji","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Watanabe","given":"Toshio","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shimada","given":"Sunao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hosomi","given":"Shuhei","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nagami","given":"Yasuaki","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tanaka","given":"Fumio","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kamata","given":"Noriko","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Taira","given":"Koichi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yamagami","given":"Hirokazu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tanigawa","given":"Tetsuya","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shiba","given":"Masatsugu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fujiwara","given":"Yasuhiro","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Digestion","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2018"]]},"page":"52-58","title":"Clinical Utility of Capsule Endoscopy and Double-Balloon Enteroscopy in the Management of Obscure Gastrointestinal Bleeding","type":"article-journal","volume":"97"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>14</sup>","plainTextFormattedCitation":"14","previouslyFormattedCitation":"<sup>14</sup>"},"properties":{"noteIndex":0},"schema":""}14. Duodenal biopsy (showing villous atrophy) with EGD complemented by raised serological markers is essential for a definitive diagnosis of celiaccoeliac diseaseADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1136/gutjnl-2013-306578","ISBN":"1468-3288 (Electronic)\\r0017-5749 (Linking)","ISSN":"14683288","PMID":"24917550","abstract":"A multidisciplinary panel of 18 physicians and 3 non-physicians from eight countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA) reviewed the literature on diagnosis and management of adult coeliac disease (CD). This paper presents the recommendations of the British Society of Gastroenterology. Areas of controversies were explored through phone meetings and web surveys. Nine working groups examined the following areas of CD diagnosis and management: classification of CD; genetics and immunology; diagnostics; serology and endoscopy; follow-up; gluten-free diet; refractory CD and malignancies; quality of life; novel treatments; patient support; and screening for CD.","author":[{"dropping-particle":"","family":"Ludvigsson","given":"Jonas F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bai","given":"Julio C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Biagi","given":"Federico","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Card","given":"Timothy R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ciacci","given":"Carolina","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ciclitira","given":"Paul J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Green","given":"Peter H.R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hadjivassiliou","given":"Marios","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Holdoway","given":"Anne","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Heel","given":"David A.","non-dropping-particle":"Van","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kaukinen","given":"Katri","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leffler","given":"Daniel A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leonard","given":"Jonathan N.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lundin","given":"Knut E.A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"McGough","given":"Norma","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Davidson","given":"Mike","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Murray","given":"Joseph A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Swift","given":"Gillian L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Walker","given":"Marjorie M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zingone","given":"Fabiana","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sanders","given":"David S.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gut","id":"ITEM-1","issued":{"date-parts":[["2014"]]},"title":"Diagnosis and management of adult coeliac disease: Guidelines from the British society of gastroenterology","type":"article-journal"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>15</sup>","plainTextFormattedCitation":"15","previouslyFormattedCitation":"<sup>15</sup>"},"properties":{"noteIndex":0},"schema":""}15 . In patients contraindicated for EGD or declining the procedure but with positive celiaccoeliac serology and unremarkable findings on EGD, small bowel CE can be a useful diagnostic tool ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1186/1471-230X-12-90","ISSN":"1471-230X","abstract":"Video capsule endoscopy (VCE) is mainly used to evaluate patients with celiac disease in whom their course after diagnosis has been unfavorable and the diagnosis of adenocarcinoma, lymphoma or refractory celiac disease is entertained, but it has been suggested that VCE could replace esophagogastroduodenoscopy (EGD) and biopsy under certain circumstances. We report a single center case series of 8 patients with suspected celiac disease who were diagnosed by VCE. EGD and biopsy had been performed in 4 patients resulting in a negative biopsy, declined by 2, and contraindicated in 2 due to hemophilia and von Willebrand disease. In all patients, mucosal changes of scalloping, mucosal mosaicism and reduced folds were seen in either the duodenum or jejunum on VCE. Follow-up in 7 patients demonstrated improvement in either their serological abnormalities or their presenting clinical features on a gluten-free diet. Our case series demonstrates that VCE and the visualization of the characteristic mucosal changes of villous atrophy may replace biopsy as the mode of diagnosis when EGD is either declined or contraindicated, or when duodenal biopsies are negative and there remains a high index of suspicion. Further study is needed to clarify the role and cost of diagnosing celiac disease with VCE.","author":[{"dropping-particle":"","family":"Chang","given":"Matthew S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rubin","given":"Moshe","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lewis","given":"Suzanne K","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Green","given":"Peter H","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"BMC Gastroenterology","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2012","12"]]},"page":"90","publisher":"BioMed Central","title":"Diagnosing celiac disease by video capsule endoscopy (VCE) when esophogastroduodenoscopy (EGD) and biopsy is unable to provide a diagnosis: a case series","type":"article-journal","volume":"12"},"uris":["",""]}],"mendeley":{"formattedCitation":"<sup>16</sup>","plainTextFormattedCitation":"16","previouslyFormattedCitation":"<sup>16</sup>"},"properties":{"noteIndex":0},"schema":""}16. Small bowel CE allows forenables assessment offor complications associated with celiaccoeliac disease (such ase.g. intestinal T-cell lymphoma and, ulcerative jejunitis) and image magnification to identify patchy or distal areas of villous atrophy, which can be missed on standard upper digestive endoscopyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1055/s-2007-995361","ISSN":"0013-726X","author":[{"dropping-particle":"","family":"Hopper","given":"A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cross","given":"S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sanders","given":"D.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Endoscopy","id":"ITEM-1","issue":"03","issued":{"date-parts":[["2007","12","5"]]},"page":"219-224","title":"Patchy villous atrophy in adult patients with suspected gluten-sensitive enteropathy: is a multiple duodenal biopsy strategy appropriate?","type":"article-journal","volume":"40"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1038/ajg.2013.79","ISBN":"1572-0241","ISSN":"0002-9270","PMID":"23609613","abstract":"This guideline presents recommendations for the diagnosis and management of patients with celiac disease. Celiac disease is an immune-based reaction to dietary gluten (storage protein for wheat, barley, and rye) that primarily affects the small intestine in those with a genetic predisposition and resolves with exclusion of gluten from the diet. There has been a substantial increase in the prevalence of celiac disease over the last 50 years and an increase in the rate of diagnosis in the last 10 years. Celiac disease can present with many symptoms, including typical gastrointestinal symptoms (e.g., diarrhea, steatorrhea, weight loss, bloating, flatulence, abdominal pain) and also non-gastrointestinal abnormalities (e.g., abnormal liver function tests, iron deficiency anemia, bone disease, skin disorders, and many other protean manifestations). Indeed, many individuals with celiac disease may have no symptoms at all. Celiac disease is usually detected by serologic testing of celiac-specific antibodies. The diagnosis is confirmed by duodenal mucosal biopsies. Both serology and biopsy should be performed on a gluten-containing diet. The treatment for celiac disease is primarily a gluten-free diet (GFD), which requires significant patient education, motivation, and follow-up. Non-responsive celiac disease occurs frequently, particularly in those diagnosed in adulthood. Persistent or recurring symptoms should lead to a review of the patient's original diagnosis to exclude alternative diagnoses, a review of the GFD to ensure there is no obvious gluten contamination, and serologic testing to confirm adherence with the GFD. In addition, evaluation for disorders associated with celiac disease that could cause persistent symptoms, such as microscopic colitis, pancreatic exocrine dysfunction, and complications of celiac disease, such as enteropathy-associated lymphoma or refractory celiac disease, should be entertained. Newer therapeutic modalities are being studied in clinical trials, but are not yet approved for use in practice. Given the incomplete response of many patients to a GFD-free diet as well as the difficulty of adherence to the GFD over the long term, development of new effective therapies for symptom control and reversal of inflammation and organ damage are needed. The prevalence of celiac disease is increasing worldwide and many patients with celiac disease remain undiagnosed, highlighting the need for improved strategies in the future for the optima…","author":[{"dropping-particle":"","family":"Rubio-Tapia","given":"A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hill","given":"I D","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kelly","given":"C P","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Calderwood","given":"A H","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Murray","given":"J A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gastroenterology","given":"American College of","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"American Journal of Gastroenterology","id":"ITEM-2","issued":{"date-parts":[["2013"]]},"title":"ACG clinical guidelines: diagnosis and management of celiac disease","type":"article-journal"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>17,18</sup>","plainTextFormattedCitation":"17,18","previouslyFormattedCitation":"<sup>17,18</sup>"},"properties":{"noteIndex":0},"schema":""}17,18.Small bowel CE has consistently shown high sensitivity and specificity for the diagnosis of Crohn’s disease. In a meta-analysis including 428 patients, CE had a superior diagnostic yield than ileoscopy, small bowl radiography, CT enterography (CTE) and magnetic resonance enterography (MRE) in patients with suspected Crohn’s diseaseADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1038/ajg.2009.713","ISSN":"0002-9270","PMID":"20029412","abstract":"OBJECTIVES Capsule endoscopy (CE) has demonstrated superior performance compared with other modalities in its ability to detect early small-bowel (SB) Crohn's disease (CD), especially when ileoscopy is negative or unsuccessful. The aim of this study was to evaluate the diagnostic yield of CE compared with other modalities in patients with suspected and established CD using a meta-analysis. METHODS A thorough literature search for prospective studies comparing the diagnostic yield of CE with other modalities in patients with CD was undertaken. Other modalities included push enteroscopy (PE), colonoscopy with ileoscopy (C+IL), SB radiography (SBR), computed tomography enterography (CTE), and magnetic resonance enterography (MRE). Data on diagnostic yield among various modalities were extracted, pooled, and analyzed. Data on patients with suspected and established CD were analyzed separately. Weighted incremental yield (IYW) (diagnostic yield of CE-diagnostic yield of comparative modality) and 95% confidence intervals (CIs) of CE over comparative modalities were calculated. RESULTS A total of 12 trials (n=428) compared the yield of CE with SBR in patients with CD. Eight trials (n=236) compared CE with C+IL, four trials (n=119) compared CE with CTE, two trials (n=102) compared CE with PE, and four trials (n=123) compared CE with MRE. For the suspected CD subgroup, several comparisons met statistical significance. Yields in this subgroup were CE vs. SBR: 52 vs. 16% (IYw=32%, P<0.0001, 95% CI=16-48%), CE vs. CTE: 68 vs. 21% (IYw=47%, P<0.00001, 95% CI=31-63%), and CE vs. C+IL: 47 vs. 25% (IYw=22%, P=0.009, 95% CI=5-39%). Statistically significant yields for CE vs. an alternate diagnostic modality in established CD patients were seen in CE vs. PE: 66 vs. 9% (IYw=57%, P<0.00001, 95% CI=43-71%), CE vs. SBR: 71 vs. 36% (IYw=38%, P<0.00001, 95% CI=22-54%), and in CE vs. CTE: 71 vs. 39% (IYw=32%, P=or<0.0001, 95% CI=16-47%). CONCLUSIONS Our meta-analysis demonstrates that CE is superior to SBR, CTE, and C+IL in the evaluation of suspected CD patients. CE is also a more effective diagnostic tool in established CD patients compared with SBR, CTE, and PE.","author":[{"dropping-particle":"","family":"Dionisio","given":"Paula M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gurudu","given":"Suryakanth R","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leighton","given":"Jonathan A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leontiadis","given":"Grigoris I","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fleischer","given":"David E","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hara","given":"Amy K","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Heigh","given":"Russell I","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shiff","given":"Arthur D","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sharma","given":"Virender K","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"The American Journal of Gastroenterology","id":"ITEM-1","issue":"6","issued":{"date-parts":[["2010","6"]]},"page":"1240-1248","title":"Capsule Endoscopy Has a Significantly Higher Diagnostic Yield in Patients With Suspected and Established Small-Bowel Crohn's Disease: A Meta-Analysis","type":"article-journal","volume":"105"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>19</sup>","plainTextFormattedCitation":"19","previouslyFormattedCitation":"<sup>19</sup>"},"properties":{"noteIndex":0},"schema":""}19 . Mwith more recent studies quantifiedying the diagnostic yield of CE in patients with suspected Crohn’s disease to be 76.6% compared with in comparison to the 44.7% diagnostic yield of MRE for patients with suspected Crohn’s diseaseADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.cgh.2010.10.019","ISBN":"1542-3565","ISSN":"15423565","PMID":"21056692","abstract":"Background & Aims: Capsule endoscopy (CE) detects small bowel Crohn's disease with greater diagnostic yield than radiologic procedures, although there are concerns that CE has low specificity. We compared the sensitivity and specificity of CE, magnetic resonance imaging enterography (MRE) and computed tomography enterography (CTE) in patients with suspected or newly diagnosed Crohn's disease. Methods: We performed a prospective, blinded study of 93 patients scheduled to undergo ileocolonoscopy, MRE, and CTE and subsequently CE if stenosis was excluded. Physicians reporting CE, MRE, and CTE results were blinded to patient histories and findings from ileocolonoscopy and other small bowel examinations. Results were compared with those from ileoscopy (n = 70), ileoscopy and surgery (n = 4), or surgery (n = 1). Results: Twenty-one patients had Crohn's disease in the terminal ileum. The sensitivity and specificity for diagnosis of Crohn's disease of the terminal ileum were 100% and 91% by CE, 81% and 86% by MRE, and 76% and 85% by CTE, respectively. Proximal Crohn's disease was detected in 18 patients by using CE, compared with 2 and 6 patients by using MRE or CTE, respectively (P < 05). Small bowel stenosis was observed in 5 patients by using CTE and 1 patient by using MRE. Cross-sectional imaging results indicated additional stenoses in only 2 of the patients who received complete ileocolonoscopies. Conclusions: In suspected or newly diagnosed Crohn's disease, MRE and CTE have comparable sensitivities and specificities. In patients without endoscopic or clinical suspicion of stenosis, CE should be the first line modality for detection of small bowel Crohn's disease beyond the reach of the colonoscope. ? 2011 AGA Institute.","author":[{"dropping-particle":"","family":"Jensen","given":"Michael Dam","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nathan","given":"Torben","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rafaelsen","given":"S?ren Rafael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kjeldsen","given":"Jens","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Clinical Gastroenterology and Hepatology","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2011","2"]]},"page":"124-129.e1","title":"Diagnostic Accuracy of Capsule Endoscopy for Small Bowel Crohn's Disease Is Superior to That of MR Enterography or CT Enterography","type":"article-journal","volume":"9"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>20</sup>","plainTextFormattedCitation":"20","previouslyFormattedCitation":"<sup>20</sup>"},"properties":{"noteIndex":0},"schema":""}20,ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1093/ibd/izx107","ISSN":"1078-0998","PMID":"29506048","abstract":"Background and Aims Diagnostic yield of Small Bowel Capsule Endoscopy (SBCE) for the assessment of small bowel (SB) lesions is higher than radiologic imaging techniques. However, magnetic resonance enterography (MRE) data are scarce and inconclusive. Colon Capsule Endoscopy (CCE) is a new capsule modality. The primary aim of our study was to compare MRE and capsule endoscopy (CE) for the assessment of Crohn's disease (CD). The secondary objectives were to compare the diagnostic accuracy of both CE modalities and changes in Montreal classification after each examination. Methods We included 47 patients with established (n = 32) or suspected CD (n = 15). MRE was performed first to rule out strictures. In patients with a suspected stricture by MRE, an Agile Patency Capsule was performed. SB disease activity was measured by MaRIA score (MRE) and Lewis Index (CE). Results SB lesions were found in 36 of47 patients with CE and in 21 of47 patients with MRE (76.6% vs 44.7%, P = 0.001). Jejunal inflammation was detected by CE in 31.9% of patients and by MRE in 6.4% of patients (15/47 vs 3/47; P = 0.03); lesions in ileum were detected in 57.4% of patients by CE, and in 21.3% of patients by MRE (27/ 47 vs 10/ 47; P = 0.04). Finally, in terminal ileum, CE showed lesions in 68.1% (32/47) of patients, whereas MRE detected lesions in 38.3% (18/ 47 patients), (P = 0.001). The original Montreal classification was changed in 53.1% of patients (25/ 47) based on CE findings and in 12.7% of patients (6/47) based on MRE findings (P < 0.05). Conclusions In our cohort CE was significantly superior to MRE for detecting SB lesions, mainly superficial and proximal lesions. CE is useful for a appropriate patients' classification according to Montreal classification.","author":[{"dropping-particle":"","family":"González-Suárez","given":"Bego?a","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rodriguez","given":"Sonia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ricart","given":"Elena","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ordás","given":"Ingrid","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rimola","given":"Jordi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Díaz-González","given":"?lvaro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Romero","given":"Cristina","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Miguel","given":"Cristina Rodríguez","non-dropping-particle":"de","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jáuregui","given":"Arantxa","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Araujo","given":"Isis K","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ramirez","given":"Anna","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gallego","given":"Marta","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fernández-Esparrach","given":"Gloria","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ginés","given":"?ngels","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sendino","given":"Oriol","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Llach","given":"Josep","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Panés","given":"Julian","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Inflammatory Bowel Diseases","id":"ITEM-1","issue":"4","issued":{"date-parts":[["2018","3","19"]]},"page":"775-780","title":"Comparison of Capsule Endoscopy and Magnetic Resonance Enterography for the Assessment of Small Bowel Lesions in Crohn’s Disease","type":"article-journal","volume":"24"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>21</sup>","plainTextFormattedCitation":"21","previouslyFormattedCitation":"<sup>21</sup>"},"properties":{"noteIndex":0},"schema":""}21. In addition, although MRE allows forenables the investigation of transmural pathology, it is limited by increased examination time, poorer spatial resolution and increased costs compared with CEADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.crohns.2013.02.020","ISSN":"18739946","PMID":"23583097","abstract":"The management of patients with IBD requires evaluation with objective tools, both at the time of diagnosis and throughout the course of the disease, to determine the location, extension, activity and severity of inflammatory lesions, as well as, the potential existence of complications. Whereas endoscopy is a well-established and uniformly performed diagnostic examination, the implementation of radiologic techniques for assessment of IBD is still heterogeneous; variations in technical aspects and the degrees of experience and preferences exist across countries in Europe. ECCO and ESGAR scientific societies jointly elaborated a consensus to establish standards for imaging in IBD using magnetic resonance imaging, computed tomography, ultrasonography, and including also other radiologic procedures such as conventional radiology or nuclear medicine examinations for different clinical situations that include general principles, upper GI tract, colon and rectum, perineum, liver and biliary tract, emergency situation, and the postoperative setting. The statements and general recommendations of this consensus are based on the highest level of evidence available, but significant gaps remain in certain areas such as the comparison of diagnostic accuracy between different techniques, the value for therapeutic monitoring, and the prognostic implications of particular findings.","author":[{"dropping-particle":"","family":"Panes","given":"J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bouhnik","given":"Y.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Reinisch","given":"W.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stoker","given":"J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Taylor","given":"S.A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Baumgart","given":"D.C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Danese","given":"S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Halligan","given":"S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Marincek","given":"B.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Matos","given":"C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Peyrin-Biroulet","given":"L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rimola","given":"J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rogler","given":"G.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Assche","given":"G.","non-dropping-particle":"van","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ardizzone","given":"S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ba-Ssalamah","given":"A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bali","given":"M.A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bellini","given":"D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Biancone","given":"L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Castiglione","given":"F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ehehalt","given":"R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Grassi","given":"R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kucharzik","given":"T.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Maccioni","given":"F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Maconi","given":"G.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Magro","given":"F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Martín-Comín","given":"J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Morana","given":"G.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pendsé","given":"D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sebastian","given":"S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Signore","given":"A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tolan","given":"D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tielbeek","given":"J.A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Weishaupt","given":"D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wiarda","given":"B.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Laghi","given":"A.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Crohn's and Colitis","id":"ITEM-1","issue":"7","issued":{"date-parts":[["2013","8"]]},"page":"556-585","title":"Imaging techniques for assessment of inflammatory bowel disease: Joint ECCO and ESGAR evidence-based consensus guidelines","type":"article-journal","volume":"7"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>22</sup>","plainTextFormattedCitation":"22","previouslyFormattedCitation":"<sup>22</sup>"},"properties":{"noteIndex":0},"schema":""}22. CE can have an important role in monitoring Crohn’s disease activity and response to therapy, particularly with the availability of established disease activity scoring systems (for example the Capsule Endoscopy Crohn's Disease Activity Index, also known as the Niv score and the Lewis score)ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1097/MEG.0000000000000881","ISSN":"0954-691X","PMID":"28410352","abstract":"Capsule endoscopy (CE) may be used for the evaluation and follow-up of patients with Crohn's disease. CE scores correspond to the degree of mucosal inflammation, a major therapeutic target. The aim of this meta-analysis and systematic review was to determine whether mucosal healing assessment by CE may serve as a predictor of clinical remission in patients with Crohn's disease. To identify observational or controlled English-language full-text studies assessing mucosal healing by CE in patients with Crohn's disease up to 30 September 2016, we searched PubMed, Embase, Central, Medline, and Scopus using the key words 'mucosal healing' and 'capsule endoscopy'. A meta-analysis was carried out using 'Comprehensive meta-analysis' software. Pooled odds ratios and 95% confidence intervals were calculated. Five observational studies including 142 patients from five countries fulfilled the inclusion criteria. No publication bias was found by funnel plot. The mucosal healing CE score was found to be significantly associated with improved outcome after a follow-up of 12 weeks to 24 months, with an odds ratio of 11.06 (95% confidence interval: 3.74-32.73, P<0.001). The degree of heterogeneity among the studies was small (Q=2.014, d.f.[Q]=3, P=0.569 and I=0). Endoscopy scores may play a role in the long-term prognostic evaluation of patients with Crohn's disease. Our results may be accepted as proof of concept, but larger studies are needed to corroborate these findings.","author":[{"dropping-particle":"","family":"Niv","given":"Yaron","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"European Journal of Gastroenterology & Hepatology","id":"ITEM-1","issue":"7","issued":{"date-parts":[["2017","7"]]},"page":"844-848","title":"Small-bowel mucosal healing assessment by capsule endoscopy as a predictor of long-term clinical remission in patients with Crohn’s disease","type":"article-journal","volume":"29"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>23</sup>","plainTextFormattedCitation":"23","previouslyFormattedCitation":"<sup>23</sup>"},"properties":{"noteIndex":0},"schema":""}23. Inadequate ampulla of Vater (AoV) visualization, acting as a surrogate marker of segmental visualization of the duodenum, was identified as a limitation of axial CEADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/j.1751-2980.2012.00638.x","ISSN":"17512972","PMID":"23134524","abstract":"OBJECTIVE The aim of this study was to determine the detection rate of the ampulla of Vater (AoV) during small bowel capsule endoscopy (SBCE) examinations and compare the two SBCE systems used in our center. METHODS SBCE procedures performed in our center from March 2005 to June 2011 were reviewed retrospectively. A single reviewer, following a detailed protocol, analyzed 30 min of each recording to identify the AoV. RESULTS A total of 619 SBCE procedures were enrolled in the study, including 262 with a PillCam SB1, 148 with a PillCam SB2 and 209 with a MiroCam. AoV was identified in 59 SBCE examinations (9.5%), consisting of 28 with a PillCam SB1 (28/262, 10.7%), 13 with a PillCam SB2 (13/148, 8.8%) and 18 with a MiroCam (18/209, 8.6%) (P = 0.665). The AoV was visualized in 53.2 frames (median 12 frames, range 1-1056 frames); and the detection rate was low regardless of indication, patients' characteristics, SBCE system used or capsule transit parameters. Bile spout was associated with a higher AoV detection (P = 0.003). CONCLUSIONS The persistently low AoV detection rate using two different SBCE systems underlines the weakness of non-steerable capsule endoscopy. Furthermore, if AoV detection is taken as a surrogate marker of small polyp detection, it becomes obvious both that non-steerable SBCE cannot replace a side-viewing endoscope in the evaluation of periampullary polyps in familial adenomatous polyposis and that it is an infallible method in other small bowel polyposis states.","author":[{"dropping-particle":"","family":"Koulaouzidis","given":"Anastasios","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Plevris","given":"John N","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Digestive Diseases","id":"ITEM-1","issue":"12","issued":{"date-parts":[["2012","12"]]},"page":"621-627","title":"Detection of the ampulla of Vater in small bowel capsule endoscopy: Experience with two different systems","type":"article-journal","volume":"13"},"uris":["",""]}],"mendeley":{"formattedCitation":"<sup>24</sup>","plainTextFormattedCitation":"24","previouslyFormattedCitation":"<sup>24</sup>"},"properties":{"noteIndex":0},"schema":""}24. Improved detection of the ampulla of Vater was reported in a separate study that evaluated the use of a lateral-viewing CE platform, the CapsoCam Plus (CapsoVision, California, USA) (DYdiagnostic yield 70%) compared to axial-viewing CE (DYdiagnostic yield 10-44%),ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/jgh.12280","ISBN":"1440-1746 (Electronic)\\r0815-9319 (Linking)","ISSN":"08159319","PMID":"23701674","abstract":"BACKGROUND AND STUDY AIMS Capsule endoscopy is the first-line diagnostic technique for the small bowel. However, the inability to visualize the duodenal papilla is an inherent limitation of this method. In the present study, we evaluated feasibility of a newly developed CapsoCam SV1 capsule. PATIENTS AND METHODS This is a prospective dual center study of a newly developed video capsule CapsoCam SV1 from Capsovision, CA, providing panoramic 360° imaging. A high frequency of 20 frames occurs per second for the first 2 h and thereafter 12 frames/s, with a battery life of 15 h. We evaluated feasibility and completeness of small bowel examination together with secondary endpoints of duodenal papilla detection in 33 patients. Patients swallowed the capsules following colonoscopy or were prepared with 2 L of polyethylene glycol solution prior to the examination. All patients swallowed 20 mg of metoclopramide and 160 mg of simethicone 30 min before ingestion of the capsule. RESULTS Thirty-one of the 33 patients' data could be evaluated. Small bowel examination was complete in all procedures. Mean time to pass the small bowel was 258 ± 136 min. Average small bowel cleanliness was 3.3 ± 0.5. In 71% of the patients, we identified the duodenal papilla. No adverse reaction in relation to the capsule examination was observed. CONCLUSIONS CapsoCam SV1 is a safe and efficient tool in small bowel examination. The duodenal papilla as the only landmark in small bowel is detected in more than 70% of the patients.","author":[{"dropping-particle":"","family":"Friedrich","given":"Kilian","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gehrke","given":"Sven","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stremmel","given":"Wolfgang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sieg","given":"Andreas","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Gastroenterology and Hepatology (Australia)","id":"ITEM-1","issue":"9","issued":{"date-parts":[["2013","9"]]},"page":"1496-1501","title":"First clinical trial of a newly developed capsule endoscope with panoramic side view for small bowel: A pilot study","type":"article-journal","volume":"28"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>25</sup>","plainTextFormattedCitation":"25","previouslyFormattedCitation":"<sup>25</sup>"},"properties":{"noteIndex":0},"schema":""}25. In a prospective study of 20 patients with familial adenomatous polyposis (FAP) and Peutz-Jeghers syndrome (PJS), CE was superior to MRE in identifying polyps of < 5 mm diameterADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1155/2012/215028","ISSN":"1687-6121","abstract":"Objective . The objective of this study was to assess the utility of magnetic resonance enterography (MRE) compared with capsule endoscopy (CE) for the detection of small-bowel polyps in patients with familial adenomatous polyposis (FAP). Methods . Patients underwent MRE and CE. The polyps were classified according to size of polyp: <5 mm (small size), 5–10 mm (medium size), or >10 mm (large size). The location (jejunum or ileum) and the number of polyps (1–5, 6–20, >20) detected by CE were also assessed. MRE findings were compared with the results of CE. Results . Small-bowel polyps, were detected by CE in 4 of the 6 (66%) patients. Three patients had small-sized polyps and one patient had medium-sized polyps. CE detected polyps in four patients that, were not shown on MRE. Desmoid tumors were detected on anterior abdominal wall by MRE. Conclusion . In patients with FAP, CE can detect small-sized polyps in the small intestine not seen with MRE whereas MRE yields additional extraintestinal information.","author":[{"dropping-particle":"","family":"Akin","given":"E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Demirezer Bolat","given":"A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Buyukasik","given":"S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Algin","given":"O.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Selvi","given":"E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ersoy","given":"O.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastroenterology Research and Practice","id":"ITEM-1","issued":{"date-parts":[["2012","2"]]},"page":"1-5","publisher":"Hindawi","title":"Comparison between Capsule Endoscopy and Magnetic Resonance Enterography for the Detection of Polyps of the Small Intestine in Patients with Familial Adenomatous Polyposis","type":"article-journal","volume":"2012"},"uris":["",""]}],"mendeley":{"formattedCitation":"<sup>26</sup>","plainTextFormattedCitation":"26","previouslyFormattedCitation":"<sup>26</sup>"},"properties":{"noteIndex":0},"schema":""}26. CE is safe in patients who have undergone intestinal surgery and is recommended by the British Society of Gastroenterology every 1–3 years for the long-term surveillance of hereditary polyposis syndromes due to the increased risk of CRCADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/j.1572-0241.2005.41506.x","ISSN":"0002-9270","PMID":"15984971","abstract":"BACKGROUND Small intestinal (SI) surveillance is recommended for polyposis patients. The utility and safety of capsule endoscopy (CE) for surveillance of SI neoplasia in patients with familial adenomatous polyposis (FAP) and Peutz-Jeghers syndrome (PJS) is unknown. METHODS CE was offered to consecutive FAP and PJS patients due for routine upper endoscopic surveillance. The prevalence, location (jejunum, ileum), size (1-5 mm, 6-10 mm, >10 mm) and number (1-5, 6-12, >20) of polyps detected by CE was assessed. RESULTS 19 subjects (15 FAP/4 PJS) with a mean age of 43 were included. All subjects had previous intestinal surgery. No complications occurred with CE. CE in FAP: 9/15 (60%) of subjects with FAP had SI polyps. The prevalence of SI polyps was related to the duodenal polyposis stage and subject age. The location, size and number of polyps progressed as duodenal polyposis stage advanced. CE in PJS: 3/4 (75%) of subjects with PJS had SI polyps. The polyps were diffuse in 2/4 and only in the ileum in one subject. CE findings led to laparotomy with intra-operative endoscopic polypectomy in two PJS patients. CONCLUSION SI polyps are common in FAP but their importance is unknown. CE should be performed in FAP patients with stage III and IV duodenal disease. Clinically significant polyps are commonly detected by CE in PJS and lead to change in management in 50% of PJS subjects. CE should replace radiographic SI surveillance for PJS patients. CE is safe in polyposis patients who have undergone major intestinal surgery.","author":[{"dropping-particle":"","family":"Burke","given":"Carol A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Santisi","given":"Janice","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Church","given":"James","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Levinthal","given":"Gavin","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"The American Journal of Gastroenterology","id":"ITEM-1","issue":"7","issued":{"date-parts":[["2005","7"]]},"page":"1498-1502","title":"The Utility of Capsule Endoscopy Small Bowel Surveillance in Patients with Polyposis","type":"article-journal","volume":"100"},"uris":["",""]},{"id":"ITEM-2","itemData":{"DOI":"10.1136/gut.2009.179804","ISSN":"0017-5749","PMID":"20427401","abstract":"The British Society of Gastroenterology (BSG) and the Association of Coloproctology for Great Britain and Ireland (ACPGBI) commissioned this update of the 2002 guidance. The aim, as before, is to provide guidance on the appropriateness, method and frequency of screening for people at moderate and high risk from colorectal cancer. This guidance provides some new recommendations for those with inflammatory bowel disease and for those at moderate risk resulting from a family history of colorectal cancer. In other areas guidance is relatively unchanged, but the recent literature was reviewed and is included where appropriate.","author":[{"dropping-particle":"","family":"Cairns","given":"S. R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Scholefield","given":"J. H.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Steele","given":"R. J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dunlop","given":"M. G.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Thomas","given":"H. J. W.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Evans","given":"G. D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Eaden","given":"J. A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rutter","given":"M. D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Atkin","given":"W. P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Saunders","given":"B. P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lucassen","given":"A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jenkins","given":"P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fairclough","given":"P. D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Woodhouse","given":"C. R. J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gut","id":"ITEM-2","issue":"5","issued":{"date-parts":[["2010","5","1"]]},"page":"666-689","title":"Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002)","type":"article-journal","volume":"59"},"uris":["",""]}],"mendeley":{"formattedCitation":"<sup>27,28</sup>","plainTextFormattedCitation":"27,28","previouslyFormattedCitation":"<sup>27,28</sup>"},"properties":{"noteIndex":0},"schema":""}27,28. [H2]ColonThe wide lumen of the colon means that small bowel CE devices are more likely to move in a random manner, impairing high-quality image acquisition. Newer capsule endoscopes have been developed with double headed lenses, longer battery time and variable image capture rate with improved detection of colonic pathologyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1007/978-3-662-44062-9_3","author":[{"dropping-particle":"","family":"Kurniawan","given":"Niehls","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Keuchel","given":"Martin","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Video Capsule Endoscopy","id":"ITEM-1","issued":{"date-parts":[["2014"]]},"page":"15-20","publisher":"Springer Berlin Heidelberg","publisher-place":"Berlin, Heidelberg","title":"Technology","type":"chapter"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1007/978-3-662-44062-9_2","author":[{"dropping-particle":"","family":"McAlindon","given":"Mark E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hagenmüller","given":"Friedrich","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fleischer","given":"David E.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Video Capsule Endoscopy","id":"ITEM-2","issued":{"date-parts":[["2014"]]},"page":"5-13","publisher":"Springer Berlin Heidelberg","publisher-place":"Berlin, Heidelberg","title":"Fields of Application","type":"chapter"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>29,30</sup>","plainTextFormattedCitation":"29,30","previouslyFormattedCitation":"<sup>29,30</sup>"},"properties":{"noteIndex":0},"schema":""}29,30. In a meta-analysis of studies involving 1292 patients that compared the performance of second-generation colon CE device (COLON2; Medtronic, Minneapolis, USA) withto colonoscopy, it was found that COLON2 had a sensitivity and specificity of 86% and 88.1% respectively for detecting polyps >greater than 6mm, and detected all invasive cancers (n=11) identified on colonoscopyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.cgh.2016.04.038","ISSN":"15423565","PMID":"27165469","abstract":"BACKGROUND & AIMS Colon capsule endoscopy (CCE) is a noninvasive technique used to explore the colon without sedation or air insufflation. A second-generation capsule was recently developed to improve accuracy of detection, and clinical use has expanded globally. We performed a systematic review and meta-analysis to assess the accuracy of CCE in detecting colorectal polyps. METHODS We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and other databases from 1966 through 2015 for studies that compared accuracy of colonoscopy with histologic evaluation with CCE. The risk of bias within each study was ascertained according to Quality Assessment of Diagnostic Accuracy in Systematic Reviews recommendations. Per-patient accuracy values were calculated for polyps, overall and for first-generation (CCE-1) and second-generation (CCE-2) capsules. We analyzed data by using forest plots, the I2 statistic to calculate heterogeneity, and meta-regression analyses. RESULTS Fourteen studies provided data from 2420 patients (1128 for CCE-1 and 1292 for CCE-2). CCE-2 and CCE-1 detected polyps >6 mm with 86% sensitivity (95% confidence interval [CI], 82%-89%) and 58% sensitivity (95% CI, 44%-70%), respectively, and 88.1% specificity (95% CI, 74.2%-95.0%) and 85.7% specificity (95% CI, 80.2%-90.0%), respectively. CCE-2 and CCE-1 detected polyps >10 mm with 87% sensitivity (95% CI, 81%-91%) and 54% sensitivity (95% CI, 29%-77%), respectively, and 95.3% specificity (95% CI, 91.5%-97.5%) and 97.4% specificity (95% CI, 96.0%-98.3%), respectively. CCE-2 identified all 11 invasive cancers detected by colonoscopy. CONCLUSIONS The sensitivity in detection of polyps >6 mm and >10 mm increased substantially between development of first-generation and second-generation colon capsules. High specificity values for detection of polyps by CCE-2 seem to be achievable with a 10-mm cutoff and in a screening setting.","author":[{"dropping-particle":"","family":"Spada","given":"Cristiano","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pasha","given":"Shabana F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gross","given":"Seth A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leighton","given":"Jonathan A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schnoll-Sussman","given":"Felice","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Correale","given":"Loredana","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"González Suárez","given":"Bego?a","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Costamagna","given":"Guido","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hassan","given":"Cesare","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Clinical Gastroenterology and Hepatology","id":"ITEM-1","issue":"11","issued":{"date-parts":[["2016","11"]]},"page":"1533-1543.e8","title":"Accuracy of First- and Second-Generation Colon Capsules in Endoscopic Detection of Colorectal Polyps: A Systematic Review and Meta-analysis","type":"article-journal","volume":"14"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>31</sup>","plainTextFormattedCitation":"31","previouslyFormattedCitation":"<sup>31</sup>"},"properties":{"noteIndex":0},"schema":""}31. COLON 2 was found to havehad an equivalent performance to colonoscopy for larger polyps (>10mm) ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.cgh.2016.04.038","ISSN":"15423565","PMID":"27165469","abstract":"BACKGROUND & AIMS Colon capsule endoscopy (CCE) is a noninvasive technique used to explore the colon without sedation or air insufflation. A second-generation capsule was recently developed to improve accuracy of detection, and clinical use has expanded globally. We performed a systematic review and meta-analysis to assess the accuracy of CCE in detecting colorectal polyps. METHODS We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and other databases from 1966 through 2015 for studies that compared accuracy of colonoscopy with histologic evaluation with CCE. The risk of bias within each study was ascertained according to Quality Assessment of Diagnostic Accuracy in Systematic Reviews recommendations. Per-patient accuracy values were calculated for polyps, overall and for first-generation (CCE-1) and second-generation (CCE-2) capsules. We analyzed data by using forest plots, the I2 statistic to calculate heterogeneity, and meta-regression analyses. RESULTS Fourteen studies provided data from 2420 patients (1128 for CCE-1 and 1292 for CCE-2). CCE-2 and CCE-1 detected polyps >6 mm with 86% sensitivity (95% confidence interval [CI], 82%-89%) and 58% sensitivity (95% CI, 44%-70%), respectively, and 88.1% specificity (95% CI, 74.2%-95.0%) and 85.7% specificity (95% CI, 80.2%-90.0%), respectively. CCE-2 and CCE-1 detected polyps >10 mm with 87% sensitivity (95% CI, 81%-91%) and 54% sensitivity (95% CI, 29%-77%), respectively, and 95.3% specificity (95% CI, 91.5%-97.5%) and 97.4% specificity (95% CI, 96.0%-98.3%), respectively. CCE-2 identified all 11 invasive cancers detected by colonoscopy. CONCLUSIONS The sensitivity in detection of polyps >6 mm and >10 mm increased substantially between development of first-generation and second-generation colon capsules. High specificity values for detection of polyps by CCE-2 seem to be achievable with a 10-mm cutoff and in a screening setting.","author":[{"dropping-particle":"","family":"Spada","given":"Cristiano","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pasha","given":"Shabana F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gross","given":"Seth A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leighton","given":"Jonathan A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schnoll-Sussman","given":"Felice","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Correale","given":"Loredana","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"González Suárez","given":"Bego?a","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Costamagna","given":"Guido","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hassan","given":"Cesare","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Clinical Gastroenterology and Hepatology","id":"ITEM-1","issue":"11","issued":{"date-parts":[["2016","11"]]},"page":"1533-1543.e8","title":"Accuracy of First- and Second-Generation Colon Capsules in Endoscopic Detection of Colorectal Polyps: A Systematic Review and Meta-analysis","type":"article-journal","volume":"14"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>31</sup>","plainTextFormattedCitation":"31","previouslyFormattedCitation":"<sup>31</sup>"},"properties":{"noteIndex":0},"schema":""}31, a confounding factor is adequacy of bowel preparationADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.cgh.2016.04.038","ISSN":"15423565","PMID":"27165469","abstract":"BACKGROUND & AIMS Colon capsule endoscopy (CCE) is a noninvasive technique used to explore the colon without sedation or air insufflation. A second-generation capsule was recently developed to improve accuracy of detection, and clinical use has expanded globally. We performed a systematic review and meta-analysis to assess the accuracy of CCE in detecting colorectal polyps. METHODS We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and other databases from 1966 through 2015 for studies that compared accuracy of colonoscopy with histologic evaluation with CCE. The risk of bias within each study was ascertained according to Quality Assessment of Diagnostic Accuracy in Systematic Reviews recommendations. Per-patient accuracy values were calculated for polyps, overall and for first-generation (CCE-1) and second-generation (CCE-2) capsules. We analyzed data by using forest plots, the I2 statistic to calculate heterogeneity, and meta-regression analyses. RESULTS Fourteen studies provided data from 2420 patients (1128 for CCE-1 and 1292 for CCE-2). CCE-2 and CCE-1 detected polyps >6 mm with 86% sensitivity (95% confidence interval [CI], 82%-89%) and 58% sensitivity (95% CI, 44%-70%), respectively, and 88.1% specificity (95% CI, 74.2%-95.0%) and 85.7% specificity (95% CI, 80.2%-90.0%), respectively. CCE-2 and CCE-1 detected polyps >10 mm with 87% sensitivity (95% CI, 81%-91%) and 54% sensitivity (95% CI, 29%-77%), respectively, and 95.3% specificity (95% CI, 91.5%-97.5%) and 97.4% specificity (95% CI, 96.0%-98.3%), respectively. CCE-2 identified all 11 invasive cancers detected by colonoscopy. CONCLUSIONS The sensitivity in detection of polyps >6 mm and >10 mm increased substantially between development of first-generation and second-generation colon capsules. High specificity values for detection of polyps by CCE-2 seem to be achievable with a 10-mm cutoff and in a screening setting.","author":[{"dropping-particle":"","family":"Spada","given":"Cristiano","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pasha","given":"Shabana F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gross","given":"Seth A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leighton","given":"Jonathan A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schnoll-Sussman","given":"Felice","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Correale","given":"Loredana","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"González Suárez","given":"Bego?a","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Costamagna","given":"Guido","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hassan","given":"Cesare","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Clinical Gastroenterology and Hepatology","id":"ITEM-1","issue":"11","issued":{"date-parts":[["2016","11"]]},"page":"1533-1543.e8","title":"Accuracy of First- and Second-Generation Colon Capsules in Endoscopic Detection of Colorectal Polyps: A Systematic Review and Meta-analysis","type":"article-journal","volume":"14"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>31</sup>","plainTextFormattedCitation":"31","previouslyFormattedCitation":"<sup>31</sup>"},"properties":{"noteIndex":0},"schema":""}31. Specific regimes for optimum bowel cleansing have are being developed but they are more vigorous than those used in conventional colonoscopy, thus potentially limiting acceptability by patients. For all the above reasons, colonic capsule endoscopyCE can be considered if colonoscopy is not complete, the procedure is contraindicated or if patients are unwilling to undergo the procedure ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1053/j.gastro.2016.12.032","ISBN":"1528-0012 (Electronic) 0016-5085 (Linking)","ISSN":"00165085","PMID":"28063287","abstract":"Background & Aims Video capsule endoscopy (CE) provides a noninvasive option to assess the small intestine, but its use with respect to endoscopic procedures and cross-sectional imaging varies widely. The aim of this consensus was to provide guidance on the appropriate use of CE in clinical practice. Methods A systematic literature search identified studies on the use of CE in patients with Crohn's disease, celiac disease, gastrointestinal bleeding, and anemia. The quality of evidence and strength of recommendations were rated using the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Results The consensus includes 21 statements focused on the use of small-bowel CE and colon capsule endoscopy. CE was recommended for patients with suspected, known, or relapsed Crohn's disease when ileocolonoscopy and imaging studies were negative if it was imperative to know whether active Crohn's disease was present in the small bowel. It was not recommended in patients with chronic abdominal pain or diarrhea, in whom there was no evidence of abnormal biomarkers typically associated with Crohn's disease. CE was recommended to assess patients with celiac disease who have unexplained symptoms despite appropriate treatment, but not to make the diagnosis. In patients with overt gastrointestinal bleeding, and negative findings on esophagogastroduodenoscopy and colonoscopy, CE should be performed as soon as possible. CE was recommended only in selected patients with unexplained, mild, chronic iron-deficiency anemia. CE was suggested for surveillance in patients with polyposis syndromes or other small-bowel cancers, who required small-bowel studies. Colon capsule endoscopy should not be substituted routinely for colonoscopy. Patients should be made aware of the potential risks of CE including a failed procedure, capsule retention, or a missed lesion. Finally, standardized criteria for training and reporting in CE should be defined. Conclusions CE generally should be considered a complementary test in patients with gastrointestinal bleeding, Crohn's disease, or celiac disease, who have had negative or inconclusive endoscopic or imaging studies.","author":[{"dropping-particle":"","family":"Enns","given":"Robert A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hookey","given":"Lawrence","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Armstrong","given":"David","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bernstein","given":"Charles N.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Heitman","given":"Steven J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Teshima","given":"Christopher","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leontiadis","given":"Grigorios I.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tse","given":"Frances","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sadowski","given":"Daniel","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastroenterology","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2017","2"]]},"page":"497-514","publisher":"Elsevier","title":"Clinical Practice Guidelines for the Use of Video Capsule?Endoscopy","type":"article-journal","volume":"152"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>1</sup>","plainTextFormattedCitation":"1","previouslyFormattedCitation":"<sup>1</sup>"},"properties":{"noteIndex":0},"schema":""}1.[H2]EsophagusOesophagusThe PillCam ESO (Medtronic, Minneapolis, USA), developed in 2004, is the only WLI CE system licensed for examining the esophagusoesophagus. The capsule is equipped with a camera at both ends to improve detection of oesophagealoesophageal pathology, in contrast to the single camera CE systems used for the small bowel. OeEsophageal CE is increasingly considered as a potentially useful alternative investigative modality to EGD, given that EGD is more uncomfortable for the patient and more labour intensive to performADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1055/s-2005-870311","ISSN":"0013-726X","PMID":"16189791","author":[{"dropping-particle":"","family":"Sharma","given":"V. K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Eliakim","given":"R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sharma","given":"P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Faigel","given":"D.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Endoscopy","id":"ITEM-1","issue":"10","issued":{"date-parts":[["2005","10"]]},"page":"1060-1064","title":"ICCE Consensus for Esophageal Capsule Endoscopy","type":"article-journal","volume":"37"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>32</sup>","plainTextFormattedCitation":"32","previouslyFormattedCitation":"<sup>32</sup>"},"properties":{"noteIndex":0},"schema":""}32,ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1097/01.mcg.0000170764.29202.24","ISBN":"0192-0790 (Print)\\r0192-0790 (Linking)","ISSN":"0192-0790","PMID":"16000923","abstract":"INTRODUCTION: Endoscopy is commonly performed to evaluate for suspected or established esophageal diseases including gastroesophageal reflux disease (GERD) and its complications. The newly developed PillCam ESO Esophageal Capsule offers an alternative approach to visualize the esophagus and to evaluate patients with suspected esophageal disease.\\n\\nAIM: Compare the accuracy (specificity, sensitivity, positive predictive value [PPV], and negative predictive value [NPV]) of esophageal capsule endoscopy (ECE) compared with esophagogastroduodenoscopy (EGD) in evaluating patients with GERD.\\n\\nMETHODS: A multicenter pivotal trial was conducted at seven sites. The PillCam ESO esophageal capsule is similar to the standard capsule endoscope used for the small bowel but acquires video images from both ends of the device at 2 frames/second/end. A total of 106 patients (93 GERD; 13 Barrett) underwent ECE followed by EGD. ECE videos were evaluated by an investigator blinded to EGD findings. A blinded adjudication committee reviewed all discrepant findings between ECE and EGD.\\n\\nRESULTS: Sixty-six of 106 patients had positive esophageal findings, ECE identified esophageal abnormalities in 61 (sensitivity, 92%; specificity, 95%). The per-protocol sensitivity, specificity, PPV, and NPV of ECE for Barrett esophagus were 97%, 99%, 97%, and 99%, respectively, and for esophagitis 89%, 99%, 97%, and 94%, respectively. ECE was preferred over EGD by all patients. There were no adverse events related to ECE.\\n\\nCONCLUSIONS: ECE is a convenient and sensitive method for visualization of esophageal mucosal pathology and may provide an effective method to evaluate patients for esophageal disease.","author":[{"dropping-particle":"","family":"Eliakim","given":"Rami","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sharma","given":"Virender K","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yassin","given":"Kamel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Adler","given":"Samuel N","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jacob","given":"Harold","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cave","given":"David R","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sachdev","given":"Ritu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mitty","given":"Roger D","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hartmann","given":"Dirk","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schilling","given":"Dieter","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Riemann","given":"Jurgen F","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bar-Meir","given":"Simon","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bardan","given":"Eytan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fennerty","given":"Brian","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Eisen","given":"Glenn","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Faigel","given":"Douglas","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lewis","given":"Blair S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fleischer","given":"David E","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Clinical Gastroenterology","id":"ITEM-1","issue":"7","issued":{"date-parts":[["2005","8"]]},"page":"572-578","title":"A Prospective Study of the Diagnostic Accuracy of PillCam ESO Esophageal Capsule Endoscopy Versus Conventional Upper Endoscopy in Patients With Chronic Gastroesophageal Reflux Diseases","type":"article-journal","volume":"39"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>33</sup>","plainTextFormattedCitation":"33","previouslyFormattedCitation":"<sup>33</sup>"},"properties":{"noteIndex":0},"schema":""}33. However, currently EGD remains the superior diagnostic tool for the detection of esophagealoesophageal pathology (e.g. Barret’sBarrett esophagusoesophagus, oesophagealoesophageal varices)ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.5946/ce.2018.101","ISSN":"2234-2400","author":[{"dropping-particle":"","family":"Park","given":"Junseok","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cho","given":"Young Kwan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kim","given":"Ji Hyun","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Clinical Endoscopy","id":"ITEM-1","issue":"4","issued":{"date-parts":[["2018","7","31"]]},"page":"317-322","title":"Current and Future Use of Esophageal Capsule Endoscopy","type":"article-journal","volume":"51"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>34</sup>","plainTextFormattedCitation":"34","previouslyFormattedCitation":"<sup>34</sup>"},"properties":{"noteIndex":0},"schema":""}34.[H1]Limitations of capsule endoscopyAs shown in Table 1, the differences between available WLI capsules lie mainly with the number of imaging devices, the frame rate and battery life. Typically, these battery-powered WLI capsules consist of one or more imagers (typically with a resolution of 320?×?240?pixels ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1186/s12938-015-0108-3","ISSN":"1475-925X","PMID":"26626725","abstract":"The paper presents an overview of endoscopic capsules with particular emphasis on technical aspects. It indicates common problems in capsule endoscopy such as: (1) limited wireless communication (2) the use of capsule endoscopy in the case of partial patency of the gastrointestinal tract, (3) limited imaging area, (4) external capsule control limitations. It also presents the prospects of capsule endoscopy, the most recent technical solutions for biopsy and the mobility of the capsule in the gastrointestinal tract. The paper shows the possibilities of increasing clinical usefulness of capsule endoscopy resulting from technological limitations. Attention has also been paid to the current role of capsule endoscopy in screening tests and the limitations of its effectiveness. The paper includes the author's recommendations concerning the direction of further research and the possibility of enhancing the scope of capsule endoscopy.","author":[{"dropping-particle":"","family":"Koprowski","given":"Robert","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Biomedical engineering online","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2015"]]},"page":"111","publisher":"BioMed Central","title":"Overview of technical solutions and assessment of clinical usefulness of capsule endoscopy.","type":"article-journal","volume":"14"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>35</sup>","plainTextFormattedCitation":"35","previouslyFormattedCitation":"<sup>35</sup>"},"properties":{"noteIndex":0},"schema":""}35), 4–6 light emitting diodes (LEDs) to provide illumination, an onboard microprocessor, and a telemetry system for transmitting images to an external receiver attached to a data logger that is worn by the patient. Although the imaging resolution of CE is less than the high-definition resolution possible with conventional endoscopy owing to the constraints of miniaturization, numerous studies have demonstrated good diagnostic yield of various CE devices within the small bowel for the detection of OGIB, iron deficiency anemia and celiaccoeliac diseaseADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1586/egh.13.20","ISSN":"1747-4124","author":[{"dropping-particle":"","family":"Mustafa","given":"Barzin F","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Samaan","given":"Mark","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Langmead","given":"Louise","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Khasraw","given":"Mustafa","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Expert Review of Gastroenterology & Hepatology","id":"ITEM-1","issue":"4","issued":{"date-parts":[["2013","5","10"]]},"page":"323-329","title":"Small bowel video capsule endoscopy: an overview","type":"article-journal","volume":"7"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1136/fg.2009.000463","ISSN":"2041-4137","author":[{"dropping-particle":"","family":"McAlindon","given":"M. E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sanders","given":"D. S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sidhu","given":"R.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Frontline Gastroenterology","id":"ITEM-2","issue":"2","issued":{"date-parts":[["2010","7","1"]]},"page":"82-87","title":"Capsule endoscopy: 10 years on and in the frontline","type":"article-journal","volume":"1"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>36,37</sup>","plainTextFormattedCitation":"36,37","previouslyFormattedCitation":"<sup>36,37</sup>"},"properties":{"noteIndex":0},"schema":""}36,37. However, the small number of comparative studies conducted so far have shown no meaningful advantage of one type of WLI CE over anotherADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.5754/hge10472","ISSN":"0172-6390","PMID":"22469721","abstract":"BACKGROUND/AIMS Although capsule endoscopy (CE) is widely used to evaluate small bowel diseases, its diagnostic power has not been firmly established. The aim of this study was to compare the abilities of the \"Miro- Cam\" and \"PillCam SB\" to detect Z-line and duodenal papillae. METHODOLOGY The records of 141 patients who had CE studies between January 2004 and December 2008 were retrospectively reviewed by two gastroenterologists. All patients had undergone esophagogastroduodenoscopy. The primary endpoint of the present study was the detection rate of Z-line and duodenal papillae. RESULTS Among the 141 patients, 84 (60%) received CE using the PillCam SB and 57 (40%) using the MiroCam. There were no statistical differences in the baseline characteristics of the patients between the two groups. The Z-line detection rate was 36.9% with the PillCam SB and 47.7% with the MiroCam (p=0.227). The detection rate of duodenal papillae was 13.1% with the PillCam SB and 29.8% with the MiroCam (p=0.018). CONCLUSIONS While the devices were similar for visualizing the Z-line, the MiroCam showed a higher diagnostic yield for detecting duodenal papillae than did the PillCam SB. The sensitivities of both for visualizing duodenal papillae were still limited, however.","author":[{"dropping-particle":"","family":"Hong","given":"Sung Pil","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cheon","given":"Jae Hee","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"Il","family":"Kim","given":"Tae","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Song","given":"Si Young","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kim","given":"Won Ho","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Hepato-gastroenterology","id":"ITEM-1","issue":"115","issued":{"date-parts":[["2012","5"]]},"page":"778-81","title":"Comparison of the diagnostic yield of \"MiroCam\" and \"PillCam SB\" capsule endoscopy.","type":"article-journal","volume":"59"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1055/s-2007-966943","ISSN":"1438-8812","PMID":"18072053","abstract":"BACKGROUND AND STUDY AIMS Capsule endoscopy is an established technique in the evaluation of obscure gastrointestinal bleeding. The primary aim of the study is to compare the diagnostic yield of the two different capsule endoscopes. PATIENTS AND METHODS Patients with signs of mid-gastrointestinal bleeding after negative upper endoscopy and colonoscopy studies were included. Patients were randomized to undergo two capsule endoscopies using different capsule endoscopes (Given Pillcam SB and Olympus EndoCapsule) in random order. RESULTS Forty patients (18 women, 22 men) were included in the study. All EndoCapsules reached the colon within the mean recording time of 591 +/- 52 minutes, whereas 33 out of 40 PillCam SB reached the colon within the mean recording time of 471 +/- 27 minutes. Lesions were detected in 31 patients: with both devices in 24, only by PillCam SB in 2, and, conversely, only by EndoCapsule in 5 (not significant). With regard to lesions with high bleeding potential (P2 lesions), PillCam SB detected them in 22 patients, EndoCapsule in 25 patients (not significant). In all four cases of intestinal P2 lesions that were not detected by the PillCam SB but were detected by the EndoCapsule, the PillCam SB had not reached the cecum. CONCLUSION In this study there was a statistically nonsignificant trend for the EndoCapsule to detect more bleeding sources in patients with suspected small bowel bleeding than did the PillCam SB, which may have been due to the longer recording times with the currently available EndoCapsule.","author":[{"dropping-particle":"","family":"Hartmann","given":"D","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Eickhoff","given":"A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Damian","given":"U","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Riemann","given":"J F","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Endoscopy","id":"ITEM-2","issue":"12","issued":{"date-parts":[["2007","12"]]},"page":"1041-5","title":"Diagnosis of small-bowel pathology using paired capsule endoscopy with two different devices: a randomized study.","type":"article-journal","volume":"39"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.5009/gnl.2010.4.2.192","ISSN":"2005-1212","PMID":"20559521","abstract":"BACKGROUND/AIMS Studies have investigated the use of different types of radiofrequency capsules for comparison or sequential capsule endoscopy, but none have compared the MiroCam device - which utilizes a novel data transmission technology - with other capsules. This study compared the feasibility of sequential capsule endoscopy using the MiroCam and PillCam SB devices, which employ different transmission technologies. METHODS Patients with diseases requiring capsule endoscopy were enrolled. After a 12-hour fast, one randomly selected capsule was swallowed. The second capsule was swallowed once fluoroscopy had indicated that the first capsule had migrated below the gastric outlet. RESULTS The total operating time in 24 patients was 702+/-60 min (mean+/-SD) for the MiroCam and 446+/-28 min for the PillCam SB (p<0.0001). The rate of a complete examination to the cecum was 83.3% for the MiroCam and 58.3% for the PillCam SB (p=0.031). Diagnostic yields for the MiroCam, PillCam SB, and sequential capsule endoscopy were 45.8%, 41.7%, and 50.0%, respectively. The agreement rate between the two capsules was 87.5%, with a kappa value of 0.74. Electrical interference in data transmission between the two capsules was not observed, but temporary visual interferences were observed in seven patients (29.2%). CONCLUSIONS Sequential capsule endoscopy with the MiroCam and PillCam SB produced slight but nonsignificant increases in the diagnostic yield, and the two capsules did not exhibit electrical interference. A larger trial is necessary for elucidating the usefulness of sequential capsule endoscopy.","author":[{"dropping-particle":"","family":"Kim","given":"Hee Man","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kim","given":"Yoon Jae","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kim","given":"Hong Jeong","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Park","given":"Semi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Park","given":"Jeong Youp","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shin","given":"Sung Kwan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cheon","given":"Jae Hee","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lee","given":"Sang Kil","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lee","given":"Yong Chan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Park","given":"Seung Woo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bang","given":"Seungmin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Song","given":"Si Young","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gut and liver","id":"ITEM-3","issue":"2","issued":{"date-parts":[["2010","6"]]},"page":"192-200","title":"A Pilot Study of Sequential Capsule Endoscopy Using MiroCam and PillCam SB Devices with Different Transmission Technologies.","type":"article-journal","volume":"4"},"uris":[""]},{"id":"ITEM-4","itemData":{"DOI":"10.3748/wjg.v21.i18.5542","ISSN":"2219-2840","PMID":"25987777","abstract":"AIM To evaluate the completion rate and diagnostic yield of the PillCam SB2-ex in comparison to the PillCam SB2. METHODS Two hundred cases using the 8-h PillCam SB2 were retrospectively compared to 200 cases using the 12 h PillCam SB2-ex at a tertiary academic center. Endoscopically placed capsules were excluded from the study. Demographic information, indications for capsule endoscopy, capsule type, study length, completion of exam, clinically significant findings, timestamp of most distant finding, and significant findings beyond 8 h were recorded. RESULTS The 8 and 12 h capsule groups were well matched respectively for both age (70.90 ± 14.19 vs 71.93 ± 13.80, P = 0.46) and gender (45.5% vs 48% male, P = 0.69). The most common indications for the procedure in both groups were anemia and obscure gastrointestinal bleeding. PillCam SB2-ex had a significantly higher completion rate than PillCam SB2 (88% vs 79.5%, P = 0.03). Overall, the diagnostic yield was greater for the 8 h capsule (48.5% for SB2 vs 35% for SB2-ex, P = 0.01). In 4/70 (5.7%) of abnormal SB2-ex exams the clinically significant finding was noted in the small bowel beyond the 8 h mark. CONCLUSION In our study, we found the PillCam SB2-ex to have a significantly increased completion rate, though without any improvement in diagnostic yield compared to the PillCam SB2.","author":[{"dropping-particle":"","family":"Rahman","given":"Merajur","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Akerman","given":"Stuart","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"DeVito","given":"Bethany","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Miller","given":"Larry","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Akerman","given":"Meredith","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sultan","given":"Keith","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"World journal of gastroenterology","id":"ITEM-4","issue":"18","issued":{"date-parts":[["2015","5","14"]]},"page":"5542-7","title":"Comparison of the diagnostic yield and outcomes between standard 8 h capsule endoscopy and the new 12 h capsule endoscopy for investigating small bowel pathology.","type":"article-journal","volume":"21"},"uris":[""]},{"id":"ITEM-5","itemData":{"DOI":"10.3748/wjg.v21.i9.2677","ISSN":"2219-2840","PMID":"25759536","abstract":"AIM To determine if longer battery life improves capsule endoscopy (CE) completion rates. METHODS A retrospective study was performed at a tertiary, university-affiliated hospital in Vancouver, Canada. Patients who underwent CE with either PillCam? SB2 or SB2U between 01/2010 and 12/2013 were considered for inclusion. SB2 and SB2U share identical physical dimensions but differ in their battery lives (8 h vs 12 h). Exclusion criteria included history of gastric or small bowel surgery, endoscopic placement of CE, interrupted view of major landmarks due to technical difficulty or significant amount of debris, and repeat CE using same system. Basic demographics, comorbidities, medications, baseline bowel habits, and previous surgeries were reviewed. Timing of major landmarks in CE were recorded, and used to calculate gastric transit time, small bowel transit time, and total recording time. A complete CE study was defined as visualization of cecum. Transit times and completion rates were compared. RESULTS Four hundred and eight patients, including 208 (51.0%) males, were included for analysis. The mean age was 55.5 ± 19.3 years. The most common indication for CE was gastrointestinal bleeding (n = 254, 62.3%), followed by inflammatory bowel disease (n = 86, 21.1%). There was no difference in gastric transit times (group difference 0.90, 95%CI: 0.72-1.13, P = 0.352) and small bowel transit times (group difference 1.07, 95%CI: 0.95-1.19, P = 0.261) between SB2U and SB2, but total recording time was about 14% longer in the SB2U group (95%CI: 10%-18%, P < 0.001) and there was a corresponding trend toward higher completion rate (88.2% vs 93.2%, OR = 1.78, 95%CI 0.88-3.63, P = 0.111). There was no statistically significant difference in the rates of positive findings (OR = 0.98, 95%CI: 0.64-1.51, P = 0.918). CONCLUSION Extending the operating time of CE may be a simple method to improve completion rate although it does not affect the rate of positive findings.","author":[{"dropping-particle":"","family":"Ou","given":"George","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shahidi","given":"Neal","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Galorport","given":"Cherry","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Takach","given":"Oliver","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lee","given":"Terry","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Enns","given":"Robert","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"World journal of gastroenterology","id":"ITEM-5","issue":"9","issued":{"date-parts":[["2015","3","7"]]},"page":"2677-82","title":"Effect of longer battery life on small bowel capsule endoscopy.","type":"article-journal","volume":"21"},"uris":[""]},{"id":"ITEM-6","itemData":{"DOI":"10.1016/j.gie.2007.12.037","ISSN":"1097-6779","PMID":"18410941","abstract":"BACKGROUND Video capsule endoscopy has been shown to be the single most effective endoscopic procedure for identifying the source of obscure GI bleeding (OGIB). OBJECTIVE Our purpose was to report on the Food and Drug Administration pivotal trial in which the Endocapsule (EC) (Olympus America, Allentown, Pa) was compared with the Pillcam SB (PSB) (Given Imaging, Yoqneam, Israel) in patients with OGIB. DESIGN A novel trial design was used in which the EC and the PSB were swallowed by the same patient 40 minutes apart, in randomized order. SETTING Four academic medical centers. PATIENTS Patients with OGIB aged 18 to 85 years who had either been transfused or who had a hematocrit of <31% in males or <28% in females. INTERVENTIONS Both video capsules were swallowed in random order. Videos from the PSB were read locally for patient management. All videos were then read by at least 2 independent readers for normal versus abnormal categorization, a diagnosis, capsule transit time, reading time, and a subjective assessment of image quality. MAIN OUTCOME MEASUREMENT Categorization of videos as either normal or abnormal. RESULTS Data from 51 of 63 enrolled patients were analyzed. Nine patients were excluded for technical reasons and 3 for protocol violations. Twenty-four videos were read as normal and 14 as abnormal from both capsules. Disagreement occurred in 13. No adverse events were reported for either capsule. Overall agreement was 38 of 51 (74.5%) with a kappa of 0.48, P = .008. LIMITATIONS Although ingestion order was randomized, the videos could not be read blind owing to a different shape of the image margin. CONCLUSIONS (1) Both devices were safe and had a comparable diagnostic yield within the range previously reported. (2) There was a subjective difference in image quality favoring the EC. (3) This study design provided unique information about capsule movement in the small intestine and the lack of electromechanical interference between 2 different capsules.","author":[{"dropping-particle":"","family":"Cave","given":"David R","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fleischer","given":"David E","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leighton","given":"Jonathan A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Faigel","given":"Douglas O","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Heigh","given":"Russell I","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sharma","given":"Virender K","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gostout","given":"Christopher J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rajan","given":"Elizabeth","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mergener","given":"Klaus","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Foley","given":"Anne","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lee","given":"Michael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bhattacharya","given":"Kanishka","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastrointestinal endoscopy","id":"ITEM-6","issue":"3","issued":{"date-parts":[["2008","9"]]},"page":"487-94","title":"A multicenter randomized comparison of the Endocapsule and the Pillcam SB.","type":"article-journal","volume":"68"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>38–43</sup>","plainTextFormattedCitation":"38–43","previouslyFormattedCitation":"<sup>38–43</sup>"},"properties":{"noteIndex":0},"schema":""}38–43. The reliance of CE solely on WLI technology currently restricts it to the detection of mucosal manifestations of disease and prevents the evaluation of submucosal and transmural pathologyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1007/978-4-431-78889-8","ISBN":"978-4-431-78888-1","editor":[{"dropping-particle":"","family":"Niwa","given":"Hirohumi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tajiri","given":"Hisao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nakajima","given":"Masatsugu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yasuda","given":"Kenjiro","non-dropping-particle":"","parse-names":false,"suffix":""}],"id":"ITEM-1","issued":{"date-parts":[["2008"]]},"publisher":"Springer Japan","publisher-place":"Tokyo","title":"New Challenges in Gastrointestinal Endoscopy","type":"book"},"uris":["",""]}],"mendeley":{"formattedCitation":"<sup>44</sup>","plainTextFormattedCitation":"44","previouslyFormattedCitation":"<sup>44</sup>"},"properties":{"noteIndex":0},"schema":""}44. Furthermore, reliance on WLI alone opens up interpretation challenges regarding visually obscured or occult lesions, variability in appearance, non-homogeneous distribution and occurrence in microfociADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1038/nature06005","ISBN":"00280836","ISSN":"0028-0836","PMID":"25904573","abstract":"Recently, substantial advances in the understanding of the molecular pathogenesis of inflammatory bowel disease (IBD) have been made owing to three related lines of investigation. First, IBD has been found to be the most tractable of complex disorders for discovering susceptibility genes, and these have shown the importance of epithelial barrier function, and innate and adaptive immunity in disease pathogenesis. Second, efforts directed towards the identification of environmental factors implicate commensal bacteria (or their products), rather than conventional pathogens, as drivers of dysregulated immunity and IBD. Third, murine models, which exhibit many of the features of ulcerative colitis and seem to be bacteria-driven, have helped unravel the pathogenesis/mucosal immunopathology of IBD. [ABSTRACT FROM AUTHOR] Copyright of Nature is the property of Nature Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)","author":[{"dropping-particle":"","family":"Xavier","given":"R J Podolsky D K","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Nature","id":"ITEM-1","issue":"7152","issued":{"date-parts":[["2007"]]},"page":"427-434","title":"Unravelling the pathogenesis of inflammatory bowel disease","type":"article-journal","volume":"448"},"uris":["",""]},{"id":"ITEM-2","itemData":{"DOI":"10.1016/pbiomed.2015.04.019","ISSN":"18790534","abstract":"Although many groups have attempted to develop an automated computerized method to detect pathology of the small intestinal mucosa caused by celiac disease, the efforts have thus far failed. This is due in part to the occult presence of the disease. When pathological evidence of celiac disease exists in the small bowel it is visually often patchy and subtle. Due to presence of extraneous substances such as air bubbles and opaque fluids, the use of computerized automation methods have only been partially successful in detecting the hallmarks of the disease in the small intestine-villous atrophy, fissuring, and a mottled appearance. By using a variety of computerized techniques and assigning a weight or vote to each technique, it is possible to improve the detection of abnormal regions which are indicative of celiac disease, and of treatment progress in diagnosed patients. Herein a paradigm is suggested for improving the efficacy of automated methods for measuring celiac disease manifestation in the small intestinal mucosa. The suggestions are applicable to both standard and videocapsule endoscopic imaging, since both methods could potentially benefit from computerized quantitation to improve celiac disease diagnosis.","author":[{"dropping-particle":"","family":"Ciaccio","given":"Edward J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bhagat","given":"Govind","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lewis","given":"Suzanne K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Green","given":"Peter H.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Computers in Biology and Medicine","id":"ITEM-2","issued":{"date-parts":[["2015","10"]]},"page":"364-368","publisher":"Elsevier","title":"Suggestions for automatic quantitation of endoscopic image analysis to improve detection of small intestinal pathology in celiac disease patients","type":"article-journal","volume":"65"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>45,46</sup>","plainTextFormattedCitation":"45,46","previouslyFormattedCitation":"<sup>45,46</sup>"},"properties":{"noteIndex":0},"schema":""}45,46. Additionally, the specificity of diagnosis based on visual changes is not reliable owing to similarities in the mucosal appearance of different small bowel diseases such as celiaccoeliac disease, microscopic colitis and inflammatory bowel diseaseIBDADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1136/jcp.2005.035345","ISBN":"0021-9746","ISSN":"0021-9746","PMID":"17021129","abstract":"Coeliac disease is the manifestation of an immune hypersensitivity reaction towards gluten and related proteins, in genetically predisposed people. Although the precise pathogenesis of this condition remains to be fully elucidated, it is probably multifactorial in origin. The diagnosis of coeliac disease has traditionally depended on intestinal biopsies alone; nowadays, the diagnosis has been expanded to include an array of serological markers. This review is intended to offer pathologists an update of the relevant history and immunopathology pertaining to coeliac disease and also to offer recommendations on the ongoing responsibilities of the pathologist in the diagnosis and reporting of coeliac disease.","author":[{"dropping-particle":"","family":"Dickson","given":"B C","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Streutker","given":"C J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chetty","given":"R","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of clinical pathology","id":"ITEM-1","issue":"10","issued":{"date-parts":[["2006"]]},"page":"1008-16","title":"Coeliac disease: an update for pathologists.","type":"article-journal","volume":"59"},"uris":["",""]}],"mendeley":{"formattedCitation":"<sup>47</sup>","plainTextFormattedCitation":"47","previouslyFormattedCitation":"<sup>47</sup>"},"properties":{"noteIndex":0},"schema":""}47. Finally, sensitivity declines when encountering low grade diseases that have not fully manifested themselves to the human eyeADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.3748/wjg.v18.i31.4095","ISSN":"2219-2840","PMID":"22919241","abstract":"Celiac disease (CD) is an autoimmune inflammatory disease of the small intestine as a result of reaction to wheat protein, gluten. Exclusion of dietary gluten is the mainstay of the treatment that necessitates a precise diagnosis of the disease. Serological screening may aid in identifying patients with suspected CD, which should be confirmed by intestinal biopsy. It has been shown that duodenal biopsies are good for detection of the disease in most patients. However, there is a group of patients with positive serology and inconclusive pathology. As a result of the widespread use of serology, many patients with equivocal findings grow quickly. Unfortunately current endoscopic methods can only diagnose villous atrophy, which can be present in the later grades of disease (i.e., Marsh III). To diagnose CD correctly, going deeper in the intestine may be necessary. Enteroscopy can reveal changes in CD in the intestinal mucosa in 10%-17% of cases that have negative histology at initial workup. Invasiveness of the method limits its use. Capsule endoscopy may be a good substitute for enteroscopy. However, both techniques should be reserved for patients with suspected diagnosis of complications. This paper reviews the current literature in terms of the value of enteroscopy for diagnosis of CD.","author":[{"dropping-particle":"","family":"Kav","given":"Taylan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sivri","given":"Bulent","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"World journal of gastroenterology : WJG","id":"ITEM-1","issue":"31","issued":{"date-parts":[["2012","8"]]},"page":"4095-101","title":"Is enteroscopy necessary for diagnosis of celiac disease?","type":"article-journal","volume":"18"},"uris":["",""]}],"mendeley":{"formattedCitation":"<sup>48</sup>","plainTextFormattedCitation":"48","previouslyFormattedCitation":"<sup>48</sup>"},"properties":{"noteIndex":0},"schema":""}48. [H1]Taxonomy of Diagnostic Capsules In the past few years, research on CE as a platform to improve diagnosis of gastrointestinal disease and to understand the underlying pathophysiology has expanded. Two research trends have been observed with regards to diagnosis. The first is the use of alternative imaging technologies, such as ultrasonography, fluorescence imaging and optical coherence tomography (OCT) and the second is the integration of non-image-based sensors for the measurement of physiological parameters such as pH, pressure or temperature. As seen in REF _Ref536004973 \h \* MERGEFORMAT Table 3, capsules with these capabilities are still in early development with technical challenges to be overcome and further clinical testing required. [H2]Alternative Imaging Visualizing the gastrointestinal tract using imaging alternative to WLI has the potential to enable observation of previously unseen features, and to improve diagnostic sensitivity, specificity and accuracy. Attempts to overcome the recognized limitations of WLI in conventional endoscopy have spurred development of alternative imaging technologies such as narrow-band imaging (NBI) and chromoendoscopyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1007/s10620-017-4772-y","ISSN":"0163-2116","author":[{"dropping-particle":"","family":"Har-Noy","given":"Ofir","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Katz","given":"Lior","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Avni","given":"Tomer","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Battat","given":"Robert","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bessissow","given":"Talat","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yung","given":"Diana E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Engel","given":"Tal","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Koulaouzidis","given":"Anastasios","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Eliakim","given":"Rami","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ben-Horin","given":"Shomron","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kopylov","given":"Uri","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Digestive Diseases and Sciences","id":"ITEM-1","issue":"11","issued":{"date-parts":[["2017","11","30"]]},"page":"2982-2990","title":"Chromoendoscopy, Narrow-Band Imaging or White Light Endoscopy for Neoplasia Detection in Inflammatory Bowel Diseases","type":"article-journal","volume":"62"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1038/nrgastro.2017.46","ISSN":"1759-5045","author":[{"dropping-particle":"","family":"Hoffman","given":"Arthur","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Manner","given":"Henrik","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rey","given":"Johannes W.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kiesslich","given":"Ralf","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Nature Reviews Gastroenterology & Hepatology","id":"ITEM-2","issue":"7","issued":{"date-parts":[["2017","6","14"]]},"page":"421-434","title":"A guide to multimodal endoscopy imaging for gastrointestinal malignancy — an early indicator","type":"article-journal","volume":"14"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>49,50</sup>","plainTextFormattedCitation":"49,50","previouslyFormattedCitation":"<sup>49,50</sup>"},"properties":{"noteIndex":0},"schema":""}49,50. Both methods increase tissue contrast to improve visualization but by different means. NBI incorporates optical filters so that only blue (415 nm wavelength) and green (540 nm wavelength) light is emitted, thereby enhancing the appearance of superficial mucosal capillaries and mucosal surface patterns and increasing hemoglobin absorption to make blood vessels appear darker. In chromoendoscopy, various dye solutions are sprayed on to the gastrointestinal mucosa to improve the detection of subtle mucosal dysplastic changes associated with chronic inflammatory bowel diseasesIBDs, such as ulcerative colitis. Disadvantages of the use of exogenous markers include potentially unequal distribution, pooling which can obscure lesions, and lengthening of the duration of the procedureADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"ISBN":"9780323311632","author":[{"dropping-particle":"","family":"Kaltenbach","given":"Tonya","non-dropping-particle":"","parse-names":false,"suffix":""}],"editor":[{"dropping-particle":"","family":"1","given":"","non-dropping-particle":"","parse-names":false,"suffix":""}],"id":"ITEM-1","issued":{"date-parts":[["2014"]]},"publisher":"Elsevier","title":"Nonpolypoid Colorectal Neoplasms in Inflammatory Bowel Disease","type":"book"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>51</sup>","plainTextFormattedCitation":"51","previouslyFormattedCitation":"<sup>51</sup>"},"properties":{"noteIndex":0},"schema":""}51. These imaging modalities have also been integrated into CEADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.sna.2014.10.033","ISSN":"09244247","author":[{"dropping-particle":"","family":"Khan","given":"Tareq H.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shrestha","given":"Ravi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wahid","given":"Khan A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Babyn","given":"Paul","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Sensors and Actuators A: Physical","id":"ITEM-1","issued":{"date-parts":[["2015","1"]]},"page":"77-87","title":"Design of a smart-device and FPGA based wireless capsule endoscopic system","type":"article-journal","volume":"221"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1016/j.image.2013.12.001","ISSN":"09235965","author":[{"dropping-particle":"","family":"Khan","given":"Tareq Hasan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wahid","given":"Khan A.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Signal Processing: Image Communication","id":"ITEM-2","issue":"3","issued":{"date-parts":[["2014","3"]]},"page":"345-360","title":"White and narrow band image compressor based on a new color space for capsule endoscopy","type":"article-journal","volume":"29"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1016/j.dld.2011.07.018","ISSN":"15908658","PMID":"21893436","abstract":"Introduction: Virtual chromoendoscopy is used to enhance surface patterns and colour differences. One type of virtual chromoendoscopy is the Fuji Intelligent Colour Enhancement (FICE). Although widely applied in conventional endoscopy, data on FICE application in capsule endoscopy are limited. Furthermore, the validity of Blue filter (feature of RAPID ?? software) has not been examined. Aim/s: We aimed to qualitatively evaluate the use of FICE and Blue filter enhancement, in images of lesions obtained during small bowel capsule endoscopy, comparing them with similar, conventional (white light) images. Methods: A total of 167 images (6 different lesion categories) obtained from 200 capsule endoscopy examinations. Two gastroenterologists examined the images with white light, FICE and Blue filter in regards to the visibility of blood vessels, the contrast of the mucosal surface, and the demarcation of lesion borders. The agreed scores were: improved, similar, worse. Inter-observer agreement was calculated. Results: For all lesion categories, Blue filter provided image improvement (compared to white light) in 83%, (inter-observer agreement: 0.786). With FICE 1, improvement was observed in 34%, worse image in 55.9%, (inter-observer agreement: 0.646). With FICE 2, improvement was observed in 8.6%, worse in 77.5%, (inter-observer agreement: 0.617). With FICE 3, improvement was seen in 7.7%, worse in 79.9% (inter-observer agreement: 0.669). Conclusion: Comparing with FICE, Blue filter offers better image enhancement in capsule endoscopy. ?? 2011 Editrice Gastroenterologica Italiana S.r.l.","author":[{"dropping-particle":"","family":"Krystallis","given":"Christoforos","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Koulaouzidis","given":"Anastasios","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Douglas","given":"Sarah","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Plevris","given":"John N.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Digestive and Liver Disease","id":"ITEM-3","issue":"12","issued":{"date-parts":[["2011"]]},"page":"953-957","publisher":"Editrice Gastroenterologica Italiana","title":"Chromoendoscopy in small bowel capsule endoscopy: Blue mode or Fuji Intelligent Colour Enhancement?","type":"article-journal","volume":"43"},"uris":[""]},{"id":"ITEM-4","itemData":{"DOI":"10.1016/j.gie.2010.10.016","ISSN":"00165107","author":[{"dropping-particle":"","family":"Imagawa","given":"Hiroki","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Oka","given":"Shiro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tanaka","given":"Shinji","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Noda","given":"Ikue","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Higashiyama","given":"Makoto","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sanomura","given":"Youji","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shishido","given":"Takayoshi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yoshida","given":"Shigeto","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chayama","given":"Kazuaki","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastrointestinal Endoscopy","id":"ITEM-4","issue":"2","issued":{"date-parts":[["2011","2"]]},"page":"299-306","title":"Improved visibility of lesions of the small intestine via capsule endoscopy with computed virtual chromoendoscopy","type":"article-journal","volume":"73"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>52–55</sup>","plainTextFormattedCitation":"52–55","previouslyFormattedCitation":"<sup>52–55</sup>"},"properties":{"noteIndex":0},"schema":""}52–55 but studies have cast doubt on their efficacy compared with standard WLI capsulesADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.gie.2013.01.029","ISBN":"1097-6779 (Electronic)\\n0016-5107 (Linking)","ISSN":"00165107","PMID":"23433595","abstract":"Background: New endoscopic imaging techniques, such as autofluorescence imaging (AFI) and narrow-band imaging (NBI), have been developed to improve the detection of neoplastic lesions in Barrett's esophagus (BE). Objective: To evaluate the clinical utility of AFI and magnification NBI to detect high-grade dysplasia (HGD) and early esophageal adenocarcinoma (EAC) and the interobserver agreement. Design: Prospective tandem study of eligible patients. Setting: Single, academic tertiary care center. Patients: Forty-two patients with a history of confirmed BE were prospectively enrolled. Interventions: The BE segment was examined under high-definition white-light endoscopy, and the presence of visible lesions was recorded. Subsequently, AFI and magnification NBI were performed in tandem on areas of the BE segment away from visible lesions; images obtained by these 2 systems were graded according to the color of reflected light and surface patterns, respectively. Biopsy specimens were obtained at the end of the procedure. Main Outcome Measurements: The sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of the AFI and NBI patterns for the detection of HGD/EAC and interobserver agreement. Results: Of the 42 patients enrolled, 14 (33%) had HGD/EAC. On patient-based analysis, AFI alone had a sensitivity, specificity, and NPV of 50%, 61%, and 71%, respectively, and the overall accuracy for the detection of HGD/EAC patients was 57%. By using magnification NBI in tandem fashion, the sensitivity and NPV improved to 71% and 76%, respectively, with a decrease in specificity to 46% and in overall accuracy to 55%. The 2 techniques had moderate interobserver agreement for both the patterns and prediction of histology. Limitations: Uncontrolled study performed at an academic center by expert endoscopists in a high-risk population. Conclusions: By using a multimodality endoscope, both AFI and magnification NBI had limited clinical accuracy and moderate overall interobserver agreement. AFI does not appear to be useful as a broad-based technique for the detection of neoplasia in patients with BE. ? 2013 American Society for Gastrointestinal Endoscopy.","author":[{"dropping-particle":"","family":"Giacchino","given":"Maria","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bansal","given":"Ajay","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kim","given":"Raymond E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Singh","given":"Vikas","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hall","given":"Sandy B.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Singh","given":"Mandeep","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rastogi","given":"Amit","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Moloney","given":"Brian","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wani","given":"Sachin B.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gaddam","given":"Srinivas","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mathur","given":"Sharad C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wallace","given":"Michael B.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kanakadandi","given":"Vijay","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Balasubramanian","given":"Gokulakrishnan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gupta","given":"Neil","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sharma","given":"Prateek","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastrointestinal Endoscopy","id":"ITEM-1","issue":"5","issued":{"date-parts":[["2013"]]},"page":"711-718","title":"Clinical utility and interobserver agreement of autofluorescence imaging and magnification narrow-band imaging for the evaluation of Barrett's esophagus: A prospective tandem study","type":"article-journal","volume":"77"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1016/j.gie.2010.09.023","ISBN":"1097-6779 (Electronic)\\r0016-5107 (Linking)","ISSN":"00165107","PMID":"21184868","abstract":"Background: Three different classification systems for the evaluation of Barrett's esophagus (BE) using magnification endoscopy (ME) and narrow-band imaging (NBI) have been proposed. Until now, no comparative and external evaluation of these systems in a clinical-like situation has been performed. Objective To compare and validate these 3 classification systems. Design Prospective validation study. Setting Tertiary-care referral center. Nine endoscopists with different levels of expertise from Europe and Japan participated as assessors. Patients Thirty-two patients with long-segment BE. Interventions From a group of 209 standardized prospective recordings collected on BE by using ME combined with NBI, 84 high-quality videos were randomly selected for evaluation. Histologically, 28 were classified as gastric type mucosa, 29 as specialized intestinal metaplasia (SIM), and 27 as SIM with dysplasia/cancer. Assessors were blinded to underlying histology and scored each video according to the respective classification system. Before evaluation, an educational set concerning each classification system was carefully studied. At each assessment, the same 84 videos were displayed, but in different and random order. Main Outcome Measurements Accuracy for detection of nondysplastic and dysplastic SIM. Interobserver agreement related to each classification. Results The median time for video evaluation was 25 seconds (interquartile range 20-39 seconds) and was longer with the Amsterdam classification (P < .001). In 65% to 69% of the videos, assessors described certainty about the histology prediction. The global accuracy was 46% and 47% using the Nottingham and Kansas classifications, respectively, and 51% with the Amsterdam classification. The accuracy for nondysplastic SIM identification ranged between 57% (Kansas and Nottingham) and 63% (Amsterdam). Accuracy for dysplastic tissue was 75%, irrespective of the classification system and assessor expertise level. Interobserver agreement ranged from fair (Nottingham, κ = 0.34) to moderate (Amsterdam and Kansas, κ = 0.47 and 0.44, respectively). Limitation No per-patient analysis. Conclusions All of the available classification systems could be used in a clinical-like environment, but with inadequate interobserver agreement. All classification systems based on combined ME and NBI, revealed substantial limitations in predicting nondysplastic and dysplastic BE when assessed externally. This technique cannot, as yet, repla…","author":[{"dropping-particle":"","family":"Silva","given":"Francisco Baldaque","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dinis-Ribeiro","given":"Mrio","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Vieth","given":"Michael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rabenstein","given":"Thomas","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Goda","given":"Kenichi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kiesslich","given":"Ralf","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Haringsma","given":"Jelle","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Edebo","given":"Anders","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Toth","given":"Ervin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Soares","given":"Jos","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Areia","given":"Miguel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lundell","given":"Lars","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Marschall","given":"Hanns Ulrich","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastrointestinal Endoscopy","id":"ITEM-2","issue":"1","issued":{"date-parts":[["2011"]]},"page":"7-14","title":"Endoscopic assessment and grading of Barrett's esophagus using magnification endoscopy and narrow-band imaging: Accuracy and interobserver agreement of different classification systems (with videos)","type":"article-journal","volume":"73"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1038/ajg.2011.436","ISBN":"0016-5107","ISSN":"0002-9270","PMID":"22186978","abstract":"OBJECTIVES Colonoscopy has an appreciable miss rate for adenomas and colorectal cancer. The goal of advanced endoscopic imaging is to improve lesion detection. Compared with standard definition, high-definition (HD) colonoscopes have the advantage of increased field of visualization and higher resolution; narrow band imaging (NBI) utilizes narrow band filters for enhanced visualization of surface architecture and capillary pattern. The objective of this study was to compare the yield and miss rates of HD-NBI and HD-WLE (white light endoscopy) for the detection of colon polyps using meta-analysis. METHODS A recursive literature search of randomized controlled trials (RCTs) comparing the yield of HD-NBI and HD-WLE for detection of colon polyps in patients undergoing screening/surveillance colonoscopy. Authors were contacted for missing data. In RCT with tandem colonoscopy (RCT-t), findings from the first-pass examinations were used in the yield analysis and from the tandem pass for the miss rate analysis. Data on the yield of polyps were extracted, pooled, and analyzed using RevMan 4.2.9 software. Odds ratio (OR) and 95% confidence intervals (CIs) for the pooled data for the yield and miss rates of NBI and WLE were calculated. A fixed effect model (FEM) was used for analyses without, and a random effect model (REM) for analyses with heterogeneity. RESULTS The yield analysis revealed no significant difference between HD-NBI and HD-WLE for the detection of adenomas (six studies; n=2,284; OR: 1.01; CI: 0.74-1.37; REM); patients with polyps (six studies; n=2,275; OR: 1.15; CI: 0.8-1.64; REM); patients with adenomas (four studies; n=2,177; OR: 1.0; CI: 0.83-1.20; FEM); detection of adenomas <10 mm (five studies; n=1,618; OR: 1.32; CI: 0.92-1.88; FEM); flat adenomas (five studies; n=1,675; OR: 1.26; CI: 0.62-2.57; REM); and flat adenomas per patient (five studies; n=2,200; OR: 1.63; CI: 0.71-3.74; REM). The miss rate analysis revealed no difference in polyp miss rate (three studies; n=524; OR: 1.17; CI: 0.8-1.71; FEM) or adenoma miss rate (three studies; n=524; OR: 0.65; CI: 0.4-1.06; FEM) between the two techniques. CONCLUSIONS Compared with HD-WLE, HD-NBI does not increase the yield of colon polyps, adenomas, or flat adenomas, nor does it decrease the miss rate of colon polyps or adenomas in patients undergoing screening/surveillance colonoscopy.","author":[{"dropping-particle":"","family":"Pasha","given":"Shabana F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leighton","given":"Jonathan A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Das","given":"Ananya","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Harrison","given":"M. Edwyn","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gurudu","given":"Suryakanth R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ramirez","given":"Francisco C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fleischer","given":"David E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sharma","given":"Virender K.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"The American Journal of Gastroenterology","id":"ITEM-3","issue":"3","issued":{"date-parts":[["2012","3","20"]]},"page":"363-370","title":"Comparison of the Yield and Miss Rate of Narrow Band Imaging and White Light Endoscopy in Patients Undergoing Screening or Surveillance Colonoscopy: A Meta-Analysis","type":"article-journal","volume":"107"},"uris":[""]},{"id":"ITEM-4","itemData":{"DOI":"10.4253/wjge.v9.i6.273","ISSN":"1948-5190","abstract":"AIM To compare high definition white light endoscopy and bright narrow band imaging for colon polyps’ detection rates. METHODS Patients were randomised to high definition white light endoscopy (HD-WLE) or the bright narrow band imaging (bNBI) during withdrawal of the colonoscope. Polyps identified in either mode were characterised using bNBI with dual focus (bNBI-DF) according to the Sano’s classification. The primary outcome was to compare adenoma detection rates (ADRs) between the two arms. The secondary outcome was to assess the negative predictive value (NPV) in differentiating adenomas from hyperplastic polyps for diminutive rectosigmoid lesions. RESULTS A total of 1006 patients were randomised to HD-WLE (n = 511) or bNBI (n = 495). The mean of adenoma per patient was 1.62 and 1.84, respectively. The ADRs in bNBI and HD-WLE group were 37.4% and 39.3%, respectively. When adjusted for withdrawal time (OR = 1.19, 95%CI: 1.15-1.24, P < 0.001), the use of bNBI was associated with a reduced ADR (OR = 0.69, 95%CI: 0.52-0.92). Nine hundred and thirty three polyps (86%) in both arms were predicted with high confidence. The sensitivity (Sn), specificity (Sp), positive predictive value and NPV in differentiating adenomatous from non-adenomatous polyps of all sizes were 95.9%, 87.2%, 94.0% and 91.1% respectively. The NPV in differentiating an adenoma from hyperplastic polyp using bNBI-DF for diminutive rectal polyps was 91.0%. CONCLUSION ADRs did not differ between bNBI and HD-WLE, however HD-WLE had higher ADR after adjustment of withdrawal time. bNBI surpassed the PIVI threshold for diminutive polyps.","author":[{"dropping-particle":"","family":"Singh","given":"Rajvinder","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cheong","given":"Kuan Loong","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pu","given":"Leonardo Zorron Cheng Tao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mangira","given":"Dileep","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Koay","given":"Doreen Siew Ching","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kee","given":"Carmen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ng","given":"Siew Chien","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rerknimitr","given":"Rungsun","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Aniwan","given":"Satimai","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ang","given":"Tiing-Leong","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Goh","given":"Khean-Lee","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ho","given":"Shiaw Hooi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lau","given":"James Yun-Wong","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"World Journal of Gastrointestinal Endoscopy","id":"ITEM-4","issue":"6","issued":{"date-parts":[["2017"]]},"page":"273","title":"Multicenter randomised controlled trial comparing the high definition white light endoscopy and the bright narrow band imaging for colon polyps","type":"article-journal","volume":"9"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>56–59</sup>","plainTextFormattedCitation":"56–59","previouslyFormattedCitation":"<sup>56–59</sup>"},"properties":{"noteIndex":0},"schema":""}56–59. Other alternative imaging technologies such as ?US, fluorescent imaging and OCT address some of the limitations associated with WLI technology. Examples of some of these imaging modalities are shown in REF _Ref536629639 \h Fig. 1.[H3] Ultrasonographic imaging Following the acceptability of endoscopic ultrasonography (EUS) in routine clinical use, the inclusion of ultrasonography into a capsule was a desirable step to improve CE diagnostic capabilities beyond optical imaging. The development of ultrasonographic capsule endoscopy (USCE) is currently in its infancy and was recently being developed by a number of teams, including the Khuri-YakubADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/ULTSYM.2016.7728851","ISBN":"978-1-4673-9897-8","abstract":"We are developing a capsule ultrasound (CUS) device - a pill with the capability to scan the gastrointestinal (GI) tract through ultrasound. In this paper, we discuss the design and fabrication of the main components of the CUS device including the CMUT array, front-end electronics, and the wireless transmitter. We demonstrate a successfully fabricated 128-element CMUT array with polydimethylsiloxane (PDMS)-filled trenches and show their input impedance in air. The front-end electronics, measuring 6 mm by 6 mm and the high-data rate wireless transmitter, measuring 1 mm by 1.76 mm, have been fabricated. Our preliminary power analysis indicates that our total power consumption is less than 20 mW for the CUS device. Our future work involves integrating these core components for imaging experiments.","author":[{"dropping-particle":"","family":"Memon","given":"Farah","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Touma","given":"Gerard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wang","given":"Junyi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Baltsavias","given":"Spyridon","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Moini","given":"Azadeh","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chang","given":"Chienliu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rasmussen","given":"Morten Fischer","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nikoozadeh","given":"Amin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Choe","given":"Jung Woo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Olcott","given":"Eric","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jeffrey","given":"R. 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However, it suffers from a number of well recognized deficiencies. Amongst these is the limited capability of white light imaging, which is restricted to analysis of the mucosal surface. Current capsule endoscopes are dependent on visual manifestation of disease and limited in regards to transmural imaging and detection of deeper pathology. Ultrasound capsule endoscopy (USCE) has the potential to overcome surface only imaging and provide transmural scans of the GI tract. The integration of high frequency microultrasound (?US) into capsule endoscopy would allow high resolution transmural images and provide a means of both qualitative and quantitative assessment of the bowel wall. Quantitative ultrasound (QUS) can provide data in an objective and measurable manner, potentially reducing lengthy interpretation times by incorporation into an automated diagnostic process. The research described here is focused on the development of USCE and other complementary diagnostic and therapeutic modalities. Presently investigations have entered a preclinical phase with laboratory investigations running concurrently.","author":[{"dropping-particle":"","family":"Cox","given":"Benjamin F. B.F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stewart","given":"Fraser","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lay","given":"Holly","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cummins","given":"Gerard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Newton","given":"I.P. Ian P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Desmulliez","given":"Marc P. Y. M.P. 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Previous attempts have included the Endoscope Capsule using Ultrasound Technology (TROY)ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"author":[{"dropping-particle":"","family":"Correia","given":"Jo?o","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"INSTITUTO AGILUS DE INOVA?AO EM TECNOLOGIAS DE INFORMA?AO S.A MATOSINHOS","id":"ITEM-1","issued":{"date-parts":[["2009"]]},"title":"TROY: Endoscope Capsule Using Ultrasound Technology, Final Report","type":"report"},"uris":["",""]}],"mendeley":{"formattedCitation":"<sup>63</sup>","plainTextFormattedCitation":"63","previouslyFormattedCitation":"<sup>63</sup>"},"properties":{"noteIndex":0},"schema":""}63 project, which that was unable to miniaturize the system to fit within the dimensions of a swallowable capsule before the end of the project and work by Lee et al.ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/ULTSYM.2014.0181","ISBN":"978-1-4799-7049-0","abstract":"Wireless capsule endoscopy (WCE) has revolutionized the capacity for evaluation of the gastrointestinal (GI) tract. Although WCE provides high quality images of the GI tract, evaluation is limited to the mucosal surface. This work investigates feasibility and design considerations for wireless capsule endoscopic ultrasound (WCEU) that combines the benefits of WCE and ultrasound imaging. This work has two goals: (1) evaluate transducer designs appropriate for WCEU and (2) investigate whether peristalsis can produce sufficient contact to ensure acoustic coupling. Between mechanical scanning (MS) and side-looking array (SLA) designs, MS performs better for both imaging performance and system complexity. In vivo imaging in pigs demonstrates promising results, although the effect of peristalsis and resulting coverage needs further investigation and quantification.","author":[{"dropping-particle":"","family":"Lee","given":"John H.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Traverso","given":"Giovanni","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schoellhammer","given":"Carl M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Blankschtein","given":"Daniel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Langer","given":"Robert","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Thomenius","given":"Kai E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Boning","given":"Duane S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Anthony","given":"Brian W.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"2014 IEEE International Ultrasonics Symposium","id":"ITEM-1","issued":{"date-parts":[["2014","9"]]},"page":"734-737","publisher":"IEEE","title":"Towards wireless capsule endoscopic ultrasound (WCEU)","title-short":"Ultrasonics Symposium (IUS), 2014 IEEE Internation","type":"paper-conference"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>64</sup>","plainTextFormattedCitation":"64","previouslyFormattedCitation":"<sup>64</sup>"},"properties":{"noteIndex":0},"schema":""}64, which was not able to identify a suitable means for achieving long-term rotation of the ultrasound transducer, al though theyit produced a capsule with the required dimensions that was successfully tested in vivo, was not able to identify a suitable means for achieving long-term rotation of the ultrasound transducer. The common aim of these projects was to develop a capsule capable of transmural gastrointestinal imaging to detect submucosal (intramural) pathology.At the heart of USCE is the development and integration of a suitable ultrasound transducer. Both Khuri-Yakub et al. and Cochran et al. have explored the possibility of fabricating miniaturized multi-element ring arrays capable of providing a 360o image of the bowel wallADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1088/0960-1317/24/10/107002","ISBN":"0324141122","ISSN":"13616439","PMID":"24655651","abstract":"? 2014 IOP Publishing Ltd. Singulation of MEMS is a critical step in the transition from wafer-level to die-level devices. As is the case for capacitive micromachined ultrasound transducer (CMUT) ring arrays, an ideal singulation must protect the fragile membranes from the processing environment while maintaining a ring array geometry. The singulation process presented in this paper involves bonding a trench-patterned CMUT wafer onto a support wafer, deep reactive ion etching (DRIE) of the trenches, separating the CMUT wafer from the support wafer and de-tethering the CMUT device from the CMUT wafer. The CMUT arrays fabricated and singulated in this process were ring-shaped arrays, with inner and outer diameters of 5 mm and 10 mm, respectively. The fabricated CMUT ring arrays demonstrate the ability of this method to successfully and safely singulate the ring arrays and is applicable to any arbitrary 2D shaped MEMS device with uspended microstructures, taking advantage of the inherent planar attributes of DRIE.","author":[{"dropping-particle":"","family":"Chang","given":"Chienliu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Moini","given":"Azadeh","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nikoozadeh","given":"Amin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sarioglu","given":"Ali Fatih","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Apte","given":"Nikhil","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zhuang","given":"Xuefeng","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Khuri-Yakub","given":"Butrus T","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Micromechanics and Microengineering","id":"ITEM-1","issue":"10","issued":{"date-parts":[["2014","10"]]},"page":"107002","title":"Singulation for imaging ring arrays of capacitive micromachined ultrasonic transducers","type":"article-journal","volume":"24"},"uris":["",""]},{"id":"ITEM-2","itemData":{"DOI":"10.1109/TUFFC.2018.2794220","ISSN":"08853010","abstract":"Video capsule endoscopy (VCE) has significantly advanced visualization of the gastrointestinal tract (GI tract) since its introduction in the last 20 years. Work is now under way to combine VCE with microultrasound imaging. However, small maximum capsule dimensions, coupled with the electronics required to integrate ultrasound imaging capabilities, pose significant design challenges. This paper describes a simulation process for testing transducer geometries and imaging methodologies to achieve satisfactory imaging performance within the physical limitations of the capsule size and outlines many of the trade-offs needed in the design of this new class of ultrasound capsule endoscopy (USCE) device. A hybrid MATLAB model is described, incorporating KLM circuit elements and digitizing and beamforming elements to render a grey-scale B-mode. This model is combined with a model of acoustic propagation to generate images of point scatterers. The models are used to demonstrate the performance of a USCE transducer configuration comprising a single, unfocused transmit ring of radius 5 mm separated into eight segments for electrical impedance control and a 512-element receive linear array, also formed into a ring. The MATLAB model includes an ultrasonic pulser circuit connected to a piezocrystal composite transmit transducer with a center frequency of 25 MHz. B-scan images are simulated for wire target phantoms, multilayered phantoms, and a gut wall model. To demonstrate the USCE system’s ability to image tissue, a digital phantom was created from single-element ultrasonic transducer scans of porcine small bowel ex vivo obtained at a frequency of 45 MHz.","author":[{"dropping-particle":"","family":"Lay","given":"Holly S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cox","given":"Benjamin F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Seetohul","given":"Vipin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Demore","given":"Christine E.M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cochran","given":"Sandy","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control","id":"ITEM-2","issue":"4","issued":{"date-parts":[["2018"]]},"page":"589-599","title":"Design and Simulation of a Ring-Shaped Linear Array for Microultrasound Capsule Endoscopy","type":"article-journal","volume":"65"},"uris":["",""]}],"mendeley":{"formattedCitation":"<sup>65,66</sup>","plainTextFormattedCitation":"65,66","previouslyFormattedCitation":"<sup>65,66</sup>"},"properties":{"noteIndex":0},"schema":""}65,66. Cochran has also focused on single-element transducers, as have Qiu and LeeADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/TMI.2017.2699973","ISBN":"2014061015185","ISSN":"0278-0062","author":[{"dropping-particle":"","family":"Wang","given":"Xingying","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Seetohul","given":"Vipin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chen","given":"Ruimin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zhang","given":"Zhiqiang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Qian","given":"Ming","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shi","given":"Zhehao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yang","given":"Ge","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mu","given":"Peitian","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wang","given":"Congzhi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Huang","given":"Zhihong","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zhou","given":"Qifa","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zheng","given":"Hairong","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cochran","given":"Sandy","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Qiu","given":"Weibao","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Transactions on Medical Imaging","id":"ITEM-1","issue":"9","issued":{"date-parts":[["2017","9"]]},"page":"1922-1929","title":"Development of a Mechanical Scanning Device With High-Frequency Ultrasound Transducer for Ultrasonic Capsule Endoscopy","type":"article-journal","volume":"36"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1109/TBME.2018.2852715","ISSN":"0018-9294","author":[{"dropping-particle":"","family":"Lay","given":"Holly","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cummins","given":"Gerard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cox","given":"Benjamin F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Qiu","given":"Yongqiang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Turcanu","given":"Mihnea Vlad","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"McPhillips","given":"Rachael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Connor","given":"Ciaran","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gregson","given":"Rachael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Clutton","given":"Eddie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Desmulliez","given":"Marc P.Y.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cochran","given":"Sandy","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Transactions on Biomedical Engineering","id":"ITEM-2","issue":"3","issued":{"date-parts":[["2018"]]},"page":"632 - 639","title":"In-Vivo Evaluation of Microultrasound and Thermometric Capsule Endoscopes","type":"article-journal","volume":"66"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1109/ULTSYM.2014.0181","ISBN":"978-1-4799-7049-0","abstract":"Wireless capsule endoscopy (WCE) has revolutionized the capacity for evaluation of the gastrointestinal (GI) tract. Although WCE provides high quality images of the GI tract, evaluation is limited to the mucosal surface. This work investigates feasibility and design considerations for wireless capsule endoscopic ultrasound (WCEU) that combines the benefits of WCE and ultrasound imaging. This work has two goals: (1) evaluate transducer designs appropriate for WCEU and (2) investigate whether peristalsis can produce sufficient contact to ensure acoustic coupling. Between mechanical scanning (MS) and side-looking array (SLA) designs, MS performs better for both imaging performance and system complexity. In vivo imaging in pigs demonstrates promising results, although the effect of peristalsis and resulting coverage needs further investigation and quantification.","author":[{"dropping-particle":"","family":"Lee","given":"John H.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Traverso","given":"Giovanni","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schoellhammer","given":"Carl M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Blankschtein","given":"Daniel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Langer","given":"Robert","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Thomenius","given":"Kai E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Boning","given":"Duane S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Anthony","given":"Brian W.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"2014 IEEE International Ultrasonics Symposium","id":"ITEM-3","issued":{"date-parts":[["2014","9"]]},"page":"734-737","publisher":"IEEE","title":"Towards wireless capsule endoscopic ultrasound (WCEU)","title-short":"Ultrasonics Symposium (IUS), 2014 IEEE Internation","type":"paper-conference"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>4,61,64</sup>","plainTextFormattedCitation":"4,61,64","previouslyFormattedCitation":"<sup>4,61,64</sup>"},"properties":{"noteIndex":0},"schema":""}4,61,64. Concurrently, Qiu et al. have investigated a mechanical approach using a single-element transducer [G] actuated by an oscillating motor that enables radial imaging of the gut wallADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/TMI.2017.2699973","ISBN":"2014061015185","ISSN":"0278-0062","author":[{"dropping-particle":"","family":"Wang","given":"Xingying","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Seetohul","given":"Vipin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chen","given":"Ruimin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zhang","given":"Zhiqiang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Qian","given":"Ming","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shi","given":"Zhehao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yang","given":"Ge","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mu","given":"Peitian","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wang","given":"Congzhi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Huang","given":"Zhihong","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zhou","given":"Qifa","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zheng","given":"Hairong","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cochran","given":"Sandy","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Qiu","given":"Weibao","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Transactions on Medical Imaging","id":"ITEM-1","issue":"9","issued":{"date-parts":[["2017","9"]]},"page":"1922-1929","title":"Development of a Mechanical Scanning Device With High-Frequency Ultrasound Transducer for Ultrasonic Capsule Endoscopy","type":"article-journal","volume":"36"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>61</sup>","plainTextFormattedCitation":"61","previouslyFormattedCitation":"<sup>61</sup>"},"properties":{"noteIndex":0},"schema":""}61. Transducer frequency makes an important contribution to USCE function through its strong effect on image resolution (two-point discrimination) and depth of penetration. Conventional EUS typically employs ultrasound frequencies in the range 5–18 MHz, corresponding to axial resolutions of ~0.2–0.8 mm and depths of ~2–8 cm, respectivelyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/B978-0-323-06397-5.00072-1","ISBN":"9780323063975","author":[{"dropping-particle":"","family":"McNally","given":"Peter R.","non-dropping-particle":"","parse-names":false,"suffix":""}],"chapter-number":"72","container-title":"GI/Liver Secrets","edition":"Fourth","editor":[{"dropping-particle":"","family":"McNally","given":"Peter R.","non-dropping-particle":"","parse-names":false,"suffix":""}],"id":"ITEM-1","issued":{"date-parts":[["2010"]]},"page":"537-544","publisher":"Elsevier","title":"Endoscopic Ultrasound","type":"chapter"},"uris":["",""]}],"mendeley":{"formattedCitation":"<sup>67</sup>","plainTextFormattedCitation":"67","previouslyFormattedCitation":"<sup>67</sup>"},"properties":{"noteIndex":0},"schema":""}67. Lower frequencies (5-20 MHz) canmay enable imaging of organs located beyond the wall of the gastrointestinal tract, whereas higher frequencies (>25 MHz) can may provide more detailed images of the gut wall. Higher frequencies are employed when staging local tumour burden using a tumuor-node-metastatis (TNM)TNM (Tumor, Node, Metastasis) classification system, as they enable reliable means of determining tumour size and invasive extent (T stage) as well as proximal lymph node spread (N stage)ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/codi.12445","ISBN":"1462-8910","ISSN":"14628910","abstract":"Aim: With an increasing array of treatment modalities available for colon cancer, it is increasingly important to stage tumours accurately to allocate the appropriate management. This study evaluated the accuracy of mini-probe endoscopic ultrasound (EUS) in assigning clinical stage to colon cancer. Method: An electronic search was performed in January 2013 using the Embase, MEDLINE and Cochrane databases. This was supplemented by a hand search of published abstracts from scientific meetings. Trials evaluating the accuracy of the mini-probe EUS compared with histopathological grade in determining the clinical stage of colon cancer were included in this pooled analysis. The main outcome measures included accuracy, sensitivity and specificity for T and N staging. Results: Ten studies were identified which compared the mini-probe EUS staging of 642 colon or rectal cancers with the histopathological specimen. The pooled sensitivity and specificity for staging were 0.91 and 0.98 for T1 tumours, 0.78 and 0.94 for T2 tumours, 0.97 and 0.90 for T3/T4 tumours and 0.63 and 0.82 for nodal staging. Eight per cent of T1/T2 tumours were upstaged to T3/T4 tumours and 5% of T3/T4 tumours were downstaged. Conclusion: Mini-probe EUS is highly effective for assigning clinical stage in colon cancer and in identifying patients who may be suitable for nonsurgical treatment including neoadjuvant chemotherapy or endoscopic resection. ? 2013 The Association of Coloproctology of Great Britain and Ireland.","author":[{"dropping-particle":"","family":"Gall","given":"T. M. H.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Markar","given":"S. 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The aim of this study was to investigate the role of high-frequency miniprobe endoscopic ultrasound (EUS) for therapeutic decisions making in patients with gastric or colonic tumors. METHODS: A total of 137 patients underwent EUS with a 12.5-MHz miniprobe for preoperative staging of tumors of the stomach ( n = 49) or colon ( n = 88). After resection, the surgical path was reviewed to analyze the role of preoperative staging with miniprobes. RESULTS: Miniprobe EUS enabled accurate assessment of the infiltration depth of gastric and colonic tumors. The overall accuracy rates were 88% and 87%, respectively. The lymph node status was predicted correctly in 82% of the patients (sensitivity, 61%, specificity, 94%). Based on the results of miniprobe EUS, patients with gastric cancer were accurately selected to undergo endoscopic mucosal resection, laparoscopic resection, or open surgery in 100%, 91%, and 86% of the cases, respectively. In patients with colonic tumors, the treatment decision analysis showed that the stratification was correct in 90% of the patients. CONCLUSIONS: Miniprobe EUS is a reliable method for validating treatment decisions for patients undergoing minimally invasive procedures for gastric and colonic tumors. This method is particularly valuable in the management of colon cancer, because endoscopic and laparoscopic resections can be offered to selected patients as an alternative to open surgery.","author":[{"dropping-particle":"","family":"Hünerbein","given":"M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Handke","given":"T.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ulmer","given":"C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schlag","given":"P. M.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Surgical Endoscopy and Other Interventional Techniques","id":"ITEM-2","issued":{"date-parts":[["2004"]]},"title":"Impact of miniprobe ultrasonography on planning of minimally invasive surgery for gastric and colonic tumors","type":"article"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1055/s-2005-870142","ISBN":"0013-726X (Print)\\r0013-726X (Linking)","ISSN":"0013726X","PMID":"16032488","abstract":"BACKGROUND AND STUDY AIMS: Miniprobe ultrasound technology allows in-vivo luminal staging of colorectal cancer with a probe that passes directly through the colonoscope's instrument port. Conventional rigid radial echoscopes are limited by the need for a second examination, an inability to image stenotic lesions, and the inaccessibility of proximal tumours. Since minimally invasive resection techniques are now possible, a sensitive preoperative staging tool is needed to optimize patient selection. The aim of this study was to examine the accuracy of miniprobe ultrasound imaging in the preoperative staging of colorectal cancer and to examine the value of the technique for management decisions., PATIENTS AND METHODS: In a prospective study, a total of 131 consecutive patients with adenocarcinoma or broad-based polyps of the colorectum underwent 12.5-MHz miniprobe ultrasonography examinations conducted by a single endoscopist. Staging criteria for depth of tumour infiltration and nodal status were determined. Nodal disease was defined as the presence of a hypoechoic, round, defined boundary lesion larger than 10 mm in diameter. T0-T1N0 lesions were resected using endoscopic mucosal resection, and patients with lesions staged as T2N1 were referred for surgical resection. Tumour staging using endoscopic ultrasonography was then compared with the histopathological specimens., RESULTS: The accuracy of T staging using endoscopic ultrasonography was 96 % in comparison with the histopathological specimen. Five lesions (4 %) were incorrectly overstaged as T3 - pathology stage T2. Understaging occurred in three lesions (endoscopic ultrasound stage T3 - pathology stage T4). The overall accuracy of nodal staging using endoscopic ultrasonography was 87 % (sensitivity 0.95, specificity 0.71, positive predictive value 0.87, negative predictive value 0.88)., CONCLUSIONS: Miniprobe ultrasonography has a high overall accuracy for both T staging and N staging of colorectal cancer and may have an important role in selecting patients suitable for minimally invasive resection techniques.","author":[{"dropping-particle":"","family":"Hurlstone","given":"D. P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Brown","given":"S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cross","given":"S. S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shorthouse","given":"A. J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sanders","given":"D. S.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Endoscopy","id":"ITEM-3","issued":{"date-parts":[["2005"]]},"title":"Endoscopic ultrasound miniprobe staging of colorectal cancer: Can management be modified?","type":"article-journal"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>68–70</sup>","plainTextFormattedCitation":"68–70","previouslyFormattedCitation":"<sup>68–70</sup>"},"properties":{"noteIndex":0},"schema":""}68–70. ?US miniprobes introduced via the biopsy channel of conventional endoscopes for CRC staging have improved axial and lateral image resolution with higher than conventional EUS frequenciesADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/codi.12445","ISBN":"1462-8910","ISSN":"14628910","abstract":"Aim: With an increasing array of treatment modalities available for colon cancer, it is increasingly important to stage tumours accurately to allocate the appropriate management. This study evaluated the accuracy of mini-probe endoscopic ultrasound (EUS) in assigning clinical stage to colon cancer. Method: An electronic search was performed in January 2013 using the Embase, MEDLINE and Cochrane databases. This was supplemented by a hand search of published abstracts from scientific meetings. Trials evaluating the accuracy of the mini-probe EUS compared with histopathological grade in determining the clinical stage of colon cancer were included in this pooled analysis. The main outcome measures included accuracy, sensitivity and specificity for T and N staging. Results: Ten studies were identified which compared the mini-probe EUS staging of 642 colon or rectal cancers with the histopathological specimen. The pooled sensitivity and specificity for staging were 0.91 and 0.98 for T1 tumours, 0.78 and 0.94 for T2 tumours, 0.97 and 0.90 for T3/T4 tumours and 0.63 and 0.82 for nodal staging. Eight per cent of T1/T2 tumours were upstaged to T3/T4 tumours and 5% of T3/T4 tumours were downstaged. Conclusion: Mini-probe EUS is highly effective for assigning clinical stage in colon cancer and in identifying patients who may be suitable for nonsurgical treatment including neoadjuvant chemotherapy or endoscopic resection. ? 2013 The Association of Coloproctology of Great Britain and Ireland.","author":[{"dropping-particle":"","family":"Gall","given":"T. M. H.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Markar","given":"S. R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jackson","given":"D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Haji","given":"A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Faiz","given":"O.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Colorectal Disease","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2014"]]},"page":"O1-O8","title":"Mini-probe ultrasonography for the staging of colon cancer: a systematic review and meta-analysis","type":"article-journal","volume":"16"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1097/01.mcg.0000170736.51510.12","ISSN":"0192-0790","PMID":"16000920","author":[{"dropping-particle":"","family":"Schembre","given":"Drew","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ayub","given":"Kamran","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jiranek","given":"Geoffrey","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Clinical Gastroenterology","id":"ITEM-2","issue":"7","issued":{"date-parts":[["2005","8"]]},"page":"555-556","title":"High-Frequency Mini-Probe Ultrasound: The Rodney Dangerfield of Endoscopy?","type":"article-journal","volume":"39"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1109/ULTSYM.2015.0304","ISBN":"978-1-4799-8182-3","abstract":"Capsule endoscopy represents a highly convenient but limited means of imaging inflammatory conditions of the small bowel. The inclusion of high frequency microultrasound into a capsule endoscope has the potential to enhance diagnostic capabilities with subsurface imaging of the bowel wall. Experimental studies on abattoir-obtained porcine small bowel have been carried out as an ethical means to characterize healthy and altered tissue in a preclinical setting as well as to explore other means of imaging pathology. Samples of small bowel were cannulated and perfused with phosphate buffered saline followed by variable dilutions of polystyrene microspheres. All samples were scanned with a purpose built step scanner employing a 47 MHz single element transducer. Results indicated that tissue high frequency ultrasound demonstrated sufficient sensitivity to detect the disruption normal histology with microsphere infusion. The combination of microultrasound and capsule endoscopy has the potential to enhance the diagnostic capabilities with improved qualitative and quantitative dimensions.","author":[{"dropping-particle":"","family":"Cox","given":"Benjamin F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Seetohul","given":"Vipin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lay","given":"Holly","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cochran","given":"Sandy","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"2015 IEEE International Ultrasonics Symposium (IUS)","id":"ITEM-3","issued":{"date-parts":[["2015","10"]]},"page":"1-4","publisher":"IEEE","title":"Microultraound and small bowel inflammation: Tissue phantom studies","type":"paper-conference"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>68,71,72</sup>","plainTextFormattedCitation":"68,71,72","previouslyFormattedCitation":"<sup>68,71,72</sup>"},"properties":{"noteIndex":0},"schema":""}68,71,72. These higher frequencies result in highly detailed subsurface information that includes structural and cellular tissue composition. Additionally, there is a simultaneous decrease in the depth of tissue penetration as the frequency is increased, which has the potential to mitigate confounding information (for example, adjacent bowel loops versus edema) caused by deep penetrating soundwaves at standard frequencies in the 5-20 MHz rangeADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.3748/wjg.v17.i27.3192","ISBN":"4991318535000","ISSN":"10079327","PMID":"21912467","abstract":"Diagnosis of chronic inflammatory bowel diseases (IBD) is based on a combination of clinical symptoms, laboratory tests and imaging data. Imaging of the morphological characteristics of IBD includes the assessment of mucosal alterations, transmural involvement and extraintestinal manifestations. No single imaging technique serves as a diagnostic gold standard to encompass all disease manifestations. Ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) allow cross-sectional imaging of the transmural alterations and extraintestinal manifestations. While in the USA the technique of choice is CT, in Europe the focus is more on MRI and ultrasound (US). Most patients with chronic IBD are diagnosed at a young age. After baseline diagnosis many of these young patients have to undergo repetitive imaging procedures during the variable clinical course of the disease, characterized by alternate periods of remission and active disease, and in monitoring the response to treatment. US has the advantage of being noninvasive, less costly, and easily repeatable, and thus can be very useful in following up patients with IBD. In addition, rising concern about radiation exposure in young adults indicates the demand for radiation-sparing techniques like US and MRI. This article focuses on the current clinical practice of US in IBD, describing the current technologies used in transabdominal intestinal US and the characteristic sonographic findings in Crohn?s disease and ulcerative colitis.","author":[{"dropping-particle":"","family":"Strobel","given":"Deike","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Goertz","given":"Ruediger S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bernatik","given":"Thomas","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"World Journal of Gastroenterology","id":"ITEM-1","issue":"27","issued":{"date-parts":[["2011","7"]]},"page":"3192-3197","title":"Diagnostics in inflammatory bowel disease: Ultrasound","type":"article-journal","volume":"17"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>73</sup>","plainTextFormattedCitation":"73","previouslyFormattedCitation":"<sup>73</sup>"},"properties":{"noteIndex":0},"schema":""}73. The Qiu and Cochran groups are investigatinginvestigated the potential benefit of high frequency (>25 MHz) ultrasound ultrasonography for high resolution, known as μUS, in their respective capsules. Cochran has demonstrated the potential of a capsule with multiple single-element ultrasonic transducers operating at 30 MHz in imaging the layers constituting the small bowelADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/TBME.2018.2852715","ISSN":"0018-9294","author":[{"dropping-particle":"","family":"Lay","given":"Holly","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cummins","given":"Gerard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cox","given":"Benjamin F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Qiu","given":"Yongqiang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Turcanu","given":"Mihnea Vlad","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"McPhillips","given":"Rachael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Connor","given":"Ciaran","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gregson","given":"Rachael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Clutton","given":"Eddie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Desmulliez","given":"Marc P.Y.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cochran","given":"Sandy","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Transactions on Biomedical Engineering","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2018"]]},"page":"632 - 639","title":"In-Vivo Evaluation of Microultrasound and Thermometric Capsule Endoscopes","type":"article-journal","volume":"66"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>4</sup>","plainTextFormattedCitation":"4","previouslyFormattedCitation":"<sup>4</sup>"},"properties":{"noteIndex":0},"schema":""}4. Although USCE is in its early stages, the principle of submucosal bowel wall imaging is attractive as USCE will enable deeper tissue analysis with the potential of detecting transmural inflammation and thus has the capability to assess disease activity in Crohn’s disease. [H3]Autofluorescence imaging Autofluorescence imaging (AFI) uses short wavelengths of light, typically 380–500 nm, to illuminate tissue, exciting either endogenous or exogenous fluorophores to differentiate healthy and malignant tissue. The incident light absorbed by the tissue causes the fluorophores to emit light at longer wavelengths, typically 490–590?nm. One study has shown that autofluorescence is reduced by a factor of 3 to 12 in malignant tissue compared with healthy tissueADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.3892/ijo.24.1.59","PMID":"14654941","author":[{"dropping-particle":"","family":"Huang","given":"Z.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zheng","given":"W.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Xie","given":"S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chen","given":"R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zeng","given":"H.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"McLean","given":"D.I.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lui","given":"H.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"International Journal of Oncology","id":"ITEM-1","issued":{"date-parts":[["2004"]]},"page":"59-63","title":"Laser-induced autofluorescence microscopy of normal and tumor human colonic tissue","type":"article-journal","volume":"24"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>74</sup>","plainTextFormattedCitation":"74","previouslyFormattedCitation":"<sup>74</sup>"},"properties":{"noteIndex":0},"schema":""}74. Various studies have compared the efficacy of conventional AFI endoscopy to that of conventional WLI endoscopy for the detection of gastrointestinal disease. Several of these studies have shown that AFI increases the detection rate of diseases such as colorectal adenomaADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1186/1471-230X-12-75","ISBN":"1471-230X (Electronic)\\r1471-230X (Linking)","ISSN":"1471230X","PMID":"22726319","abstract":"Some patients under close colonoscopic surveillance still develop colorectal cancer, thus suggesting the overlook of colorectal adenoma by endoscopists. AFI detects colorectal adenoma as a clear magenta, therefore the efficacy of AFI is expected to improve the detection ability of colorectal adenoma. The aim of this study is to determine the efficacy of AFI in detecting colorectal adenoma.","author":[{"dropping-particle":"","family":"Moriichi","given":"Kentaro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fujiya","given":"Mikihiro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sato","given":"Ryu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Watari","given":"Jiro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nomura","given":"Yoshiki","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nata","given":"Toshie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ueno","given":"Nobuhiro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Maeda","given":"Shigeaki","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kashima","given":"Shin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Itabashi","given":"Kentaro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ishikawa","given":"Chisato","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Inaba","given":"Yuhei","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ito","given":"Takahiro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Okamoto","given":"Kotaro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tanabe","given":"Hiroki","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mizukami","given":"Yusuke","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Saitoh","given":"Yusuke","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kohgo","given":"Yutaka","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"BMC Gastroenterology","id":"ITEM-1","issued":{"date-parts":[["2012"]]},"title":"Back-to-Back Comparison of Auto-Fluorescence Imaging (AFI) Versus High Resolution White Light Colonoscopy for Adenoma Detection","type":"article-journal","volume":"12"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>75</sup>","plainTextFormattedCitation":"75","previouslyFormattedCitation":"<sup>75</sup>"},"properties":{"noteIndex":0},"schema":""}75 and polypsADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1055/s-0034-1391708","ISBN":"2364-3722 (Print)\\r2196-9736","ISSN":"2364-3722","PMID":"26171435","abstract":"BACKGROUND AND STUDY AIMS: Autofluorescence imaging (AFI) is an endoscopic imaging technique used to increase the detection of premalignant gastrointestinal lesions, and it has gradually become popular in recent years. This meta-analysis was performed to examine whether AFI provides greater efficacy in the detection of adenomatous and polypoid lesions and can even prevent the failure to detect a single adenoma or polyp.?The aim of the study was to systematically review the efficacy of AFI in increasing detection rates and decreasing miss rates.\\n\\nMETHODS: Pertinent articles were identified through a search of databases up to December 2013 that included patients who had undergone two same-day colonoscopies (AFI and white light endoscopy [WLE]), followed by polypectomy. Fixed and random effects models were used to detect significant differences between AFI and WLE in regard to adenoma detection rate (ADR), polyp detection rate (PDR), adenoma miss rate (AMR), polyp miss rate (PMR), and procedural time.\\n\\nRESULTS: A total of 1199 patients from six eligible studies met the inclusion criteria. No significant differences were found in ADR (odds ratio [OR] 1.01; 95?% confidence interval [95?%CI] 0.74?-?1.37), PDR (OR 0.86; 95?%CI 0.57?-?1.30), or advanced ADR (OR 1.22; 95?%CI 0.69?-?2.17). The AMR (OR 0.62; 95?%CI 0.44?-?0.86) and PMR (OR 0.64; 95?%CI 0.48?-?0.85) by AFI were significantly lower than those by WLE. The procedural time of AFI was significantly longer than that of WLE (mean 8.00 minutes; 95?%CI 1.59?-?14.41). Subgroup meta-analysis for the other characteristics was not performed because of insufficiency of the primary data.\\n\\nCONCLUSIONS: AFI decreases AMR and PMR significantly compared with WLE but does not improve ADR or PDR. AMR and PMR may be decreased by using AFI in flat and small lesions or when less experienced endoscopists perform the procedure.","author":[{"dropping-particle":"","family":"Zhao","given":"Zi-Ye","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Guan","given":"Yu-Gen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Li","given":"Bai-Rong","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shan","given":"Yong-Qi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yan","given":"Fei-Hu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gao","given":"Yong-Jun-Yi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wang","given":"Hao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lou","given":"Zheng","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fu","given":"Chuang-Gang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yu","given":"En-Da","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Endoscopy International Open","id":"ITEM-1","issue":"03","issued":{"date-parts":[["2015"]]},"page":"E226-E235","title":"Detection and miss rates of autofluorescence imaging of adenomatous and polypoid lesions during colonoscopy: a systematic review and meta-analysis","type":"article-journal","volume":"3"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>76</sup>","plainTextFormattedCitation":"76","previouslyFormattedCitation":"<sup>76</sup>"},"properties":{"noteIndex":0},"schema":""}76 compared with WLIADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1007/s12328-016-0658-3","ISSN":"1865-7265","PMID":"27294612","abstract":"Image-enhanced endoscopy (IEE) has been developed and is applied in the clinical setting throughout the world. Most reports regarding IEE have evaluated the efficacy of narrow-band imaging (NBI) in the diagnosis of gastrointestinal disorders. Although autofluorescence imaging (AFI) is a form of IEE, its usefulness remains unclear. The present review focused on the efficacy of AFI in the diagnosis of colorectal disease, particularly neoplasia and ulcerative colitis (UC). AFI-based diagnoses are made via the subjective judgment of the color on the monitor. The efficacy of AFI in detection and differentiation in patients with colorectal neoplastic lesions remains controversial, which may be dependent on the study design and the diagnostic procedures. Although the number of the reports related to UC is very small, most suggest that AFI is effective in UC patients. AFI is distinct from other modalities in that it can quantitatively assess the lesion based on the fluorescence intensity without any morphological assessments. AFI could be useful for patients with colorectal disease.","author":[{"dropping-particle":"","family":"Moriichi","given":"Kentaro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fujiya","given":"Mikihiro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Okumura","given":"Toshikatsu","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Clinical journal of gastroenterology","id":"ITEM-1","issue":"4","issued":{"date-parts":[["2016","8"]]},"page":"175-83","title":"The efficacy of autofluorescence imaging in the diagnosis of colorectal diseases.","type":"article-journal","volume":"9"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1186/1471-230X-12-75","ISBN":"1471-230X (Electronic)\\r1471-230X (Linking)","ISSN":"1471230X","PMID":"22726319","abstract":"Some patients under close colonoscopic surveillance still develop colorectal cancer, thus suggesting the overlook of colorectal adenoma by endoscopists. AFI detects colorectal adenoma as a clear magenta, therefore the efficacy of AFI is expected to improve the detection ability of colorectal adenoma. The aim of this study is to determine the efficacy of AFI in detecting colorectal adenoma.","author":[{"dropping-particle":"","family":"Moriichi","given":"Kentaro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fujiya","given":"Mikihiro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sato","given":"Ryu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Watari","given":"Jiro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nomura","given":"Yoshiki","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nata","given":"Toshie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ueno","given":"Nobuhiro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Maeda","given":"Shigeaki","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kashima","given":"Shin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Itabashi","given":"Kentaro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ishikawa","given":"Chisato","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Inaba","given":"Yuhei","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ito","given":"Takahiro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Okamoto","given":"Kotaro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tanabe","given":"Hiroki","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mizukami","given":"Yusuke","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Saitoh","given":"Yusuke","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kohgo","given":"Yutaka","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"BMC Gastroenterology","id":"ITEM-2","issued":{"date-parts":[["2012"]]},"title":"Back-to-Back Comparison of Auto-Fluorescence Imaging (AFI) Versus High Resolution White Light Colonoscopy for Adenoma Detection","type":"article-journal","volume":"12"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1055/s-0034-1391708","ISBN":"2364-3722 (Print)\\r2196-9736","ISSN":"2364-3722","PMID":"26171435","abstract":"BACKGROUND AND STUDY AIMS: Autofluorescence imaging (AFI) is an endoscopic imaging technique used to increase the detection of premalignant gastrointestinal lesions, and it has gradually become popular in recent years. This meta-analysis was performed to examine whether AFI provides greater efficacy in the detection of adenomatous and polypoid lesions and can even prevent the failure to detect a single adenoma or polyp.?The aim of the study was to systematically review the efficacy of AFI in increasing detection rates and decreasing miss rates.\\n\\nMETHODS: Pertinent articles were identified through a search of databases up to December 2013 that included patients who had undergone two same-day colonoscopies (AFI and white light endoscopy [WLE]), followed by polypectomy. Fixed and random effects models were used to detect significant differences between AFI and WLE in regard to adenoma detection rate (ADR), polyp detection rate (PDR), adenoma miss rate (AMR), polyp miss rate (PMR), and procedural time.\\n\\nRESULTS: A total of 1199 patients from six eligible studies met the inclusion criteria. No significant differences were found in ADR (odds ratio [OR] 1.01; 95?% confidence interval [95?%CI] 0.74?-?1.37), PDR (OR 0.86; 95?%CI 0.57?-?1.30), or advanced ADR (OR 1.22; 95?%CI 0.69?-?2.17). The AMR (OR 0.62; 95?%CI 0.44?-?0.86) and PMR (OR 0.64; 95?%CI 0.48?-?0.85) by AFI were significantly lower than those by WLE. The procedural time of AFI was significantly longer than that of WLE (mean 8.00 minutes; 95?%CI 1.59?-?14.41). Subgroup meta-analysis for the other characteristics was not performed because of insufficiency of the primary data.\\n\\nCONCLUSIONS: AFI decreases AMR and PMR significantly compared with WLE but does not improve ADR or PDR. AMR and PMR may be decreased by using AFI in flat and small lesions or when less experienced endoscopists perform the procedure.","author":[{"dropping-particle":"","family":"Zhao","given":"Zi-Ye","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Guan","given":"Yu-Gen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Li","given":"Bai-Rong","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shan","given":"Yong-Qi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yan","given":"Fei-Hu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gao","given":"Yong-Jun-Yi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wang","given":"Hao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lou","given":"Zheng","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fu","given":"Chuang-Gang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yu","given":"En-Da","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Endoscopy International Open","id":"ITEM-3","issue":"03","issued":{"date-parts":[["2015"]]},"page":"E226-E235","title":"Detection and miss rates of autofluorescence imaging of adenomatous and polypoid lesions during colonoscopy: a systematic review and meta-analysis","type":"article-journal","volume":"3"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>75–77</sup>","plainTextFormattedCitation":"75–77","previouslyFormattedCitation":"<sup>75–77</sup>"},"properties":{"noteIndex":0},"schema":""}75–77. The efficacy of AFI in diagnosing IBDs such as ulcerative colitis has also been examined. Studies have shown a correlation between the intensity of AFI images and the severity of the inflammationADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/j.1443-1661.2007.00725.x","ISSN":"09155635","abstract":"The efficacy of autofluorescence imaging (AFI) for assessing ulcerative colitis (UC) activity was reviewed. AFI images of UC lesions could be classified into four categories: green; green with purple spots; purple with green spots; and purple.The strength of purple inAFI images of UC lesions is related to histologic severity, thus this classification is helpful to assess the activity of UC. The autofluorescence of AFI images was also quantified using color analysis software.Active lesions had significantly low autofluorescence/reflex ratio than inactive areas in UC patients. The ratio is inversely proportional to histologic severity.When the cut-off is 0.9, the accuracy to predict histologic activity by AFI is 92%.","author":[{"dropping-particle":"","family":"Fujiya","given":"Mikihiro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Saitoh","given":"Yusuke","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Watari","given":"Jiro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Moriichi","given":"Kentaro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kohgo","given":"Yutaka","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Digestive Endoscopy","id":"ITEM-1","issue":"SUPPL. 1","issued":{"date-parts":[["2007"]]},"page":"145-149","title":"Autofluorescence imaging is useful to assess activity of ulcerative colitis","type":"article-journal","volume":"19"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.3748/wjg.v17.i46.5110","ISBN":"1007-9327 (Print)\\r1007-9327 (Linking)","ISSN":"10079327","PMID":"22171146","abstract":"AIM: To validate the clinical relevance of autofluorescence imaging (AFI) endoscopy for the assessment of inflammatory ulcerative colitis (UC).\\n\\nMETHODS: A total of 572 endoscopic images were selected from 42 UC patients: 286 taken with white light imaging (WLI) and 286 with AFI from the same sites. WLI images were assessed for overall mucosal inflammation according to Mayo endoscopic subscore (MES), and for seven characteristic endoscopic features. Likewise, AFI photographs were scored according to relative abundance of red, green and blue color components within each image based on an RGB additive color model. WLI and AFI endoscopic scores from the same sites were compared. Histological evaluation of biopsies was according to the Riley Index.\\n\\nRESULTS: Relative to red (r = 0.52, P < 0.01) or blue (r = 0.56, P < 0.01) color component, the green color component of AFI (r = -0.62, P < 0.01) corresponded more closely with mucosal inflammation sites. There were significant differences in green color components between MES-0 (0.396 ± 0.043) and MES-1 (0.340 ± 0.035) (P < 0.01), and between MES-1 and ≥ MES-2 (0.318 ± 0.037) (P < 0.01). The WLI scores for \"vascular patterns\" (r = -0.65, P < 0.01), \"edema\" (r = -0.62, P < 0.01), histology scores for \"polymorphonuclear cells in the lamina propria\" (r = -0.51, P < 0.01) and \"crypt architectural irregularities\" (r = -0.51, P < 0.01) showed correlation with the green color component of AFI. There were significant differences in green color components between limited (0.399 ± 0.042) and extensive (0.375 ± 0.044) (P = 0.014) polymorphonuclear cell infiltration within MES-0. As the severity of the mucosal inflammation increased, the green color component of AFI decreased. The AFI green color component was well correlated with the characteristic endoscopic and histological inflammatory features of UC.\\n\\nCONCLUSION: AFI has application in detecting inflammatory lesions, including microscopic activity in the colonic mucosa of UC patients, based on the green color component of images.","author":[{"dropping-particle":"","family":"Osada","given":"Taro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Arakawa","given":"Atsushi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sakamoto","given":"Naoto","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ueyama","given":"Hiroya","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shibuya","given":"Tomoyoshi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ogihara","given":"Tatsuo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yao","given":"Takashi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Watanabe","given":"Sumio","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"World Journal of Gastroenterology","id":"ITEM-2","issue":"46","issued":{"date-parts":[["2011"]]},"page":"5110-5116","title":"Autofluorescence imaging endoscopy for identification and assessment of inflammatory ulcerative colitis","type":"article-journal","volume":"17"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>78,79</sup>","plainTextFormattedCitation":"78,79","previouslyFormattedCitation":"<sup>78,79</sup>"},"properties":{"noteIndex":0},"schema":""}78,79, with intensity shown to be a useful marker of active inflammation in ulcerative colitisADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1007/s00384-015-2332-5","ISSN":"14321262","PMID":"26264047","abstract":"BACKGROUND AND AIMS: No endoscopic examination has been able to evaluate severity of ulcerative colitis (UC) by quantification. This prospective study investigated the efficacy of quantifying autofluorescence imaging (AFI) to assess the severity of UC, which captures the fluorescence emitted from intestinal tissue and then quantifies the intensity using an image-analytical software program.\\n\\nMATERIALS AND METHODS: Eleven endoscopists separately evaluated 135 images of conventional endoscopy (CE) and AFI from a same lesion. A CE image corresponding to Mayo endoscopic subscore 0 or 1 was defined as being inactive. The fluorescence intensities of AFI were quantified using an image-analytical software program (F index; FI). Active inflammation was defined when Matts' histological grade was 2 or more. A cut-off value of the FI for active inflammation was determined using a receiver operating characteristic (ROC) analysis. The inter-observer consistency was calculated by unweighted kappa statistics.\\n\\nRESULTS: The correlation coefficient for the FI was inversely related to the histological severity (r?=?-0.558, p?<?0.0001). The ROC analysis showed that the optimal cut-off value for the FI for active inflammation was 0.906. The average diagnostic accuracy of the FI was significantly higher than those of the CE (84.7 vs 78.5?%, p?<?0.01). The kappa values for the inter-observer consistency of CE and the FI were 0.60 and 0.95 in all participants, 0.53 and 0.97 in the less-experienced endoscopists group and 0.67 and 0.93 in the expert group, respectively.\\n\\nCONCLUSIONS: The quantified AFI is considered to be an accurate and objective indicator that can be used to assess the activity of ulcerative colitis, particularly for less-experienced endoscopists.","author":[{"dropping-particle":"","family":"Moriichi","given":"Kentaro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fujiya","given":"Mikihiro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ijiri","given":"Masami","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tanaka","given":"Kazuyuki","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sakatani","given":"Aki","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dokoshi","given":"Tatsuya","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fujibayashi","given":"Shugo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ando","given":"Katsuyoshi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nomura","given":"Yoshiki","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ueno","given":"Nobuhiro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kashima","given":"Shin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gotoh","given":"Takuma","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sasajima","given":"Junpei","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Inaba","given":"Yuhei","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ito","given":"Takahiro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tanabe","given":"Hiroki","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Saitoh","given":"Yusuke","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kohgo","given":"Yutaka","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"International Journal of Colorectal Disease","id":"ITEM-1","issue":"12","issued":{"date-parts":[["2015"]]},"page":"1639-1643","title":"Quantification of autofluorescence imaging can accurately and objectively assess the severity of ulcerative colitis","type":"article-journal","volume":"30"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>80</sup>","plainTextFormattedCitation":"80","previouslyFormattedCitation":"<sup>80</sup>"},"properties":{"noteIndex":0},"schema":""}80. Because of this potential, there is considerable research interest in the use of AFI with conventional endoscopy, so it was logical that the integration of AFI with CE would be explored to improve the diagnostic capabilities of CE. The integration of AFI CE has led to the development of several prototype imaging devices such as those being created by the Cummings groupADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1038/srep18591","ISSN":"2045-2322","PMID":"26678456","abstract":"Fluorescence Imaging (FI) is a powerful technique in biological science and clinical medicine. Current FI devices that are used either for in-vivo or in-vitro studies are expensive, bulky and consume substantial power, confining the technique to laboratories and hospital examination rooms. Here we present a miniaturised wireless fluorescence endoscope capsule with low power consumption that will pave the way for future FI systems and applications. With enhanced sensitivity compared to existing technology we have demonstrated that the capsule can be successfully used to image tissue autofluorescence and targeted fluorescence via fluorophore labelling of tissues. The capsule incorporates a state-of-the-art complementary metal oxide semiconductor single photon avalanche detector imaging array, miniaturised optical isolation, wireless technology and low power design. When in use the capsule consumes only 30.9 mW, and deploys very low-level 468 nm illumination. The device has the potential to replace highly power-hungry intrusive optical fibre based endoscopes and to extend the range of clinical examination below the duodenum. To demonstrate the performance of our capsule, we imaged fluorescence phantoms incorporating principal tissue fluorophores (flavins) and absorbers (haemoglobin). We also demonstrated the utility of marker identification by imaging a 20 μM fluorescein isothiocyanate (FITC) labelling solution on mammalian tissue.","author":[{"dropping-particle":"","family":"Al-Rawhani","given":"Mohammed A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Beeley","given":"James","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cumming","given":"David R. S.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Scientific Reports","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2015","11","18"]]},"page":"18591","publisher":"The Author(s)","title":"Wireless fluorescence capsule for endoscopy using single photon-based detection","type":"article-journal","volume":"5"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>81</sup>","plainTextFormattedCitation":"81","previouslyFormattedCitation":"<sup>81</sup>"},"properties":{"noteIndex":0},"schema":""}81, and has also contributed use of fluorescence as a sensing modality as evidenced by the work of Demosthenous et al.ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/TBCAS.2015.2449277","ISBN":"1932-4545 VO - 10","ISSN":"1932-4545","abstract":"Infrared fluorescence endoscopy (IRFE), in conjunction with an infrared fluorescent-labelling contrast agent, is a well known technique used for efficient early-stage cancer detection. In this paper we present a cost-effective ( $500) screening capsule prototype, which is able to detect infrared (IR) fluorescence emitted by indocyanine green (ICG) fluorophore dye. Rather than image, the capsule works as a high-sensitivity fluorometer that records fluorescence levels throughout the small intestine. The presented mixed-signal system has a small size, consumes very little power ( ≈ 6.3 mA) and does not require an external belt and hardware for data collection. By determining fluorescence levels in the intestine, rather than collecting images, we avoid the need for labour intensive video analysis. The whole system is contained within a compact ingestible capsule, that is sized so as to come into close contact with the intestine walls during peristalsis. Ex-vivo experiments, on ICG-impregnated swine intestine, have shown that the prototype system is able to detect low concentrations of ICG in the nanomolar and micromolar region, which is required to detect early cancer in the small intestine.","author":[{"dropping-particle":"","family":"Demosthenous","given":"Panayiota","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pitris","given":"Constantinos","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Georgiou","given":"Julius","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Transactions on Biomedical Circuits and Systems","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2016","4"]]},"page":"467-476","title":"Infrared Fluorescence-Based Cancer Screening Capsule for the Small Intestine","type":"article-journal","volume":"10"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>82</sup>","plainTextFormattedCitation":"82","previouslyFormattedCitation":"<sup>82</sup>"},"properties":{"noteIndex":0},"schema":""}82 and Nemiroski et al.ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1039/C5LC00770D","ISBN":"1473-0197","ISSN":"1473-0197","PMID":"26490455","abstract":"A swallowable, capsular fluorometer simplifies detection of upper gastrointestinal bleeding by wirelessly detecting presence of fluorescein-spiked blood in the stomach.","author":[{"dropping-particle":"","family":"Nemiroski","given":"Alex","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ryou","given":"Marvin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Thompson","given":"Christopher C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Westervelt","given":"Robert M.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Lab on a Chip","id":"ITEM-1","issue":"23","issued":{"date-parts":[["2015"]]},"page":"4479-4487","title":"Swallowable fluorometric capsule for wireless triage of gastrointestinal bleeding","type":"article-journal","volume":"15"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>83</sup>","plainTextFormattedCitation":"83","previouslyFormattedCitation":"<sup>83</sup>"},"properties":{"noteIndex":0},"schema":""}83 Single photon avalanche diode (SPAD) imaging arrays, capable of detecting a single photon of light, have been successfully used in AFI CE to improve the detection of endogenous fluorophores at low light intensity, removing the risk of phototoxic reactions and photobleaching [G] of the fluorophoresADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1529/biophysj.106.082388","ISBN":"0006-3495 (Print)\\r0006-3495 (Linking)","ISSN":"00063495","PMID":"16751234","abstract":"UVA light (320-400 nm) has been shown to produce deleterious biological effects in tissue due to the generation of singlet oxygen by substances like flavins or urocanic acid. Riboflavin, flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), β-nicotinamide adenine dinucleotide (NAD), and β-nicotinamide adenine dinucleotide phosphate (NADP), urocanic acid, or cholesterol in solution were excited at 355 nm. Singlet oxygen was directly detected by time-resolved measurement of its luminescence at 1270 nm. NAD, NADP, and cholesterol showed no luminescence signal possibly due to the very low absorption coefficient at 355 nm. Singlet oxygen luminescence of urocanic acid was clearly detected but the signal was too weak to quantify a quantum yield. The quantum yield of singlet oxygen was precisely determined for riboflavin (ΦΔ = 0.54 ± 0.07), FMN (ΦΔ = 0.51 ± 0.07), and FAD (ΦΔ = 0.07 ± 0.02). In aerated solution, riboflavin and FMN generate more singlet oxygen than exogenous photosensitizers such as Photofrin, which are applied in photodynamic therapy to kill cancer cells. With decreasing oxygen concentration, the quantum yield of singlet oxygen generation decreased, which must be considered when assessing the role of singlet oxygen at low oxygen concentrations (inside tissue). ? 2006 by the Biophysical Society.","author":[{"dropping-particle":"","family":"Baier","given":"Jürgen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Maisch","given":"Tim","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Maier","given":"Max","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Engel","given":"Eva","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Landthaler","given":"Michael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"B?umler","given":"Wolfgang","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Biophysical Journal","id":"ITEM-1","issue":"4","issued":{"date-parts":[["2006"]]},"page":"1452-1459","title":"Singlet oxygen generation by UVA light exposure of endogenous photosensitizers","type":"article-journal","volume":"91"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>84</sup>","plainTextFormattedCitation":"84","previouslyFormattedCitation":"<sup>84</sup>"},"properties":{"noteIndex":0},"schema":""}84. Furthermore, the use of complementary metal–oxide–semiconductor (CMOS) technology in the fabrication of both the SPAD imager and the associated electronic systems is vital to reduce the power required, allowing the capsule to be powered by silver-oxidewatch batteries for up to 15 hours, a lifetime similar to those of some clinical CE devices. SPAD imagers have been used in wireless CE prototypes developed by Al-Rawhani et al.ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1038/srep18591","ISSN":"2045-2322","PMID":"26678456","abstract":"Fluorescence Imaging (FI) is a powerful technique in biological science and clinical medicine. Current FI devices that are used either for in-vivo or in-vitro studies are expensive, bulky and consume substantial power, confining the technique to laboratories and hospital examination rooms. Here we present a miniaturised wireless fluorescence endoscope capsule with low power consumption that will pave the way for future FI systems and applications. With enhanced sensitivity compared to existing technology we have demonstrated that the capsule can be successfully used to image tissue autofluorescence and targeted fluorescence via fluorophore labelling of tissues. The capsule incorporates a state-of-the-art complementary metal oxide semiconductor single photon avalanche detector imaging array, miniaturised optical isolation, wireless technology and low power design. When in use the capsule consumes only 30.9 mW, and deploys very low-level 468 nm illumination. The device has the potential to replace highly power-hungry intrusive optical fibre based endoscopes and to extend the range of clinical examination below the duodenum. To demonstrate the performance of our capsule, we imaged fluorescence phantoms incorporating principal tissue fluorophores (flavins) and absorbers (haemoglobin). We also demonstrated the utility of marker identification by imaging a 20 μM fluorescein isothiocyanate (FITC) labelling solution on mammalian tissue.","author":[{"dropping-particle":"","family":"Al-Rawhani","given":"Mohammed A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Beeley","given":"James","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cumming","given":"David R. S.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Scientific Reports","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2015","11","18"]]},"page":"18591","publisher":"The Author(s)","title":"Wireless fluorescence capsule for endoscopy using single photon-based detection","type":"article-journal","volume":"5"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>81</sup>","plainTextFormattedCitation":"81","previouslyFormattedCitation":"<sup>81</sup>"},"properties":{"noteIndex":0},"schema":""}81. The highly sensitive SPAD pixels generate a pulse in response to the incidence of eacheach impinging photon, which enables individual photons due to autofluorescence to be counted. The latest version of the capsule contains a 32?x?32 pixel SPAD imager sufficient to demonstrate the diagnostic potential of this technologyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1038/srep18591","ISSN":"2045-2322","PMID":"26678456","abstract":"Fluorescence Imaging (FI) is a powerful technique in biological science and clinical medicine. Current FI devices that are used either for in-vivo or in-vitro studies are expensive, bulky and consume substantial power, confining the technique to laboratories and hospital examination rooms. Here we present a miniaturised wireless fluorescence endoscope capsule with low power consumption that will pave the way for future FI systems and applications. With enhanced sensitivity compared to existing technology we have demonstrated that the capsule can be successfully used to image tissue autofluorescence and targeted fluorescence via fluorophore labelling of tissues. The capsule incorporates a state-of-the-art complementary metal oxide semiconductor single photon avalanche detector imaging array, miniaturised optical isolation, wireless technology and low power design. When in use the capsule consumes only 30.9 mW, and deploys very low-level 468 nm illumination. The device has the potential to replace highly power-hungry intrusive optical fibre based endoscopes and to extend the range of clinical examination below the duodenum. To demonstrate the performance of our capsule, we imaged fluorescence phantoms incorporating principal tissue fluorophores (flavins) and absorbers (haemoglobin). We also demonstrated the utility of marker identification by imaging a 20 μM fluorescein isothiocyanate (FITC) labelling solution on mammalian tissue.","author":[{"dropping-particle":"","family":"Al-Rawhani","given":"Mohammed A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Beeley","given":"James","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cumming","given":"David R. S.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Scientific Reports","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2015","11","18"]]},"page":"18591","publisher":"The Author(s)","title":"Wireless fluorescence capsule for endoscopy using single photon-based detection","type":"article-journal","volume":"5"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>81</sup>","plainTextFormattedCitation":"81","previouslyFormattedCitation":"<sup>81</sup>"},"properties":{"noteIndex":0},"schema":""}81. However, an increase in resolution is required for routine clinical practice. Illumination in the prototype developed by Al-Rawhani et al. is provided by an inexpensive, compact LED at 468 nm with an emitted power of 78 μW being sufficient for this imager. Sensitivity is further improved by filtering out light other than that owing due to fluorescence emission. A common drawback of AFI techniques is that the signal from cancerous cells can be obscured by the autofluorescence of healthy cells. The capsule developed by Al-Rawhani et al. has yet to undergo in vivo trials, but benchmark tests have been conducted to assess its capability to detect autofluorescence from flavin adenine dinucleotide (FAD)FAD. an endogenous fluorophore associated with tumour growth, and the effect of haemoglobin on autofluorescence with a fluorescence emission peak of 520nm. The minimum amount of FAD detectable with this system is 12.5?μM, rising to 20 μM in a gut-mimicking imaging phantom. Similarly, this capsule can easily detect 20 μM of fluorescein isothiocyanate (FITC) The system can also detect a reduction in autofluorescence upon the introduction of haemoglobinADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1038/srep18591","ISSN":"2045-2322","PMID":"26678456","abstract":"Fluorescence Imaging (FI) is a powerful technique in biological science and clinical medicine. Current FI devices that are used either for in-vivo or in-vitro studies are expensive, bulky and consume substantial power, confining the technique to laboratories and hospital examination rooms. Here we present a miniaturised wireless fluorescence endoscope capsule with low power consumption that will pave the way for future FI systems and applications. With enhanced sensitivity compared to existing technology we have demonstrated that the capsule can be successfully used to image tissue autofluorescence and targeted fluorescence via fluorophore labelling of tissues. The capsule incorporates a state-of-the-art complementary metal oxide semiconductor single photon avalanche detector imaging array, miniaturised optical isolation, wireless technology and low power design. When in use the capsule consumes only 30.9 mW, and deploys very low-level 468 nm illumination. The device has the potential to replace highly power-hungry intrusive optical fibre based endoscopes and to extend the range of clinical examination below the duodenum. To demonstrate the performance of our capsule, we imaged fluorescence phantoms incorporating principal tissue fluorophores (flavins) and absorbers (haemoglobin). We also demonstrated the utility of marker identification by imaging a 20 μM fluorescein isothiocyanate (FITC) labelling solution on mammalian tissue.","author":[{"dropping-particle":"","family":"Al-Rawhani","given":"Mohammed A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Beeley","given":"James","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cumming","given":"David R. S.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Scientific Reports","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2015","11","18"]]},"page":"18591","publisher":"The Author(s)","title":"Wireless fluorescence capsule for endoscopy using single photon-based detection","type":"article-journal","volume":"5"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>81</sup>","plainTextFormattedCitation":"81","previouslyFormattedCitation":"<sup>81</sup>"},"properties":{"noteIndex":0},"schema":""}81. Capsules capable of sensing autofluorescence or fluorescence, as opposed to imaging capsules such as the Al-Rawhani capsule, were created for gastrointestinal diagnosis by Demosthenous et al.ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/TBCAS.2015.2449277","ISBN":"1932-4545 VO - 10","ISSN":"1932-4545","abstract":"Infrared fluorescence endoscopy (IRFE), in conjunction with an infrared fluorescent-labelling contrast agent, is a well known technique used for efficient early-stage cancer detection. In this paper we present a cost-effective ( $500) screening capsule prototype, which is able to detect infrared (IR) fluorescence emitted by indocyanine green (ICG) fluorophore dye. Rather than image, the capsule works as a high-sensitivity fluorometer that records fluorescence levels throughout the small intestine. The presented mixed-signal system has a small size, consumes very little power ( ≈ 6.3 mA) and does not require an external belt and hardware for data collection. By determining fluorescence levels in the intestine, rather than collecting images, we avoid the need for labour intensive video analysis. The whole system is contained within a compact ingestible capsule, that is sized so as to come into close contact with the intestine walls during peristalsis. Ex-vivo experiments, on ICG-impregnated swine intestine, have shown that the prototype system is able to detect low concentrations of ICG in the nanomolar and micromolar region, which is required to detect early cancer in the small intestine.","author":[{"dropping-particle":"","family":"Demosthenous","given":"Panayiota","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pitris","given":"Constantinos","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Georgiou","given":"Julius","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Transactions on Biomedical Circuits and Systems","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2016","4"]]},"page":"467-476","title":"Infrared Fluorescence-Based Cancer Screening Capsule for the Small Intestine","type":"article-journal","volume":"10"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>82</sup>","plainTextFormattedCitation":"82","previouslyFormattedCitation":"<sup>82</sup>"},"properties":{"noteIndex":0},"schema":""}82 and Nemiroski et al.ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1039/C5LC00770D","ISBN":"1473-0197","ISSN":"1473-0197","PMID":"26490455","abstract":"A swallowable, capsular fluorometer simplifies detection of upper gastrointestinal bleeding by wirelessly detecting presence of fluorescein-spiked blood in the stomach.","author":[{"dropping-particle":"","family":"Nemiroski","given":"Alex","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ryou","given":"Marvin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Thompson","given":"Christopher C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Westervelt","given":"Robert M.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Lab on a Chip","id":"ITEM-1","issue":"23","issued":{"date-parts":[["2015"]]},"page":"4479-4487","title":"Swallowable fluorometric capsule for wireless triage of gastrointestinal bleeding","type":"article-journal","volume":"15"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>83</sup>","plainTextFormattedCitation":"83","previouslyFormattedCitation":"<sup>83</sup>"},"properties":{"noteIndex":0},"schema":""}83 . These devices detect light with photo-diodes rather than SPAD imagers. Demosthenous et al.ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/TBCAS.2015.2449277","ISBN":"1932-4545 VO - 10","ISSN":"1932-4545","abstract":"Infrared fluorescence endoscopy (IRFE), in conjunction with an infrared fluorescent-labelling contrast agent, is a well known technique used for efficient early-stage cancer detection. In this paper we present a cost-effective ( $500) screening capsule prototype, which is able to detect infrared (IR) fluorescence emitted by indocyanine green (ICG) fluorophore dye. Rather than image, the capsule works as a high-sensitivity fluorometer that records fluorescence levels throughout the small intestine. The presented mixed-signal system has a small size, consumes very little power ( ≈ 6.3 mA) and does not require an external belt and hardware for data collection. By determining fluorescence levels in the intestine, rather than collecting images, we avoid the need for labour intensive video analysis. The whole system is contained within a compact ingestible capsule, that is sized so as to come into close contact with the intestine walls during peristalsis. Ex-vivo experiments, on ICG-impregnated swine intestine, have shown that the prototype system is able to detect low concentrations of ICG in the nanomolar and micromolar region, which is required to detect early cancer in the small intestine.","author":[{"dropping-particle":"","family":"Demosthenous","given":"Panayiota","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pitris","given":"Constantinos","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Georgiou","given":"Julius","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Transactions on Biomedical Circuits and Systems","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2016","4"]]},"page":"467-476","title":"Infrared Fluorescence-Based Cancer Screening Capsule for the Small Intestine","type":"article-journal","volume":"10"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>82</sup>","plainTextFormattedCitation":"82","previouslyFormattedCitation":"<sup>82</sup>"},"properties":{"noteIndex":0},"schema":""}82 used their CE device to measure the changing level of fluorescent light generated by low concentrations of an exogenous infrared fluorescent marker (indocyanine green, (ICG)) to screen for cancer in ex vivo porcine small intestine. ICG was chosen as the fluorophore, as it is used to tag cancerous cells with a fluorescent signal in other regions of the gastrointestinal tractADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/S1590-8658(03)00005-7","ISBN":"8188633712","ISSN":"15908658","PMID":"12747626","abstract":"Background and aims. An indocyanine green derivative (ICG-sulfo-OSu) and agents for reinforcement of infrared fluorescence, which can be used as an infrared fluorescent labeling substance suitable for detection of microlesions by an IR fluorescence endoscope, have been developed. The study aims were to confirm the ability of a reinforcement agent, as well as imaging processing, to intensify fluorescence from the labeled antibody on immunohistochemical staining. Subjects and methods. ICG-sulfo-OSu-labeled MUC1 antibody and an IR fluorescence imaging system were employed in the present study. Paraffin sections of gastric cancer were stained with anti-MUC1 antibody by the avidin-biotinylated peroxidase complex method. Among the positive specimens, three cases were used for IR imaging analysis. Octylglucoside was used as a reinforcement agent. Results. The incubation of paraffin sections with ICG-sulfo-OSu-labeled MUC1 antibody resulted in positive staining of the tumor sites by an IR fluorescence imaging system, and the intensity of fluorescence was increased depending on the concentration of octylglucoside and grade of imaging processing. Conclusion. A reinforcement agent, and image processing, intensify a labeled antibody excitable by infrared fluorescence in tumor sections and can generate a strong enough fluorescent signal to detect small cancers when examined with an infrared fluorescence endoscope. ? 2003 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Science Ireland Ltd. All rights reserved.","author":[{"dropping-particle":"","family":"Inayama","given":"K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ito","given":"S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Muguruma","given":"N.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kusaka","given":"Y.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bando","given":"T.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tadatsu","given":"Y.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tadatsu","given":"M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ii","given":"K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shibamura","given":"S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Takesako","given":"K.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Digestive and Liver Disease","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2003"]]},"page":"88-93","title":"Basic study of an agent for reinforcement of near-infrared fluorescence on tumor tissue","type":"article-journal","volume":"35"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1109/APBP.2004.1412359","ISBN":"1343-1420 (Print)\\r1343-1420 (Linking)","ISSN":"1343-1420","PMID":"16537990","abstract":"Since there is no infrared fluorescence materials in the living body, infrared fluorescence labeling materials are very useful for making a diagnosis of a micro cancer. We have developed an infrared fluorescence endoscope (IRFE) and indocyanin green (ICG)-derivative as infrared fluorescence labeling materials to evaluate gastrointestinal neoplastic lesions. The study aims were to apply an IRFE and to demonstrate its usefulness in detecting cancerous tissue using an antibody coupled with ICG-derivative. IRFE consisted of an infrared endoscope equipped with excitation (710-790 nm) and barrier (810-920 nm) filters and an intensified CCD camera. We have developed ICG N-hydroxy sulfo succinimide ester (ICG-sulfo-OSu) and 3-ICG-acyl-1, 3-thiazolidine-2-thione (ICG-ATT) as an infrared fluorescent-labeling reagent. ICG-derivative-labeled mouse anti-human carcinoembryonic antigen (CEA) antibody and MUC1 antibody were employed in this study. Moreover, we examined the ability of a reinforcement agent, octylglucoside, to intensity fluorescence from the labeled antibody. Biopsy specimens of gastric cancer were stained with anti-CEA antibody by the avidin-biotinylated peroxidase complex method. Among the positive specimens, freshly resected stomach from three cases were used for the infrared (IR) imaging analysis. The incubation of freshly resected stomach specimens with ICG-anti-CEA antibody-complex resulted in positive staining of the tumor sites by IRFE, and the IR fluorescent images correlated well with the tumor sites. The immunohistochemical studies suggested that the intensity of IR fluorescence of ICG-ATT-MUC1 was stronger than that of ICG-sulfo-OSu. In tumor sections, the reinforcement agent intensified fluorescence, ever at low antibody concentrations. Therefore, we conclude that an anti-CEA (and/or MUC1) antibody with affinity for cancerous lesions and labeled with ICG-derivative can be imaged with this IRFE. Specific antibodies tagged with ICG-derivative with the reinforcement agent can label cancer cells and generate a strong enough fluorescent signal to detect small cancers when examined with an IR fluorescence endoscope.","author":[{"dropping-particle":"","family":"Ito","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Muguruma","given":"N","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kimura","given":"T","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yano","given":"H","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Imoto","given":"Y","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Okamoto","given":"K","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kaji","given":"M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sano","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nagao","given":"Y","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"J Med Invest","id":"ITEM-2","issue":"1-2","issued":{"date-parts":[["2006"]]},"page":"1-8","title":"Principle and clinical usefulness of the infrared fluorescence endoscopy","type":"article-journal","volume":"53"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>85,86</sup>","plainTextFormattedCitation":"85,86","previouslyFormattedCitation":"<sup>85,86</sup>"},"properties":{"noteIndex":0},"schema":""}85,86 and the absorption spectrum can be modified through changes in concentration. This latteris property enables the excitation wavelength to be altered for optimal detection of specific pathologies or improved tissue penetration; for instance, at low concentrations, such as those expected in small cancers, the optimum excitation wavelength is 780?nm. Increasing the concentration causes a second absorption wavelength to appear at 708?nmADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/TBCAS.2015.2449277","ISBN":"1932-4545 VO - 10","ISSN":"1932-4545","abstract":"Infrared fluorescence endoscopy (IRFE), in conjunction with an infrared fluorescent-labelling contrast agent, is a well known technique used for efficient early-stage cancer detection. In this paper we present a cost-effective ( $500) screening capsule prototype, which is able to detect infrared (IR) fluorescence emitted by indocyanine green (ICG) fluorophore dye. Rather than image, the capsule works as a high-sensitivity fluorometer that records fluorescence levels throughout the small intestine. The presented mixed-signal system has a small size, consumes very little power ( ≈ 6.3 mA) and does not require an external belt and hardware for data collection. By determining fluorescence levels in the intestine, rather than collecting images, we avoid the need for labour intensive video analysis. The whole system is contained within a compact ingestible capsule, that is sized so as to come into close contact with the intestine walls during peristalsis. Ex-vivo experiments, on ICG-impregnated swine intestine, have shown that the prototype system is able to detect low concentrations of ICG in the nanomolar and micromolar region, which is required to detect early cancer in the small intestine.","author":[{"dropping-particle":"","family":"Demosthenous","given":"Panayiota","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pitris","given":"Constantinos","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Georgiou","given":"Julius","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Transactions on Biomedical Circuits and Systems","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2016","4"]]},"page":"467-476","title":"Infrared Fluorescence-Based Cancer Screening Capsule for the Small Intestine","type":"article-journal","volume":"10"},"uris":[""]},{"id":"ITEM-2","itemData":{"ISBN":"0001-527X (Print)\\r0001-527X (Linking)","ISSN":"0001527X","PMID":"12362980","abstract":"Spectroscopic, photochemical and biological properties of indocyanine green (ICG) are presented. Light over 800 nm is effectively absorbed by ICG. This property as well as photochemical behaviour of ICG make it a very suitable dye for photodynamic treatment of melanoma cells. Cytotoxicity of ICG itself and the effect of photodynamic therapy (PDT) were evaluated by following the growth of human (SKMEL 188) and mouse (S91) melanoma cells. The surviving fraction of the cells irradiated (lambda(ex) = 830 nm) vs non-irradiated, treated with the same dose of ICG, is significantly decreased (5- to 10-fold). These results show that ICG is a very promising dye for photodynamic therapy of melanomas.","author":[{"dropping-particle":"","family":"Urbanska","given":"Krystyna","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Romanowska-Dixon","given":"Bozena","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Matuszak","given":"Zenon","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Oszajca","given":"Janusz","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nowak-Sliwinska","given":"Patrycja","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stochel","given":"Grazyna","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Acta Biochimica Polonica","id":"ITEM-2","issue":"2","issued":{"date-parts":[["2002"]]},"page":"387-391","title":"Indocyanine green as a prospective sensitizer for photodynamic therapy of melanomas","type":"article-journal","volume":"49"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>82,87</sup>","plainTextFormattedCitation":"82,87","previouslyFormattedCitation":"<sup>82,87</sup>"},"properties":{"noteIndex":0},"schema":""}82,87. Demosthenous and colleagues designed their autonomous system for use with 780nm wavelength excitation, as the deeper tissue penetration depth at this wavelength is more suitable for detecting small cancersADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.2169/internalmedicine.38.537","ISBN":"0918-2918; 0918-2918","ISSN":"0918-2918","abstract":"OBJECT: An indocyanine green derivative (ICG-sulfo-OSu) was used as the labeling substance for monoclonal antibody, and a fluorescence imaging system appropriate for ICG-sulfo-OSu excitable by infrared rays (IR) was developed. The goal of this study was to demonstrate antibody labeling at the tissue level using this new imaging system. MATERIALS AND METHODS: ICG-sulfo-OSu labeled mouse anti-human carcinoembryonic antigen (CEA) monoclonal antibody, a newly developed imaging system, and an infrared ray microscope were employed in this experiment. Paraffin sections of human colon cancer previously proven to have cross-reactivity to anti-CEA antibody were examined. RESULTS: Positive staining was seen as a brownish discoloration of oxidized 3,3'-diaminobenzidine tetrahydrochloride (DAB) in sections that reacted with ICG-sulfo-OSu-labeled anti-CEA antibody, and the fluorescence was well-matched with the oxidized DAB-positive sites. CONCLUSION: Specific antibodies labeled with ICG-sulfo-OSu have significant affinity to cancer cells and seem to reflect sufficient amounts of fluorescence by IR to be useful in a system for the endoscopic detection of micro cancers using the immunohistochemical staining method.","author":[{"dropping-particle":"","family":"MUGURUMA","given":"Naoki","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"ITO","given":"Susumu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"BANDO","given":"Terumi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"TAOKA","given":"Satoko","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"KUSAKA","given":"Yoshihiro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"HAYASHI","given":"Shigehito","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"ICHIKAWA","given":"Soichi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"MATSUNAGA","given":"Yuko","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"TADA","given":"Yoshie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"OKAMURA","given":"Seisuke","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"II","given":"Kunio","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"IMAIZUMI","given":"Katsuichi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"NAKAMURA","given":"Kazunari","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"TAKESAKO","given":"Kazuhiro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"SHIBAMURA","given":"Seiichi","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Internal Medicine","id":"ITEM-1","issue":"7","issued":{"date-parts":[["1999"]]},"page":"537-542","title":"Labeled Carcinoembryonic Antigen Antibodies Excitable by Infrared Rays. A Novel Diagnostic Method for Micro Cancers in the Digestive Tract.","type":"article-journal","volume":"38"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1016/S0968-0896(03)00239-6","ISBN":"8188633712","ISSN":"09680896","PMID":"12837539","abstract":"Purpose: We have developed infrared fluorescent labeling agents and infrared-ray fluorescence endoscopes to establish a novel diagnostic technique. Since the fluorescence intensity of the initial labeled antibody (ICG-sulfo-OSu-labeled antibody) was not sufficient for practical use, we synthesized indocyanine green acylthiazolidinethione (ICG-ATT), which was expected to label various target molecules having amino groups efficiently. Materials and Methods: To confirm imaging of infrared fluorescence intensity of ICG-ATT- and ICG-sulfo-OSu-labeled anti-MUC1 antibodies, cotton thread was soaked in various concentrations of the antibody solution in 0.1 M PBS, and observed under the epi-illumination infrared fluorescence microscope. Localization and the intensity of infrared fluorescence and DAB coloring was compared in paraffin sections of human gastric mucosa. Results: In the study of cotton threads, both labeled antibodies showed relatively clear infrared fluorescence, and significant difference was not observed between the two antibodies. ICG-ATT-labeled anti-MUC1 antibody produced stronger staining than that by ICG-sulfo-OSu-labeled antibody. Localization pattern of infrared fluorescent staining was in good agreement with that by the conventional method with oxidized DAB staining. Conclusion: ICG-ATT is useful as a fluorescent-labeling agent for diagnosis of microcancers by infrared fluorescence endoscopes. ? 2003 Elsevier Science Ltd. All rights reserved.","author":[{"dropping-particle":"","family":"Tadatsu","given":"Masaya","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ito","given":"Susumu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Muguruma","given":"Naoki","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kusaka","given":"Yoshihiro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Inayama","given":"Kumi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bando","given":"Terumi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tadatsu","given":"Yoko","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Okamoto","given":"Koichi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kunio","given":"","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nagao","given":"Yoshimitsu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sano","given":"Shigeki","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Taue","given":"Hiromi","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Bioorganic & Medicinal Chemistry","id":"ITEM-2","issue":"15","issued":{"date-parts":[["2003","7"]]},"page":"3289-3294","title":"A new infrared fluorescent-Labeling agent and labeled antibody for diagnosing microcancers","type":"article-journal","volume":"11"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>88,89</sup>","plainTextFormattedCitation":"88,89","previouslyFormattedCitation":"<sup>88,89</sup>"},"properties":{"noteIndex":0},"schema":""}88,89 and the rate of false positives arising from endogenous fluorophores within surrounding tissue that emit light in the ultravioletUV and other parts of the visible spectrum is reducedADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/j.1751-1097.1998.tb02521.x","ISSN":"00318655","PMID":"9825692","author":[{"dropping-particle":"","family":"Wagnières","given":"Georges A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Star","given":"Willem M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wilson","given":"Brian C.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Photochemistry and Photobiology","id":"ITEM-1","issue":"5","issued":{"date-parts":[["1998"]]},"page":"603-632","title":"In Vivo Fluorescence Spectroscopy and Imaging for Oncological Applications","type":"article","volume":"68"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>90</sup>","plainTextFormattedCitation":"90","previouslyFormattedCitation":"<sup>90</sup>"},"properties":{"noteIndex":0},"schema":""}90. The functionality of this capsule has yet to be determined in an in vivo environment. However, ex vivo experiments using porcine intestinal tissue have demonstrated the capability to detect nanomolar to micromolar concentrations of ICG, which are comparable to those that would be expected from tagged small cancersADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/TBCAS.2015.2449277","ISBN":"1932-4545 VO - 10","ISSN":"1932-4545","abstract":"Infrared fluorescence endoscopy (IRFE), in conjunction with an infrared fluorescent-labelling contrast agent, is a well known technique used for efficient early-stage cancer detection. In this paper we present a cost-effective ( $500) screening capsule prototype, which is able to detect infrared (IR) fluorescence emitted by indocyanine green (ICG) fluorophore dye. Rather than image, the capsule works as a high-sensitivity fluorometer that records fluorescence levels throughout the small intestine. The presented mixed-signal system has a small size, consumes very little power ( ≈ 6.3 mA) and does not require an external belt and hardware for data collection. By determining fluorescence levels in the intestine, rather than collecting images, we avoid the need for labour intensive video analysis. The whole system is contained within a compact ingestible capsule, that is sized so as to come into close contact with the intestine walls during peristalsis. Ex-vivo experiments, on ICG-impregnated swine intestine, have shown that the prototype system is able to detect low concentrations of ICG in the nanomolar and micromolar region, which is required to detect early cancer in the small intestine.","author":[{"dropping-particle":"","family":"Demosthenous","given":"Panayiota","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pitris","given":"Constantinos","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Georgiou","given":"Julius","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Transactions on Biomedical Circuits and Systems","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2016","4"]]},"page":"467-476","title":"Infrared Fluorescence-Based Cancer Screening Capsule for the Small Intestine","type":"article-journal","volume":"10"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>82</sup>","plainTextFormattedCitation":"82","previouslyFormattedCitation":"<sup>82</sup>"},"properties":{"noteIndex":0},"schema":""}82. Nemiroski and colleagues designed their wireless capsule to detect gastrointestinal bleeding (GIB)ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1039/C5LC00770D","ISBN":"1473-0197","ISSN":"1473-0197","PMID":"26490455","abstract":"A swallowable, capsular fluorometer simplifies detection of upper gastrointestinal bleeding by wirelessly detecting presence of fluorescein-spiked blood in the stomach.","author":[{"dropping-particle":"","family":"Nemiroski","given":"Alex","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ryou","given":"Marvin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Thompson","given":"Christopher C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Westervelt","given":"Robert M.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Lab on a Chip","id":"ITEM-1","issue":"23","issued":{"date-parts":[["2015"]]},"page":"4479-4487","title":"Swallowable fluorometric capsule for wireless triage of gastrointestinal bleeding","type":"article-journal","volume":"15"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>83</sup>","plainTextFormattedCitation":"83","previouslyFormattedCitation":"<sup>83</sup>"},"properties":{"noteIndex":0},"schema":""}83. Although WLI CE can be used to identify blood in the stomach, it cannot easily differentiate between past and active GIB in the stomach. Such differentiation is achieved in the Nemiroski capsule through the intravenous injection of fluorescein, a fluorescent contrast agent. Fluorescein is chosen as a proxy for active GIB as it is FDA compliant, has a quantum yield [G] of ~90% and the optical spectrum (absorption peak at 494 nm, emission peak at 512 nm) does not overlap with the autofluorescent spectrum of gastric juices (absorption peak at 288 nm; emission peak at 350 nm). The distance between the two pairs of emission and absorption peaks enables fluorescein to act as a biomarker for the detection of blood in the stomach. The capsule uses a miniaturized fluorometer consisting of a LED, optics and photodiode for detection of the emitted fluorescent signal. The LED peak wavelength is 465?nm, and the use of filters limits the light from sources other than the fluorescein that is detected by the photodiode. Benchtop tests have demonstrated that the system can detect concentrations of fluorescein as low as 20?nM. However, the performance of the system varies with the pH of the stomach as the spectral properties and quantum yield of fluorescein shift with pH, which can be problematic after the patient ingests water. In vivo trials have yet to be carried out with this capsule. [H3]Optical coherence tomographyOCT is a volumetric imaging [G] technology capable of micrometreer scale resolution that operates by scanning an optical beam across the sample and measuring the time delay and intensity of backscattered or back-reflected lightADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.3390/diagnostics4020057","ISSN":"2075-4418","author":[{"dropping-particle":"","family":"Tsai","given":"Tsung-Han","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fujimoto","given":"James","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mashimo","given":"Hiroshi","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Diagnostics","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2014","5","5"]]},"page":"57-93","title":"Endoscopic Optical Coherence Tomography for Clinical Gastroenterology","type":"article-journal","volume":"4"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>91</sup>","plainTextFormattedCitation":"91","previouslyFormattedCitation":"<sup>91</sup>"},"properties":{"noteIndex":0},"schema":""}91. Improvements in the speed and sensitivity of OCT technologyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.3390/diagnostics4020057","ISSN":"2075-4418","author":[{"dropping-particle":"","family":"Tsai","given":"Tsung-Han","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fujimoto","given":"James","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mashimo","given":"Hiroshi","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Diagnostics","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2014","5","5"]]},"page":"57-93","title":"Endoscopic Optical Coherence Tomography for Clinical Gastroenterology","type":"article-journal","volume":"4"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>91</sup>","plainTextFormattedCitation":"91","previouslyFormattedCitation":"<sup>91</sup>"},"properties":{"noteIndex":0},"schema":""}91, coupled with an image resolution comparable with that achieved with conventional histological analysis of excised biopsy (10 ?m axial and 30 ?m lateral resolution), make this an attractive technology for real-time, in vivo virtual biopsy applications. OCT was successfully applied to in vivo studies of the duodenum in 2005ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/S0016-5107(05)00323-8","ISSN":"00165107","author":[{"dropping-particle":"","family":"Yang","given":"Victor X.D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tang","given":"Shou-jiang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gordon","given":"Maggie L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Qi","given":"Bing","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gardiner","given":"Geoffrey","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cirocco","given":"Maria","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kortan","given":"Paul","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Haber","given":"Gregory B.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kandel","given":"Gabor","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Vitkin","given":"I. Alex","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wilson","given":"Brian C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Marcon","given":"Norman E.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastrointestinal Endoscopy","id":"ITEM-1","issue":"7","issued":{"date-parts":[["2005","6"]]},"page":"879-890","title":"Endoscopic Doppler optical coherence tomography in the human GI tract: initial experience","type":"article-journal","volume":"61"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1364/BOE.8.002405","ISSN":"2156-7085","PMID":"28663882","abstract":"In this paper, we review the current state of technology development and clinical applications of endoscopic optical coherence tomography (OCT). Key design and engineering considerations are discussed for most OCT endoscopes, including side-viewing and forward-viewing probes, along with different scanning mechanisms (proximal-scanning versus distal-scanning). Multi-modal endoscopes that integrate OCT with other imaging modalities are also discussed. The review of clinical applications of endoscopic OCT focuses heavily on diagnosis of diseases and guidance of interventions. Representative applications in several organ systems are presented, such as in the cardiovascular, digestive, respiratory, and reproductive systems. A brief outlook of the field of endoscopic OCT is also discussed.","author":[{"dropping-particle":"","family":"Gora","given":"Michalina J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Suter","given":"Melissa J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tearney","given":"Guillermo J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Li","given":"Xingde","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Biomedical Optics Express","id":"ITEM-2","issue":"5","issued":{"date-parts":[["2017"]]},"page":"2405","title":"Endoscopic optical coherence tomography: technologies and clinical applications [Invited]","type":"article-journal","volume":"8"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>92,93</sup>","plainTextFormattedCitation":"92,93","previouslyFormattedCitation":"<sup>92,93</sup>"},"properties":{"noteIndex":0},"schema":""}92,93. An image was reconstructed from the measured light that demonstrated that the intestinal villi could be observedADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1364/BOE.8.002405","ISSN":"2156-7085","PMID":"28663882","abstract":"In this paper, we review the current state of technology development and clinical applications of endoscopic optical coherence tomography (OCT). Key design and engineering considerations are discussed for most OCT endoscopes, including side-viewing and forward-viewing probes, along with different scanning mechanisms (proximal-scanning versus distal-scanning). Multi-modal endoscopes that integrate OCT with other imaging modalities are also discussed. The review of clinical applications of endoscopic OCT focuses heavily on diagnosis of diseases and guidance of interventions. Representative applications in several organ systems are presented, such as in the cardiovascular, digestive, respiratory, and reproductive systems. A brief outlook of the field of endoscopic OCT is also discussed.","author":[{"dropping-particle":"","family":"Gora","given":"Michalina J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Suter","given":"Melissa J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tearney","given":"Guillermo J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Li","given":"Xingde","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Biomedical Optics Express","id":"ITEM-1","issue":"5","issued":{"date-parts":[["2017"]]},"page":"2405","title":"Endoscopic optical coherence tomography: technologies and clinical applications [Invited]","type":"article-journal","volume":"8"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>93</sup>","plainTextFormattedCitation":"93","previouslyFormattedCitation":"<sup>93</sup>"},"properties":{"noteIndex":0},"schema":""}93. Studies in 2007 showed that OCT combined with EGD could be successfully used to detect celiaccoeliac disease by analysis of the villous morphology from the OCT images, with a sensitivity of 82% and specificity of 100% achieved in a study of 132 paediatric patientsADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.dld.2009.02.002","ISSN":"15908658","author":[{"dropping-particle":"","family":"Masci","given":"E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mangiavillano","given":"B.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Barera","given":"G.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Parma","given":"B.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Albarello","given":"L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mariani","given":"A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Doglioni","given":"C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Testoni","given":"P.A.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Digestive and Liver Disease","id":"ITEM-1","issue":"9","issued":{"date-parts":[["2009","9"]]},"page":"639-643","title":"Optical coherence tomography in pediatric patients: A feasible technique for diagnosing celiac disease in children with villous atrophy","type":"article-journal","volume":"41"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>94</sup>","plainTextFormattedCitation":"94","previouslyFormattedCitation":"<sup>94</sup>"},"properties":{"noteIndex":0},"schema":""}94. The potential for OCT in the diagnosis of IBD has been demonstrated by several studies, with the first reporting that transmural inflammation detected by OCT could distinguish Crohn’s disease from ulcerative colitis with a sensitivity?of?90.0% and specificity?of?83.3%ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"ISSN":"1542-3565","PMID":"15625653","abstract":"BACKGROUND & AIMS Transmural inflammation, a distinguishing feature of Crohn's disease (CD), cannot be assessed by conventional colonoscopy with mucosal biopsy. Our previous ex vivo study of histology-correlated optical coherence tomography (OCT) imaging on colectomy specimens of CD and ulcerative colitis (UC) showed that disruption of the layered structure of colon wall on OCT is an accurate marker for transmural inflammation of CD. We performed an in vivo colonoscopic OCT in patients with a clinical diagnosis of CD or UC using the previously established, histology-correlated OCT imaging criterion. METHODS OCT was performed in 40 patients with CD (309 images) and 30 patients with UC (292 images). Corresponding endoscopic features of mucosal inflammation were documented. Two gastroenterologists blinded to endoscopic and clinical data scored the OCT images independently to assess the feature of disrupted layered structure. RESULTS Thirty-six CD patients (90.0%) had disrupted layered structure, whereas 5 UC patients (16.7%) had disrupted layered structure (P < .001). Using the clinical diagnosis of CD or UC as the gold standard, the disrupted layered structure on OCT indicative of transmural inflammation had a diagnostic sensitivity and specificity of 90.0% (95% CI: 78.0%, 96.5%) and 83.3% (95% CI: 67.3%, 93.3%) for CD, respectively. The kappa coefficient in the interpretation of OCT images was 0.80 (95% CI: 0.75, 0.86, P < .001). CONCLUSIONS In vivo colonoscopic OCT is feasible and accurate to detect disrupted layered structure of the colon wall indicative of transmural inflammation, providing a valuable tool to distinguish CD from UC.","author":[{"dropping-particle":"","family":"Shen","given":"Bo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zuccaro","given":"Gregory","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gramlich","given":"Terry L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gladkova","given":"Natalie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Trolli","given":"Patricia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kareta","given":"Margaret","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Delaney","given":"Conor P","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Connor","given":"Jason T","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lashner","given":"Bret A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bevins","given":"Charles L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Feldchtein","given":"Felix","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Remzi","given":"Feza H","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bambrick","given":"Marlene L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fazio","given":"Victor W","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association","id":"ITEM-1","issue":"12","issued":{"date-parts":[["2004","12"]]},"page":"1080-7","title":"In vivo colonoscopic optical coherence tomography for transmural inflammation in inflammatory bowel disease.","type":"article-journal","volume":"2"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>95</sup>","plainTextFormattedCitation":"95","previouslyFormattedCitation":"<sup>95</sup>"},"properties":{"noteIndex":0},"schema":""}95. A subsequent study also found similar discrimination between ulcerative colitis and Crohn’s disease ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1007/s10350-008-9304-6","ISSN":"0012-3706","author":[{"dropping-particle":"","family":"Consolo","given":"P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Strangio","given":"G.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Luigiano","given":"C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Giacobbe","given":"G.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pallio","given":"S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Familiari","given":"L.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Diseases of the Colon & Rectum","id":"ITEM-1","issue":"9","issued":{"date-parts":[["2008","9"]]},"page":"1374-1380","title":"Optical Coherence Tomography in Inflammatory Bowel Disease: Prospective Evaluation of 35 Patients","type":"article-journal","volume":"51"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>96</sup>","plainTextFormattedCitation":"96","previouslyFormattedCitation":"<sup>96</sup>"},"properties":{"noteIndex":0},"schema":""}96. Both of these studies involved 2D images; although a subsequent study generated 3D reconstructions of the colon, rectum and anal verge in patients with ulcerative colitis that visualized the presence of large subsurface voids, ulcerations and the absence of a regular crypt patternADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1088/0031-9155/55/20/011.DigiWarp","ISBN":"1545968309332","ISSN":"1094-4087","PMID":"19158891","abstract":"Three-dimensional (3D) endomicroscopy imaging of the human gastrointestinal tract is demonstrated in vivo using a swept source optical coherence tomography (OCT) system. 3D datasets of normal and pathologic regions of the colon, rectum, and anal verge were obtained from seven volunteers undergoing diagnostic or therapeutic colonoscopy. 3D-OCT enables high resolution endomicroscopy examination through visualization of tissue architectural morphology using virtual cross-sectional images with arbitrary orientations as well as en face projection images. Axial image resolutions of 6 mum in tissue are obtained over a approximately 180 mm2 field with an imaging range of 1.6 mm. A Fourier domain mode locked (FDML) laser providing a tuning range of 180 nm at a sweep rate of 62 kHz is used as the system light source. This clinical pilot study demonstrates the potential of 3D-OCT for distinguishing normal from pathologic colorectal tissue, assessing endoscopic therapies and healing progression.","author":[{"dropping-particle":"","family":"Adler","given":"Desmond C","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zhou","given":"Chao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tsai","given":"Tsung-Han","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schmitt","given":"Joe","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Huang","given":"Qin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mashimo","given":"Hiroshi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fujimoto","given":"James G","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Optics express","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2009","1","19"]]},"page":"784-96","title":"Three-dimensional endomicroscopy of the human colon using optical coherence tomography.","type":"article-journal","volume":"17"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>97</sup>","plainTextFormattedCitation":"97","previouslyFormattedCitation":"<sup>97</sup>"},"properties":{"noteIndex":0},"schema":""}97.Attempts to integrate OCT into CE have so far been limited to two, independently produced, tethered capsule endoscopes for diagnosing esophagealoesophageal pathologyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1038/nm.3052","ISBN":"1546-170X (Electronic)\\n1078-8956 (Linking)","ISSN":"10788956","PMID":"23314056","abstract":"Here we introduce tethered capsule endomicroscopy, which involves swallowing an optomechanically engineered pill that captures cross-sectional microscopic images of the gut wall at 30 μm (lateral) × 7 μm (axial) resolution as it travels through the digestive tract. Results in human subjects show that this technique rapidly provides three-dimensional, microstructural images of the upper gastrointestinal tract in a simple and painless procedure, opening up new opportunities for screening for internal diseases.","author":[{"dropping-particle":"","family":"Gora","given":"Michalina J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sauk","given":"Jenny S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Carruth","given":"Robert W.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gallagher","given":"Kevin A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Suter","given":"Melissa J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nishioka","given":"Norman S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kava","given":"Lauren E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rosenberg","given":"Mireille","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bouma","given":"Brett E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tearney","given":"Guillermo J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Nature Medicine","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2013","2","13"]]},"page":"238-240","title":"Tethered capsule endomicroscopy enables less invasive imaging of gastrointestinal tract microstructure","type":"article-journal","volume":"19"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1364/BOE.6.001146","ISBN":"2156-7085","ISSN":"2156-7085","PMID":"25909001","abstract":"Depth resolved and en face OCT visualization in vivo may have important clinical applications in endoscopy. We demonstrate a high speed, two-dimensional (2D) distal scanning capsule with a micromotor for fast rotary scanning and a pneumatic actuator for precision longitudinal scanning. Longitudinal position measurement and image registration were performed by optical tracking of the pneumatic scanner. The 2D scanning device enables high resolution imaging over a small field of view and is suitable for OCT as well as other scanning microscopies. Large field of view imaging for screening or surveillance applications can also be achieved by proximally pulling back or advancing the capsule while scanning the distal high-speed micromotor. Circumferential en face OCT was demonstrated in living swine at 250 Hz frame rate and 1 MHz A-scan rate using a MEMS tunable VCSEL light source at 1300 nm. Cross-sectional and en face OCT views of the upper and lower gastrointestinal tract were generated with precision distal pneumatic longitudinal actuation as well as proximal manual longitudinal actuation. These devices could enable clinical studies either as an adjunct to endoscopy, attached to an endoscope, or as a swallowed tethered capsule for non-endoscopic imaging without sedation. The combination of ultrahigh speed imaging and distal scanning capsule technology could enable both screening and surveillance applications.","author":[{"dropping-particle":"","family":"Liang","given":"Kaicheng","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Traverso","given":"Giovanni","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lee","given":"Hsiang-Chieh","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ahsen","given":"Osman Oguz","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wang","given":"Zhao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Potsaid","given":"Benjamin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Giacomelli","given":"Michael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jayaraman","given":"Vijaysekhar","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Barman","given":"Ross","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cable","given":"Alex","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mashimo","given":"Hiroshi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Langer","given":"Robert","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fujimoto","given":"James G.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Biomedical Optics Express","id":"ITEM-2","issue":"4","issued":{"date-parts":[["2015","4","1"]]},"page":"1146","title":"Ultrahigh speed en face OCT capsule for endoscopic imaging","type":"article-journal","volume":"6"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>98,99</sup>","plainTextFormattedCitation":"98,99","previouslyFormattedCitation":"<sup>98,99</sup>"},"properties":{"noteIndex":0},"schema":""}98,99. In both referenced cases, the tether encases an optical fibreer used to transmit light from an external light source to internal optics that are mechanically scanned to produce the image. The tethered capsule developed by Gora et al.ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1038/nm.3052","ISBN":"1546-170X (Electronic)\\n1078-8956 (Linking)","ISSN":"10788956","PMID":"23314056","abstract":"Here we introduce tethered capsule endomicroscopy, which involves swallowing an optomechanically engineered pill that captures cross-sectional microscopic images of the gut wall at 30 μm (lateral) × 7 μm (axial) resolution as it travels through the digestive tract. Results in human subjects show that this technique rapidly provides three-dimensional, microstructural images of the upper gastrointestinal tract in a simple and painless procedure, opening up new opportunities for screening for internal diseases.","author":[{"dropping-particle":"","family":"Gora","given":"Michalina J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sauk","given":"Jenny S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Carruth","given":"Robert W.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gallagher","given":"Kevin A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Suter","given":"Melissa J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nishioka","given":"Norman S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kava","given":"Lauren E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rosenberg","given":"Mireille","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bouma","given":"Brett E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tearney","given":"Guillermo J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Nature Medicine","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2013","2","13"]]},"page":"238-240","title":"Tethered capsule endomicroscopy enables less invasive imaging of gastrointestinal tract microstructure","type":"article-journal","volume":"19"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>98</sup>","plainTextFormattedCitation":"98","previouslyFormattedCitation":"<sup>98</sup>"},"properties":{"noteIndex":0},"schema":""}98 was 12.8?mm in diameter and 24.8 mm long with side-viewing OCT capable of generating radial images at 20 frames per second with 30?μm lateral and 7?μm axial resolution in humans. This capsule rotated the embedded OCT device using a drive shaft located within the tether sheath. The tethered capsule could be safely used on non-sedated patients, and it could be easily passed down the esophagusoesophagus owing to normal swallowing-induced peristaltic force and pulled back manually. However, though manual pullback is convenient and simple compared to motorized control, it does not provide the stability or repeatability required for high-resolution volumetric OCT, such as en-face OCT, otherwise known as C-Scan OCT that produces transverse images beyond the mucosal surface, especially at the low frame rates achievable with the actuation mechanism used. Volumetric OCT was achieved with the tethered capsule developed by Liang et al.ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1364/BOE.6.001146","ISBN":"2156-7085","ISSN":"2156-7085","PMID":"25909001","abstract":"Depth resolved and en face OCT visualization in vivo may have important clinical applications in endoscopy. We demonstrate a high speed, two-dimensional (2D) distal scanning capsule with a micromotor for fast rotary scanning and a pneumatic actuator for precision longitudinal scanning. Longitudinal position measurement and image registration were performed by optical tracking of the pneumatic scanner. The 2D scanning device enables high resolution imaging over a small field of view and is suitable for OCT as well as other scanning microscopies. Large field of view imaging for screening or surveillance applications can also be achieved by proximally pulling back or advancing the capsule while scanning the distal high-speed micromotor. Circumferential en face OCT was demonstrated in living swine at 250 Hz frame rate and 1 MHz A-scan rate using a MEMS tunable VCSEL light source at 1300 nm. Cross-sectional and en face OCT views of the upper and lower gastrointestinal tract were generated with precision distal pneumatic longitudinal actuation as well as proximal manual longitudinal actuation. These devices could enable clinical studies either as an adjunct to endoscopy, attached to an endoscope, or as a swallowed tethered capsule for non-endoscopic imaging without sedation. The combination of ultrahigh speed imaging and distal scanning capsule technology could enable both screening and surveillance applications.","author":[{"dropping-particle":"","family":"Liang","given":"Kaicheng","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Traverso","given":"Giovanni","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lee","given":"Hsiang-Chieh","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ahsen","given":"Osman Oguz","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wang","given":"Zhao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Potsaid","given":"Benjamin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Giacomelli","given":"Michael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jayaraman","given":"Vijaysekhar","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Barman","given":"Ross","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cable","given":"Alex","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mashimo","given":"Hiroshi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Langer","given":"Robert","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fujimoto","given":"James G.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Biomedical Optics Express","id":"ITEM-1","issue":"4","issued":{"date-parts":[["2015","4","1"]]},"page":"1146","title":"Ultrahigh speed en face OCT capsule for endoscopic imaging","type":"article-journal","volume":"6"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>99</sup>","plainTextFormattedCitation":"99","previouslyFormattedCitation":"<sup>99</sup>"},"properties":{"noteIndex":0},"schema":""}99 during in vivo studies on porcine models. The capsule was 12?mm in diameter with a length of ~35?mm. This capsule utilized an OCT device that circumferentially scanned the light from an external source by a microlens that was rotated by an onboard DC micromotor. Longitudinal scanning could be performed by either the manual force applied to the entire capsule via the tether for large field coverage or by distal pneumatic actuation of an internal carriage within a stationary capsule for small field coverage with high stability. An advantage of using an integrated longitudinal scanning stage is the ability to track non-uniformities along the scan trajectory, which facilitates compensation in post-processing. The use of a semi-rigid tether removed the need for peristaltic propulsion as it made manual positioning easier than with the soft tether used by Gora et al.ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1038/nm.3052","ISBN":"1546-170X (Electronic)\\n1078-8956 (Linking)","ISSN":"10788956","PMID":"23314056","abstract":"Here we introduce tethered capsule endomicroscopy, which involves swallowing an optomechanically engineered pill that captures cross-sectional microscopic images of the gut wall at 30 μm (lateral) × 7 μm (axial) resolution as it travels through the digestive tract. Results in human subjects show that this technique rapidly provides three-dimensional, microstructural images of the upper gastrointestinal tract in a simple and painless procedure, opening up new opportunities for screening for internal diseases.","author":[{"dropping-particle":"","family":"Gora","given":"Michalina J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sauk","given":"Jenny S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Carruth","given":"Robert W.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gallagher","given":"Kevin A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Suter","given":"Melissa J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nishioka","given":"Norman S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kava","given":"Lauren E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rosenberg","given":"Mireille","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bouma","given":"Brett E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tearney","given":"Guillermo J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Nature Medicine","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2013","2","13"]]},"page":"238-240","title":"Tethered capsule endomicroscopy enables less invasive imaging of gastrointestinal tract microstructure","type":"article-journal","volume":"19"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>98</sup>","plainTextFormattedCitation":"98","previouslyFormattedCitation":"<sup>98</sup>"},"properties":{"noteIndex":0},"schema":""}98 However, the authors found that the semi-rigid tether made it difficult to achieve smooth longitudinal scanning owing to difficulty in moving the tether at a constant speed of less than a few millimeters per second. Despite these limitations, the tethered OCT capsule achieved an axial resolution of 8.5 ?m in tissue and scanning frequencies of 250 Hz and was able to produce volumetric scans with 1,750 frames over an area of 1.3?mm2 and a depth of 3.5?mm in 7 seconds. Currently, OCT has not been utilized in a wireless capsule format owing to several remaining technical challenges. One issue is the need to replace the external light source with a battery powered light source within the capsule. Another is the need for short image acquisition times for real-time en-face imaging so that that scans can be produced within a capsule subject to peristaltic motion. [H3]Ionizing RadiationIonizing radiation is a high frequency electromagnetic wave or particle, such as x-rays, of sufficient energy to remove an orbital electron from an atom. X-rays and other ionizing radiation can damage or destroy living tissue, so care must be taken to avoid unnecessary or excessive exposure. Alternatively, ionizing radiation can pass through the tissue of the human body and the interaction between this radiation and the tissue can be recorded to generate images of the internal structure of the body. Though Although the development of capsule endoscopy is seen by many as a means of imaging the gastrointestinal tract without the use of ionizing radiationADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.tgie.2015.02.005","ISSN":"10962883","author":[{"dropping-particle":"","family":"Spada","given":"Cristiano","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hassan","given":"Cesare","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Campanale","given":"Mariachiara","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Costamagna","given":"Guido","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Techniques in Gastrointestinal Endoscopy","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2015","1"]]},"page":"19-23","title":"Colon capsule endoscopy","type":"article-journal","volume":"17"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>100</sup>","plainTextFormattedCitation":"100","previouslyFormattedCitation":"<sup>100</sup>"},"properties":{"noteIndex":0},"schema":""}100ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.tgie.2015.02.005","ISSN":"10962883","author":[{"dropping-particle":"","family":"Spada","given":"Cristiano","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hassan","given":"Cesare","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Campanale","given":"Mariachiara","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Costamagna","given":"Guido","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Techniques in Gastrointestinal Endoscopy","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2015","1"]]},"page":"19-23","title":"Colon capsule endoscopy","type":"article-journal","volume":"17"},"uris":["",""]},{"id":"ITEM-2","itemData":{"DOI":"10.1080/01457630902921287","ISSN":"0145-7632","abstract":"The thermal efficiency of microchannel-based heat sinks relies on uniform fluid flow distribution between channels. Maldistribution, whether caused by poor manifold design or blockage of individual microchannels, can lead to hotspots and consequent thermal damage. This work considers design of manifolds for even flow distribution and the effect of channel blockage on the flow. An approximate model was used to evaluate the effect of manifold geometry on the flow distribution, and the results were compared with computational fluid dynamics (CFD) simulation. Various parameters, which influence the flow distribution such as the shape of distributing and collecting manifolds and position of inlet and outlet holes, have been studied for different inlet flow rates. The effect of channel blockage on flow distribution and pressure drop has been investigated. It was found that good agreement between results of the approximate model and results of CFD simulations are shown only for low Reynolds numbers. Results obtained by approximate model and CFD simulations were used to assist design of manifolds for uniform flow distribution between microchannels.","author":[{"dropping-particle":"","family":"Bogojevic","given":"Dario","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sefiane","given":"Khellil","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Walton","given":"Anthony J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Christy","given":"John R. E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cummins","given":"Gerard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lin","given":"Huamao","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Heat Transfer Engineering","id":"ITEM-2","issue":"13","issued":{"date-parts":[["2009","11"]]},"note":"From Duplicate 1 ( Investigation of Flow Distribution in Microchannels Heat Sinks - Bogojevic, Dario; Sefiane, Khellil; Walton, Anthony J.; Christy, John R. E.; Cummins, Gerard; Lin, Huamao )\nAnd Duplicate 3 ( Investigation of Flow Distribution in Microchannels Heat Sinks - Bogojevic, D.; Sefiane, K.; Walton, A.; Christy, J.; Cummins, G.; Lin, H. )\n","page":"1049-1057","publisher":"Taylor & Francis","title":"Investigation of Flow Distribution in Microchannels Heat Sinks","type":"article-journal","volume":"30"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>101,102</sup>","plainTextFormattedCitation":"101,102","previouslyFormattedCitation":"<sup>101,102</sup>"},"properties":{"noteIndex":0},"schema":""}101,102, the limitation of current, commercially available CE to mucosal imaging has spurred development of a range of capsules capable of sub-mucosal imaging, such as OCT and μUS. The ionizing radiation imaging C-scan system from Check-Cap is the closest to market and has recently gained approval from the FDA for a pilot studyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"URL":"","accessed":{"date-parts":[["2019","1","11"]]},"author":[{"dropping-particle":"","family":"Check-Cap","given":"","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Press Release","id":"ITEM-1","issued":{"date-parts":[["2018"]]},"title":"Check-Cap Announces FDA Conditional Approval of IDE to Initiate U.S. Pilot Study of C-Scan","type":"webpage"},"uris":["",""]}],"mendeley":{"formattedCitation":"<sup>101</sup>","plainTextFormattedCitation":"101","previouslyFormattedCitation":"<sup>101</sup>"},"properties":{"noteIndex":0},"schema":""}101. The C-scan system (Check-Cap, Isfiya, Israel) is an autonomous X-ray-based CE system that includes an external data logger and workstation. The novel aspect of this system is the use of a weak X-ray source to image the colon transmurally; furthermore, because of the nature of this imaging modality, bowel preparation consists solely of ingestion of iodine-based contrast agent taken with normal meals during capsule passageADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1136/gutjnl-2015-310893","ISSN":"14683288","PMID":"26628510","abstract":"MESSAGE The demand for bowel cleansing hampers partici-pation in screening colonoscopy, while poor prep-aration impairs adenoma detection. A novel prepless X-ray imaging capsule for colon screening is presented; the capsule emits low dose X-rays, which are scattered by ingested contrast agent mixed with colon contents, and sensed by detectors in the capsule to generate high-resolution three-dimensional (3D) imagery of the colon without bowel cleansing. Following preliminary studies with implanted polyps in synthetic colon phantoms, bovine cadaver and live swine, and human experi-ments with dummy capsules (n=75), 49 patients swallowed the capsule with natural excretion in 48 after 73.2±45.4 h. Pedunculated and sessile polyps were clearly seen and validated by subsequent col-onoscopy. Total radiation exposure was ultra low (0.03±0.007 mSv). IN MORE DETAIL","author":[{"dropping-particle":"","family":"Gluck","given":"Nathan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shpak","given":"Beni","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Brun","given":"Rita","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"R?sch","given":"Thomas","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Arber","given":"Nadir","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Moshkowitz","given":"Menachem","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gut","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2016","3"]]},"page":"371-373","title":"A novel prepless X-ray imaging capsule for colon cancer screening","type":"article-journal","volume":"65"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1007/s00261-016-1026-y","ISBN":"0026101610","ISSN":"2366-004X","abstract":"? 2017, Springer Science+Business Media New York. Many patients are reluctant to undergo optical colonoscopy for colorectal cancer screening. The Check-Cap colon imaging system is a non-invasive test that comprises an ingestible imaging capsule that emits and detects ultra-low-dose radiation. The capsule generates a 3D reconstruction of the colonic lumen for detection of polyps and cancer. Preliminary preclinical and clinical testing has demonstrated safety and feasibility. Mean radiation dose is estimated at 0.04 mSv. In conclusion, we describe a novel capsule-based, patient-friendly colorectal test that holds potential for non-invasive screening.","author":[{"dropping-particle":"","family":"Kimchy","given":"Yoav","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lifshitz","given":"Ronen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lewkowitz","given":"Shlomo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bertuccio","given":"Guiseppe","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Arber","given":"Nadir","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gluck","given":"Nathan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pickhardt","given":"Perry J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Abdominal Radiology","id":"ITEM-2","issue":"5","issued":{"date-parts":[["2017","5","4"]]},"page":"1291-1297","title":"Radiographic capsule-based system for non-cathartic colorectal cancer screening","type":"article-journal","volume":"42"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>102,103</sup>","plainTextFormattedCitation":"102,103","previouslyFormattedCitation":"<sup>102,103</sup>"},"properties":{"noteIndex":0},"schema":""}102,103 .The C-scan CE device is 11.4 mm in diameter and 34 mm in length. The X-ray source is a short-lived radioisotope, 191Os, with a half-life of 15.4 days, which was chosen to balance the need for a complete examination with environmental concerns regarding device disposal after use. The emitted 65–75 keV X-rays are divided into three rotating beams, enabling a 360o view of the colon wall. Image formation depends on two types of energy returned to the capsule. The first step occurs when emitted photons interact with the ingested iodine contrast agent, producing X-ray fluorescence at a low energy of 27 keV. The second step occurs with Compton scattering [G] of the photons at 52–60 keV. By measuring these two events separately, distances from the capsule to colon can be calculated and wall abnormalities can be detected. The capsule is also equipped with an accelerometer and a magnetometer to enable capsule or pathology localization for follow-up. Acquired data is transmitted wirelessly to external receivers located on the patient, and the system is completed by a workstation that enables a number of 2D and 3D image reconstructionsADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1007/s00261-016-1026-y","ISBN":"0026101610","ISSN":"2366-004X","abstract":"? 2017, Springer Science+Business Media New York. Many patients are reluctant to undergo optical colonoscopy for colorectal cancer screening. The Check-Cap colon imaging system is a non-invasive test that comprises an ingestible imaging capsule that emits and detects ultra-low-dose radiation. The capsule generates a 3D reconstruction of the colonic lumen for detection of polyps and cancer. Preliminary preclinical and clinical testing has demonstrated safety and feasibility. Mean radiation dose is estimated at 0.04 mSv. In conclusion, we describe a novel capsule-based, patient-friendly colorectal test that holds potential for non-invasive screening.","author":[{"dropping-particle":"","family":"Kimchy","given":"Yoav","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lifshitz","given":"Ronen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lewkowitz","given":"Shlomo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bertuccio","given":"Guiseppe","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Arber","given":"Nadir","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gluck","given":"Nathan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pickhardt","given":"Perry J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Abdominal Radiology","id":"ITEM-1","issue":"5","issued":{"date-parts":[["2017","5","4"]]},"page":"1291-1297","title":"Radiographic capsule-based system for non-cathartic colorectal cancer screening","type":"article-journal","volume":"42"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1117/12.2254242","ISBN":"978-1-5106-0709-5; 978-1-5106-0710-1","ISSN":"0277-786X","abstract":"An ingestible capsule for colorectal cancer screening, based on ionizing-radiation imaging, has been developed and is in advanced stages of system stabilization and clinical evaluation. The imaging principle allows future patients using this technology to avoid bowel cleansing, and to continue the normal life routine during procedure. The Check-Cap capsule, or C-Scan (R) Cap, imaging principle is essentially based on reconstructing scattered radiation, while both radiation source and radiation detectors reside within the capsule. The radiation source is a custom-made radioisotope encased in a small canister, collimated into rotating beams. While traveling along the human colon, irradiation occurs from within the capsule towards the colon wall. Scattering of radiation occurs both inside and outside the colon segment; some of this radiation is scattered back and detected by sensors onboard the capsule. During procedure, the patient receives small amounts of contrast agent as an addition to his/her normal diet. The presence of contrast agent inside the colon dictates the dominant physical processes to become Compton Scattering and X-Ray Fluorescence (XRF), which differ mainly by the energy of scattered photons. The detector readout electronics incorporates low-noise Single Photon Counting channels, allowing separation between the products of these different physical processes. Separating between radiation energies essentially allows estimation of the distance from the capsule to the colon wall, hence structural imaging of the intraluminal surface. This allows imaging of structural protrusions into the colon volume, especially focusing on adenomas that may develop into colorectal cancer.","author":[{"dropping-particle":"","family":"Lifshitz","given":"Ronen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kimchy","given":"Yoav","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gelbard","given":"Nir","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leibushor","given":"Avi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Golan","given":"Oleg","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Elgali","given":"Avner","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hassoon","given":"Salah","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kaplan","given":"Max","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Smirnov","given":"Michael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shpigelman","given":"Boaz","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bar-Ilan","given":"Omer","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rubin","given":"Daniel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ovadia","given":"Alex","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"SPIE Physics of Medical Imaging","editor":[{"dropping-particle":"","family":"Flohr","given":"Thomas G.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lo","given":"Joseph Y.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gilat Schmidt","given":"Taly","non-dropping-particle":"","parse-names":false,"suffix":""}],"id":"ITEM-2","issued":{"date-parts":[["2017","3","9"]]},"page":"101321O","title":"An x-ray-based capsule for colorectal cancer screening incorporating single photon counting technology","type":"paper-conference","volume":"10132"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>103,104</sup>","plainTextFormattedCitation":"103,104","previouslyFormattedCitation":"<sup>103,104</sup>"},"properties":{"noteIndex":0},"schema":""}103,104. A pilot study consisting of 46 individuals between 45 and -68 years of age of unknown gastrointestinal status and assumed to be healthy was used to assessassessed the functioning C-scan deviceADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1136/gutjnl-2015-310893","ISSN":"14683288","PMID":"26628510","abstract":"MESSAGE The demand for bowel cleansing hampers partici-pation in screening colonoscopy, while poor prep-aration impairs adenoma detection. A novel prepless X-ray imaging capsule for colon screening is presented; the capsule emits low dose X-rays, which are scattered by ingested contrast agent mixed with colon contents, and sensed by detectors in the capsule to generate high-resolution three-dimensional (3D) imagery of the colon without bowel cleansing. Following preliminary studies with implanted polyps in synthetic colon phantoms, bovine cadaver and live swine, and human experi-ments with dummy capsules (n=75), 49 patients swallowed the capsule with natural excretion in 48 after 73.2±45.4 h. Pedunculated and sessile polyps were clearly seen and validated by subsequent col-onoscopy. Total radiation exposure was ultra low (0.03±0.007 mSv). IN MORE DETAIL","author":[{"dropping-particle":"","family":"Gluck","given":"Nathan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shpak","given":"Beni","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Brun","given":"Rita","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"R?sch","given":"Thomas","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Arber","given":"Nadir","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Moshkowitz","given":"Menachem","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gut","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2016","3"]]},"page":"371-373","title":"A novel prepless X-ray imaging capsule for colon cancer screening","type":"article-journal","volume":"65"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>102</sup>","plainTextFormattedCitation":"102","previouslyFormattedCitation":"<sup>102</sup>"},"properties":{"noteIndex":0},"schema":""}102. A parallel study performed on volunteers, aged 41-70 with no known gastrointestinal pathology, involveding the swallowing of a non-functioning capsule was, used to assess device safetyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1136/gutjnl-2015-310893","ISSN":"14683288","PMID":"26628510","abstract":"MESSAGE The demand for bowel cleansing hampers partici-pation in screening colonoscopy, while poor prep-aration impairs adenoma detection. A novel prepless X-ray imaging capsule for colon screening is presented; the capsule emits low dose X-rays, which are scattered by ingested contrast agent mixed with colon contents, and sensed by detectors in the capsule to generate high-resolution three-dimensional (3D) imagery of the colon without bowel cleansing. Following preliminary studies with implanted polyps in synthetic colon phantoms, bovine cadaver and live swine, and human experi-ments with dummy capsules (n=75), 49 patients swallowed the capsule with natural excretion in 48 after 73.2±45.4 h. Pedunculated and sessile polyps were clearly seen and validated by subsequent col-onoscopy. Total radiation exposure was ultra low (0.03±0.007 mSv). IN MORE DETAIL","author":[{"dropping-particle":"","family":"Gluck","given":"Nathan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shpak","given":"Beni","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Brun","given":"Rita","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"R?sch","given":"Thomas","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Arber","given":"Nadir","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Moshkowitz","given":"Menachem","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gut","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2016","3"]]},"page":"371-373","title":"A novel prepless X-ray imaging capsule for colon cancer screening","type":"article-journal","volume":"65"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>102</sup>","plainTextFormattedCitation":"102","previouslyFormattedCitation":"<sup>102</sup>"},"properties":{"noteIndex":0},"schema":""}102. Preparation for examination involved daily ingestion of up to 50–70 ml iodine solution with food until the capsule had transited. One patient experienced a retained capsule in the caecum that was retrieved via conventional colonoscopy during the scheduled follow-up. No other adverse events were reported. The average radiation dose per patient was calculated to be 0.03±0.0007 mSv; for comparison, a typical effective dose for a posterior to anterior chest x-ray is 0.02 mSvADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"URL":"","accessed":{"date-parts":[["2018","4","26"]]},"author":[{"dropping-particle":"","family":"US Food and Drug Administration","given":"","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"FDA Website","id":"ITEM-1","issued":{"date-parts":[["0"]]},"title":"What are the Radiation Risks from CT ?","type":"webpage"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>105</sup>","plainTextFormattedCitation":"105","previouslyFormattedCitation":"<sup>105</sup>"},"properties":{"noteIndex":0},"schema":""}105 and the dose for a similar 3D CT colonography image is ~8.8 mSv, with the specific dose dependent upon the performing instituteADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1148/radiol.2241011126","ISBN":"0033-8419 (Print)\\n0033-8419 (Linking)","ISSN":"0033-8419","PMID":"12091658","abstract":"PURPOSE: To investigate the sensitivity and specificity of polyp detection and the image quality of computed tomographic (CT) colonography at different radiation dose levels and to study effective doses reported in literature on CT colonography. MATERIALS AND METHODS: CT colonography and colonoscopy were performed with 100 mAs in 50 consecutive patients at high risk for colorectal cancer; 50- and 30-mAs CT colonographic examinations were simulated with controlled addition of noise to raw transmission measurements. One radiologist randomly evaluated all original and simulated images for the presence of polyps and scored image quality. Differences in image quality were assessed with the Wilcoxon rank test. Scan protocols from the literature and recent (unpublished) updates were collected. RESULTS: In nine of 10 patients with polyps 5 mm in diameter or larger (sensitivity, 90%) and in seven of 17 patients with polyps smaller than 5 mm, polyps were correctly identified with CT colonography at all dose levels. Specificity for patients without polyps 5 mm or larger was 53%-60% at all dose levels and for patients without any polyps was 26% (at 100 and 50 mAs) and 48% (at 30 mAs). Image quality decreased significantly as the dose level decreased. The median effective doses (supine and prone positions) calculated from protocols reported in the literature and updates were 7.8 and 8.8 mSv, respectively. CONCLUSION: Although image quality decreases significantly at 30 mAs (3.6 mSv), polyp detection remains unimpaired. The median dose for CT colonography at institutions that perform CT colonographic research is currently 8.8 mSv.","author":[{"dropping-particle":"","family":"Gelder","given":"Rogier E.","non-dropping-particle":"van","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Venema","given":"Henk W.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Serlie","given":"Iwo W. O.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nio","given":"C. Yung","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Determann","given":"Rogier M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tipker","given":"Corinne A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Vos","given":"Frans M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Glas","given":"Afina S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bartelsman","given":"Joep F. W.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bossuyt","given":"Patrick M. M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Laméris","given":"Johan S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stoker","given":"Jaap","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Radiology","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2002"]]},"page":"25-33","title":"CT Colonography at Different Radiation Dose Levels: Feasibility of Dose Reduction","type":"article-journal","volume":"224"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>106</sup>","plainTextFormattedCitation":"106","previouslyFormattedCitation":"<sup>106</sup>"},"properties":{"noteIndex":0},"schema":""}106. The detection of pedunculated and sessile polyps, as confirmed by subsequent standard colonoscopy, was reported. Despite the lack of quantitative human data, in vivo pig trial results indicated the device had sufficient resolution to detect 5 mm diameter implanted silicone beadsADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1136/gutjnl-2015-310893","ISSN":"14683288","PMID":"26628510","abstract":"MESSAGE The demand for bowel cleansing hampers partici-pation in screening colonoscopy, while poor prep-aration impairs adenoma detection. A novel prepless X-ray imaging capsule for colon screening is presented; the capsule emits low dose X-rays, which are scattered by ingested contrast agent mixed with colon contents, and sensed by detectors in the capsule to generate high-resolution three-dimensional (3D) imagery of the colon without bowel cleansing. Following preliminary studies with implanted polyps in synthetic colon phantoms, bovine cadaver and live swine, and human experi-ments with dummy capsules (n=75), 49 patients swallowed the capsule with natural excretion in 48 after 73.2±45.4 h. Pedunculated and sessile polyps were clearly seen and validated by subsequent col-onoscopy. Total radiation exposure was ultra low (0.03±0.007 mSv). IN MORE DETAIL","author":[{"dropping-particle":"","family":"Gluck","given":"Nathan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shpak","given":"Beni","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Brun","given":"Rita","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"R?sch","given":"Thomas","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Arber","given":"Nadir","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Moshkowitz","given":"Menachem","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gut","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2016","3"]]},"page":"371-373","title":"A novel prepless X-ray imaging capsule for colon cancer screening","type":"article-journal","volume":"65"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>102</sup>","plainTextFormattedCitation":"102","previouslyFormattedCitation":"<sup>102</sup>"},"properties":{"noteIndex":0},"schema":""}102. As stated by the authors, further validation and direct comparison of the system with standard colonoscopy is requiredADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1136/gutjnl-2015-310893","ISSN":"14683288","PMID":"26628510","abstract":"MESSAGE The demand for bowel cleansing hampers partici-pation in screening colonoscopy, while poor prep-aration impairs adenoma detection. A novel prepless X-ray imaging capsule for colon screening is presented; the capsule emits low dose X-rays, which are scattered by ingested contrast agent mixed with colon contents, and sensed by detectors in the capsule to generate high-resolution three-dimensional (3D) imagery of the colon without bowel cleansing. Following preliminary studies with implanted polyps in synthetic colon phantoms, bovine cadaver and live swine, and human experi-ments with dummy capsules (n=75), 49 patients swallowed the capsule with natural excretion in 48 after 73.2±45.4 h. Pedunculated and sessile polyps were clearly seen and validated by subsequent col-onoscopy. Total radiation exposure was ultra low (0.03±0.007 mSv). IN MORE DETAIL","author":[{"dropping-particle":"","family":"Gluck","given":"Nathan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shpak","given":"Beni","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Brun","given":"Rita","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"R?sch","given":"Thomas","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Arber","given":"Nadir","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Moshkowitz","given":"Menachem","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gut","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2016","3"]]},"page":"371-373","title":"A novel prepless X-ray imaging capsule for colon cancer screening","type":"article-journal","volume":"65"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>102</sup>","plainTextFormattedCitation":"102","previouslyFormattedCitation":"<sup>102</sup>"},"properties":{"noteIndex":0},"schema":""}102. [h2]Biophysical Measurements Changes in gastrointestinal activity, such as transit time can indicate a pathological condition. To aid this situation several groups have adapted CE to measure changes in physical parameters of the gastrointestinal tract, such as pressure and myoelectric activity. Ingestible capsules to measure other physical parameters, such as temperature, have also been developed for sports medicine rather than gastroenterology and are described here. [H3]Temperature CorTemp by HQ (Palmetto, FL, USA) is an FDA-approved, wireless capsule that measures internal body temperature with an accuracy of ± 0.1°C. Applications for monitoring internal body temperature are found in several areas, such as sports physiology, firefighting, research and medicine, occupational safety and militaryADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1007/s00484-013-0687-2","ISSN":"0020-7128","author":[{"dropping-particle":"","family":"Niedermann","given":"Reto","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wyss","given":"Eva","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Annaheim","given":"Simon","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Psikuta","given":"Agnes","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Davey","given":"Sarah","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rossi","given":"René Michel","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"International Journal of Biometeorology","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2014","1","13"]]},"page":"7-15","title":"Prediction of human core body temperature using non-invasive measurement methods","type":"article-journal","volume":"58"},"uris":["",""]}],"mendeley":{"formattedCitation":"<sup>107</sup>","plainTextFormattedCitation":"107","previouslyFormattedCitation":"<sup>107</sup>"},"properties":{"noteIndex":0},"schema":""}107,ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1371/journal.pone.0083740","ISBN":"1932-6203 (Electronic)\\n1932-6203 (Linking)","ISSN":"1932-6203","PMID":"24586228","abstract":"Explosive ordnance disposal (EOD) technicians are required to wear protective clothing to protect themselves from the threat of overpressure, fragmentation, impact and heat. The engineering requirements to minimise these threats results in an extremely heavy and cumbersome clothing ensemble that increases the internal heat generation of the wearer, while the clothing's thermal properties reduce heat dissipation. This study aimed to evaluate the heat strain encountered wearing EOD protective clothing in simulated environmental extremes across a range of differing work intensities. Eight healthy males [age 25 ± 6 years (mean ± sd), height 180 ± 7 cm, body mass 79 ± 9 kg, VO2max 57 ± 6 ml(.) kg(-1.)min(-1)] undertook nine trials while wearing an EOD9 suit (weighing 33.4 kg). The trials involved walking on a treadmill at 2.5, 4 and 5.5 km ? h(-1) at each of the following environmental conditions, 21, 30 and 37 °C wet bulb globe temperature (WBGT) in a randomised controlled crossover design. The trials were ceased if the participants' core temperature reached 39 °C, if heart rate exceeded 90% of maximum, if walking time reached 60 minutes or due to fatigue/nausea. Tolerance times ranged from 10-60 minutes and were significantly reduced in the higher walking speeds and environmental conditions. In a total of 15 trials (21%) participants completed 60 minutes of walking; however, this was predominantly at the slower walking speeds in the 21 °C WBGT environment. Of the remaining 57 trials, 50 were ceased, due to attainment of 90% maximal heart rate. These near maximal heart rates resulted in moderate-high levels of physiological strain in all trials, despite core temperature only reaching 39 °C in one of the 72 trials.","author":[{"dropping-particle":"","family":"Stewart","given":"Ian B.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stewart","given":"Kelly L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Worringham","given":"Charles J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Costello","given":"Joseph T.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"PLoS ONE","editor":[{"dropping-particle":"","family":"Hug","given":"Fran?ois","non-dropping-particle":"","parse-names":false,"suffix":""}],"id":"ITEM-1","issue":"2","issued":{"date-parts":[["2014","2","21"]]},"page":"e83740","title":"Physiological Tolerance Times while Wearing Explosive Ordnance Disposal Protective Clothing in Simulated Environmental Extremes","type":"article-journal","volume":"9"},"uris":["",""]}],"mendeley":{"formattedCitation":"<sup>108</sup>","plainTextFormattedCitation":"108","previouslyFormattedCitation":"<sup>108</sup>"},"properties":{"noteIndex":0},"schema":""}108. These devices have not been used for the diagnosis of GI disease due owing to the non-specific nature of temperature changes as a biomarker. One capsule that has been used in the diagnosis of GI disease is the SmartPill (Medtronic, Yoqneam, Israel), which along with an integrated pH and pressure sensor also incorporates a temperature sensor, though this is used, in conjunction with the other sensors, to aid the measurement of transit time through the various regions of the GI tract. The temperature sensor has a range of 20–40OC with an accuracy of ± 1OC and is measured at a frequency of 0.05 Hz. This capsule is discussed in greater detail in the section describing pH-sensing capsules. [H3]Manometry Consumed food is moved along the GI tract via the periodic peristaltic contraction of muscles in the esophagusoesophagus, stomach, small and large intestines. During and after consumption, highly irregular contractions mix the food and digestive enzymes in the small intestine while slowly moving them towards the large intestine. These contractions are defined as the motility of the gastrointestinal tract. An estimated 40% of gastrointestinal conditions worldwide are associated with abnormal gastrointestinal motility (dysmotility), resulting in abdominal discomfort, pain and other intestinal problems for 20% of the general populationADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1053/j.gastro.2007.06.010","ISSN":"00165085","author":[{"dropping-particle":"","family":"Halder","given":"Smita L.S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Locke","given":"G. Richard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schleck","given":"Cathy D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zinsmeister","given":"Alan R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Melton","given":"L. Joseph","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Talley","given":"Nicholas J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastroenterology","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2007","9"]]},"page":"799-807.e1","title":"Natural History of Functional Gastrointestinal Disorders: A 12-year Longitudinal Population-Based Study","type":"article-journal","volume":"133"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1111/j.1365-2982.2008.01097.x","ISSN":"1350-1925","author":[{"dropping-particle":"","family":"Talley","given":"N. J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Neurogastroenterology & Motility","id":"ITEM-2","issue":"s1","issued":{"date-parts":[["2008","5"]]},"page":"121-129","title":"Functional gastrointestinal disorders as a public health problem","type":"article-journal","volume":"20"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>109,110</sup>","plainTextFormattedCitation":"109,110","previouslyFormattedCitation":"<sup>109,110</sup>"},"properties":{"noteIndex":0},"schema":""}109,110. For example, small intestine dysmotility may be symptomatic of irritable bowel syndrome, gastroparesis and chronic idiopathic constipationADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1046/j.1365-2982.1999.00147.x","ISBN":"1365-2982","ISSN":"1350-1925","PMID":"10354340","abstract":"The physiology and pathophysiology of small bowel motility are reviewed with particular focus on the motility patterns and periods that are detected by intraluminal manometry. Motility patterns are groups of phasic pressure waves resulting from contractions of the circular muscle layer of the small bowel that are organized by the enteric nervous system. Phase III of the migrating motor complex, the hallmark of the fasting motility period, thus reflects enteric neuromuscular function. Response to meal challenge also involves the CNS, reflexes beyond the gut and endocrine responses. Although specific disease diagnosis cannot be made by motility studies of the small bowel, the functional integrity is revealed. The normal occurrence of the essential patterns and periods of motility and the absence of distinctly abnormal patterns evidence preserved function, whereas the opposite indicates clinically significant dysmotility. Certain motility patterns are occasionally seen both in health and disease, and increased prevalence indicates a moderate dysfunction of yet unclear significance. Bacterial overgrowth with Gram-negative bacilli is the consequence of severe small bowel dysmotility, and a diagnosis that can be predicted by a motility study. Testing can be useful in the clinical management of paediatric and adult patients also by predicting the prognosis and response to enteral nutrition and medical therapy. Further studies are, however, needed to take full advantage of motility testing in clinical practise.","author":[{"dropping-particle":"","family":"Husebye","given":"Einar","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Neurogastroenterology and Motility","id":"ITEM-1","issue":"3","issued":{"date-parts":[["1999","6"]]},"page":"141-161","title":"The patterns of small bowel motility: physiology and implications in organic disease and functional disorders","type":"article-journal","volume":"11"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>111</sup>","plainTextFormattedCitation":"111","previouslyFormattedCitation":"<sup>111</sup>"},"properties":{"noteIndex":0},"schema":""}111. However, why and how dysmotility occurs is not fully understood.Current methods of diagnosing dysmotility include serosally attached electrodes, barium X-ray imaging, scintigraphic imaging and electrogastrographyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/apt.12496","ISBN":"0269-2813\\r1365-2036","ISSN":"02692813","PMID":"24102305","abstract":"BACKGROUND: The characterisation and management of chronic severe gastrointestinal (GI) dysmotility are challenging. It may cause intestinal failure requiring home parenteral nutrition (HPN).\\n\\nAIMS: To review the presentation, aetiology, characterisation, management and outcome of chronic severe GI dysmotility, and to suggest a pragmatic management algorithm.\\n\\nMETHODS: PubMed search was performed up to December 2012 using appropriate search terms, restricted to human articles and reviewed for relevance. Segmental dysmotility, acute ileus, functional syndromes and non-English articles were excluded. Evidence and recommendations were evaluated using the GRADE system.\\n\\nRESULTS: In total, 721 relevant articles were reviewed. A coherent and definitive picture is hampered by overlapping classification systems using multi-modal characterisation methods, subject to pitfalls and some requiring further validation. The literature is confined to case series with no randomised trials. Fewer than 20% undergo full thickness jejunal biopsy, which are otherwise labelled idiopathic. However, in studies with up to 80% biopsy rates, neuromuscular abnormalities may be found in 90%. Between 14% and 50% will require HPN, comprising 8-14% of all HPN patients, of which 2/3 are primary/idiopathic and 1/3 secondary, with scleroderma being the leading secondary cause. Ten-year mortality ranges from 13% to 35% and is worst in elderly scleroderma patients. Management includes limited treatments for secondary causes, prokinetics, symptom palliation, psychological support, nutrition, hydration and judicious surgery.\\n\\nCONCLUSIONS: Severe dysmotility often remains idiopathic. It is rarely possible to alter disease trajectory; consequently, prognosis may be poor. Multi-disciplinary teams in a specialist setting can improve outcomes. Graded recommendations are enumerated and a pragmatic algorithm is suggested.","author":[{"dropping-particle":"","family":"Paine","given":"P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"McLaughlin","given":"J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lal","given":"S.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Alimentary Pharmacology and Therapeutics","id":"ITEM-1","issued":{"date-parts":[["2013"]]},"title":"Review article: The assessment and management of chronic severe gastrointestinal dysmotility in adults","type":"article"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>112</sup>","plainTextFormattedCitation":"112","previouslyFormattedCitation":"<sup>112</sup>"},"properties":{"noteIndex":0},"schema":""}112. Endoscopic manometry is a commonly used procedure; this technique involves transnasal insertion of a modified catheter containing a series of pressure sensors into the small intestine. The pressure sensors record the contractile behavior of the gastrointestinal tract for subsequent clinical assessmentADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1053/j.gastro.2004.11.008","ISBN":"0016-5085","ISSN":"00165085","PMID":"15633138","abstract":"This literature review and the recommendations therein were prepared for the American Gastroenterological Association Clinical Practice Committee. The paper was approved by the Committee on October 2, 2004, and by the AGA Governing Board on November 7, 2004.","author":[{"dropping-particle":"","family":"Pandolfino","given":"John E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kahrilas","given":"Peter J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastroenterology","id":"ITEM-1","issued":{"date-parts":[["2005"]]},"title":"AGA technical review on the clinical use of esophageal manometry","type":"article"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>113</sup>","plainTextFormattedCitation":"113","previouslyFormattedCitation":"<sup>113</sup>"},"properties":{"noteIndex":0},"schema":""}113 . As with many endoscopic procedures, manometry can be uncomfortable for patients and most of the small intestine cannot easily be reached. Other methods use balloons to measure the motion of the bowel wall, electropotential recordings associated with peristaltic activity and abdominal acoustic emissions have been found to be imprecise compared with endoscopic manometryADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.medengphy.2004.11.002","ISBN":"1350-4533","ISSN":"13504533","PMID":"15863344","abstract":"Telemetry capsules have existed since the 1950s and were used to measure temperature, pH or pressure inside the gastrointestinal (GI) tract. It was hoped that these capsules would replace invasive techniques in the diagnosis of function disorders in the GI tract. However, problems such as signal loss and uncertainty of the pills position limited their use in a clinical setting. In this paper, a review of the capabilities of MicroElectroMechanical Systems (MEMS) and thick film technology (TFT) for the fabrication of a wireless pressure sensing microsystem is presented. The circuit requirements and methods of data transfer are examined. The available fabrication methods for MEMS sensors are also discussed and examples of wireless sensors are given. Finally the limitations of each technology are examined. ?? 2004 IPEM. Published by Elsevier Ltd. All rights reserved.","author":[{"dropping-particle":"","family":"Arshak","given":"A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Arshak","given":"K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Waldron","given":"D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Morris","given":"D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Korostynska","given":"O.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jafer","given":"E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lyons","given":"G.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Medical Engineering and Physics","id":"ITEM-1","issue":"5","issued":{"date-parts":[["2005"]]},"page":"347-356","title":"Review of the potential of a wireless MEMS and TFT microsystems for the measurement of pressure in the GI tract","type":"article-journal","volume":"27"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>114</sup>","plainTextFormattedCitation":"114","previouslyFormattedCitation":"<sup>114</sup>"},"properties":{"noteIndex":0},"schema":""}114. A minimally invasive, reliable and versatile diagnostic tool is therefore an attractive development target for the detection and accurate characterization of gastrointestinal tract dysmotility. Ingestible motility capsules (IMCs) offer an attractive alternative to other test modalities as they provide real-time in-situ information about the environment of the gastrointestinal tract, such as pressure, temperature, pH, transit time and potentially capsule location, without the need for ionizing radiation or discomfort to the patient. The acquisition of the gastrointestinal pressure profile via an IMC could replace conventional antroduodenal and colonic studies that use invasive and less well-tolerated manometric catheters to quantify the contractile pressure patterns. Assessment of the pressure profile captured by a motility capsule has the potential to provide richer motility information beyond that currently recordedADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"PMID":"24049848","abstract":"The information in this report is intended to help health care decisionmakers—patients and clinicians, health system leaders, and policymakers, among others—make well informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients.","author":[{"dropping-particle":"","family":"Stein","given":"E","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Berger","given":"Z","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hutfless","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shah","given":"L","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Comparative Effectiveness Review","id":"ITEM-1","issue":"110","issued":{"date-parts":[["2013"]]},"title":"Wireless motility capsule versus other diagnostic technologies for evaluating gastroparesis and constipation: a comparative effectiveness review","type":"article-journal"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>115</sup>","plainTextFormattedCitation":"115","previouslyFormattedCitation":"<sup>115</sup>"},"properties":{"noteIndex":0},"schema":""}115. The SmartPill is the only FDA-approved, wireless CE device with pressure sensing capabilities currently on the marketADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"ISBN":"7349367392","ISSN":"15547914","PMID":"22347818","abstract":"The wireless motility/pH capsule (WMC) is an orally ingested, nondigestible, data recording device that enables the simultaneous assessment of regional and whole gut transit. Approved by the US Food and Drug Administration for the evaluation of patients with suspected delayed gastric emptying and the evaluation of colonic transit time in patients with chronic idiopathic constipation, this capsule continuously measures the temperature, pH, and pressure of its surrounding environment while traveling through the gastrointestinal tract (via gut peristalsis) until exiting the body through the anus. Validated patterns in pH and temperature recordings allow for accurate measurement of gastric emptying, small bowel transit, colonic transit, and whole gut transit times. The WMC is a nonradioactive, office-based, gastrointestinal transit testing modality shown in several clinical trials to be a suitable alternative to scintigraphy and radiopaque marker studies in measuring gastric emptying, small bowel, colonic, and whole gut transit times. Unlike widely available transit tests, which provide only region-specific transit data, the WMC offers the benefit of measuring gastric, small bowel, and colonic transit times in a single examination. The WMC also provides intraluminal pressure readings throughout the digestive tract, offering a noninvasive means by which to assess gastrointestinal motility. The WMC should be considered the transit study of choice for individuals suspected of having altered transit in more than one region of the gastrointestinal tract. This review summarizes the features and performance characteristics of the WMC as well as provides a summary on how this diagnostic modality is most effectively used in the assessment of gastrointestinal symptom complexes due to suspected abnormalities in transit.","author":[{"dropping-particle":"","family":"Saad","given":"Richard J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hasler","given":"William L.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastroenterology and Hepatology","id":"ITEM-1","issue":"12","issued":{"date-parts":[["2011"]]},"page":"795-804","title":"A technical review and clinical assessment of the wireless motility capsule","type":"bill","volume":"7"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>116</sup>","plainTextFormattedCitation":"116","previouslyFormattedCitation":"<sup>116</sup>"},"properties":{"noteIndex":0},"schema":""}116. SmartPill contains a temperature sensor (25–49oC), a pH sensor (pH 0.059.0), a single pressure sensor with an operating range 0–46 kPa and a sensitivity of ±0.650 kPa that can record the pressure of its environment, and an internal antenna that can transmit captured data wirelessly in real time at 433 MHz. The capsule is enclosed in a non-digestible polyurethane shell, battery powered, and is intended for single use. The SmartPill can be used to measure gastric emptying time and small bowel, colon and whole gut transit times by evaluating combined pressure, pH and temperature profiles. Though studies have utilized the SmartPill to diagnose gastroparesisADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/j.1365-2982.2010.01468.x","ISSN":"13501925","author":[{"dropping-particle":"","family":"Kloetzer","given":"L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chey","given":"w. d.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mccallum","given":"r. w.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Koch","given":"k. l.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wo","given":"j. m.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sitrin","given":"M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Katz","given":"l. a.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lackner","given":"j. m.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Parkman","given":"h. p.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wilding","given":"g. e.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Semler","given":"j. r.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hasler","given":"w. l.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kuo","given":"B.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Neurogastroenterology & Motility","id":"ITEM-1","issued":{"date-parts":[["2010","1"]]},"title":"Motility of the antroduodenum in healthy and gastroparetics characterized by wireless motility capsule","type":"article-journal"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>117</sup>","plainTextFormattedCitation":"117","previouslyFormattedCitation":"<sup>117</sup>"},"properties":{"noteIndex":0},"schema":""}117 and chronic idiopathic constipationADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1152/ajpgi.00136.2009","ISSN":"0193-1857","author":[{"dropping-particle":"","family":"Hasler","given":"William L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Saad","given":"Richard J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rao","given":"Satish S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wilding","given":"Gregory E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Parkman","given":"Henry P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Koch","given":"Kenneth L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"McCallum","given":"Richard W.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kuo","given":"Braden","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sarosiek","given":"Irene","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sitrin","given":"Michael D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Semler","given":"John R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chey","given":"William D.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"American Journal of Physiology-Gastrointestinal and Liver Physiology","id":"ITEM-1","issue":"6","issued":{"date-parts":[["2009","12"]]},"page":"G1107-G1114","title":"Heightened colon motor activity measured by a wireless capsule in patients with constipation: relation to colon transit and IBS","type":"article-journal","volume":"297"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>118</sup>","plainTextFormattedCitation":"118","previouslyFormattedCitation":"<sup>118</sup>"},"properties":{"noteIndex":0},"schema":""}118, the presence of a single pressure sensor does not provide sufficient manometric information as it records only the intraluminal pressure in the gastrointestinal tract and is unable to provide information on peristaltic behaviourADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/TBME.2015.2444406","ISBN":"0018-9294 VO - 62","ISSN":"15582531","PMID":"26080374","abstract":"A tethered pressure measurement capsule was developed for measuring the small intestine contraction pressure to assist in locating capsules within the gastrointestinal (GI) tract and quantifying the contact force between the capsule and the small intestine lumen. The capsule was calibrated statically and dynamically in depth-controlled water at body temperature (37-38?°C). In vitro tests were performed on an intestinal simulator to verify the measurement function of the capsule. To perform a preliminary evaluation of its pressure measuring capabilities, the capsule was tested at a single location in a live pig model. The pressure signal from the live animal test was analyzed in the time domain, and then, the empirical mode decomposition and fast Fourier transformation were applied to analyze the contraction pressure and ambient pressure in the frequency domain. The contraction rate was 9.4 to 11.0?times per minute. The peak value of the contraction pressure was 0.24 ± 0.05 kPa. The successful test of this prototype lays the groundwork for a future untethered, swallowable version of the capsule, which will be capable of measuring dynamic pressures while in transit.","author":[{"dropping-particle":"","family":"Li","given":"Pengbo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kothari","given":"Vishal","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Terry","given":"Benjamin S.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Transactions on Biomedical Engineering","id":"ITEM-1","issue":"11","issued":{"date-parts":[["2015","11"]]},"page":"2702-2708","title":"Design and Preliminary Experimental Investigation of a Capsule for Measuring the Small Intestine Contraction Pressure","type":"article-journal","volume":"62"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1007/s11894-016-0489-x","ISSN":"1522-8037","author":[{"dropping-particle":"","family":"Saad","given":"Richard J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Current Gastroenterology Reports","id":"ITEM-2","issue":"3","issued":{"date-parts":[["2016","3","23"]]},"page":"14","title":"The Wireless Motility Capsule: a One-Stop Shop for the Evaluation of GI Motility Disorders","type":"article-journal","volume":"18"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1111/j.1365-2982.2010.01468.x","ISSN":"13501925","author":[{"dropping-particle":"","family":"Kloetzer","given":"L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chey","given":"w. d.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mccallum","given":"r. w.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Koch","given":"k. l.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wo","given":"j. m.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sitrin","given":"M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Katz","given":"l. a.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lackner","given":"j. m.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Parkman","given":"h. p.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wilding","given":"g. e.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Semler","given":"j. r.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hasler","given":"w. l.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kuo","given":"B.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Neurogastroenterology & Motility","id":"ITEM-3","issued":{"date-parts":[["2010","1"]]},"title":"Motility of the antroduodenum in healthy and gastroparetics characterized by wireless motility capsule","type":"article-journal"},"uris":[""]},{"id":"ITEM-4","itemData":{"ISBN":"7349367392","ISSN":"15547914","PMID":"22347818","abstract":"The wireless motility/pH capsule (WMC) is an orally ingested, nondigestible, data recording device that enables the simultaneous assessment of regional and whole gut transit. Approved by the US Food and Drug Administration for the evaluation of patients with suspected delayed gastric emptying and the evaluation of colonic transit time in patients with chronic idiopathic constipation, this capsule continuously measures the temperature, pH, and pressure of its surrounding environment while traveling through the gastrointestinal tract (via gut peristalsis) until exiting the body through the anus. Validated patterns in pH and temperature recordings allow for accurate measurement of gastric emptying, small bowel transit, colonic transit, and whole gut transit times. The WMC is a nonradioactive, office-based, gastrointestinal transit testing modality shown in several clinical trials to be a suitable alternative to scintigraphy and radiopaque marker studies in measuring gastric emptying, small bowel, colonic, and whole gut transit times. Unlike widely available transit tests, which provide only region-specific transit data, the WMC offers the benefit of measuring gastric, small bowel, and colonic transit times in a single examination. The WMC also provides intraluminal pressure readings throughout the digestive tract, offering a noninvasive means by which to assess gastrointestinal motility. The WMC should be considered the transit study of choice for individuals suspected of having altered transit in more than one region of the gastrointestinal tract. This review summarizes the features and performance characteristics of the WMC as well as provides a summary on how this diagnostic modality is most effectively used in the assessment of gastrointestinal symptom complexes due to suspected abnormalities in transit.","author":[{"dropping-particle":"","family":"Saad","given":"Richard J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hasler","given":"William L.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastroenterology and Hepatology","id":"ITEM-4","issue":"12","issued":{"date-parts":[["2011"]]},"page":"795-804","title":"A technical review and clinical assessment of the wireless motility capsule","type":"bill","volume":"7"},"uris":[""]},{"id":"ITEM-5","itemData":{"DOI":"10.1177/1756283X12437874","ISSN":"1756-283X","author":[{"dropping-particle":"","family":"Tran","given":"Khoa","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Brun","given":"Rita","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kuo","given":"Braden","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Therapeutic Advances in Gastroenterology","id":"ITEM-5","issue":"4","issued":{"date-parts":[["2012","7","30"]]},"page":"249-260","title":"Evaluation of regional and whole gut motility using the wireless motility capsule: relevance in clinical practice","type":"article-journal","volume":"5"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>116,117,119–121</sup>","plainTextFormattedCitation":"116,117,119–121","previouslyFormattedCitation":"<sup>116,117,119–121</sup>"},"properties":{"noteIndex":0},"schema":""}116,117,119–121 unlike conventional manometryADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1177/1756283X12437874","ISBN":"1756-2848 (Electronic)\\r1756-283X (Linking)","ISSN":"1756-2848","PMID":"22778790","abstract":"The wireless motility capsule (WMC) is an ambulatory noninvasive and nonradioactive diagnostic sensor that continuously samples intraluminal pH, temperature, and pressure as it moves through the gastrointestinal (GI) tract. This review summarizes the data obtained in clinical trials with the WMC and discusses its role in clinical practice. The United States Food and Drug Administration has approved the SmartPill GI monitoring system for the evaluation of gastric emptying time in patients with suspected gastroparesis, the evaluation of colonic transit time in patients with suspected chronic constipation, and for the characterization of pressure profiles from the antrum and duodenum. Clinical studies have shown that WMC-measured GI transit times can distinguish patients with motility abnormalities similarly to conventional testing. However, the WMC offers the advantage of providing a full GI-tract profile, enabling the detection of multiregional GI transit abnormalities in patients with suspected upper or lower GI dysmotility. The WMC also characterizes pressure profiles of the GI tract and impaired pressure profile limits are reported for the antrum and duodenum. In comparison with manometry, interpretations of pressure measurements obtained by the WMC are limited by an inability to detect a peristaltic pressure wave front, and further investigation is required to develop clinical applications. Clinical studies with the WMC indicated that it should be considered for the evaluation of regional and whole gut transit time in patients with suspected upper or lower dysmotility, particularly if there are concerns about multiregional dysmotility.","author":[{"dropping-particle":"","family":"Tran","given":"Khoa","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Brun","given":"Rita","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kuo","given":"Braden","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Therapeutic advances in gastroenterology","id":"ITEM-1","issue":"4","issued":{"date-parts":[["2012"]]},"page":"249-60","title":"Evaluation of regional and whole gut motility using the wireless motility capsule: relevance in clinical practice.","type":"article-journal","volume":"5"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>122</sup>","plainTextFormattedCitation":"122","previouslyFormattedCitation":"<sup>123</sup>"},"properties":{"noteIndex":0},"schema":""}122. The recommendation by the American and European Neurogastroenterology and Motility societies for the use of SmartPill for regional and whole gut transit time evaluation in individuals with alterations to GI motility in single or multiple regionsADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1097/MCG.0b013e3181ff0122","ISSN":"01920790","PMID":"21135705","abstract":"GOALS: To examine the diagnostic utility of wireless motility capsule (WMC) in patients with suspected gastrointestinal (GI) dysmotility. BACKGROUND: Subjects with suspected GI motility disorders undergo invasive and expensive diagnostic tests. In these patients, whether WMC provides clinically useful information is unknown. STUDY: Patients with symptoms of dysmotility and normal endoscopic/radiologic evaluations were assessed with WMC test and conventional motility tests (CMT). Diagnostic utility of WMC was assessed retrospectively by examining device agreement and new information compared with CMT. RESULTS: On the basis of predominant symptom(s), 86 patients were classified into 2 subgroups: lower GI (LGI=50) and upper GI (UGI=36). Clinical suspicion was confirmed in 52% and 66% of patients, respectively, and there was good device agreement between WMC and CMT in 76% and 81% in the LGI and UGI groups, respectively. There was new diagnostic information with the WMC test in 53% of the LGI (P=0.006) and 47% of the UGI group (P=0.001). WMC detected generalized motility disorder in 44 (51%) patients and influenced management in 30% of LGI and 50% of UGI subjects. CONCLUSIONS: WMC confirmed clinical suspicion, provided new diagnostic information, influenced clinical management, and detected many patients with generalized motility disorder. It had good device agreement with conventional tests.","author":[{"dropping-particle":"","family":"Rao","given":"Satish S.C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mysore","given":"Krupa","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Attaluri","given":"Ashok","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Valestin","given":"Jessica","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Clinical Gastroenterology","id":"ITEM-1","issued":{"date-parts":[["2011"]]},"title":"Diagnostic utility of wireless motility capsule in gastrointestinal dysmotility","type":"article-journal"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>122</sup>","plainTextFormattedCitation":"122","previouslyFormattedCitation":"<sup>123</sup>"},"properties":{"noteIndex":0},"schema":""}122 can be predominantly attributed to the multimodal approach of using the pH, pressure and temperature sensor data together. Recording both contractile and intraluminal pressure requires an array of pressure sensors arranged longitudinally and radially around the capsule that are sensitive to pressure changes of less than< 0.133 kPa and can operate between 0 and 25 kPa are required to capture the weak peristaltic or segmentation contraction of the GI tractADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/TBME.2015.2444406","ISBN":"0018-9294 VO - 62","ISSN":"15582531","PMID":"26080374","abstract":"A tethered pressure measurement capsule was developed for measuring the small intestine contraction pressure to assist in locating capsules within the gastrointestinal (GI) tract and quantifying the contact force between the capsule and the small intestine lumen. The capsule was calibrated statically and dynamically in depth-controlled water at body temperature (37-38?°C). In vitro tests were performed on an intestinal simulator to verify the measurement function of the capsule. To perform a preliminary evaluation of its pressure measuring capabilities, the capsule was tested at a single location in a live pig model. The pressure signal from the live animal test was analyzed in the time domain, and then, the empirical mode decomposition and fast Fourier transformation were applied to analyze the contraction pressure and ambient pressure in the frequency domain. The contraction rate was 9.4 to 11.0?times per minute. The peak value of the contraction pressure was 0.24 ± 0.05 kPa. The successful test of this prototype lays the groundwork for a future untethered, swallowable version of the capsule, which will be capable of measuring dynamic pressures while in transit.","author":[{"dropping-particle":"","family":"Li","given":"Pengbo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kothari","given":"Vishal","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Terry","given":"Benjamin S.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Transactions on Biomedical Engineering","id":"ITEM-1","issue":"11","issued":{"date-parts":[["2015","11"]]},"page":"2702-2708","title":"Design and Preliminary Experimental Investigation of a Capsule for Measuring the Small Intestine Contraction Pressure","type":"article-journal","volume":"62"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>119</sup>","plainTextFormattedCitation":"119","previouslyFormattedCitation":"<sup>119</sup>"},"properties":{"noteIndex":0},"schema":""}119.. Additionally, while not reported for SmartPill, other prototype pressure sensing capsules of a similar design have demonstrated susceptibility are susceptible to interference from respiration and heartbeat that dominates the signal and requires, requiring further filteringADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1115/1.4036260","ISSN":"0148-0731","author":[{"dropping-particle":"","family":"Li","given":"Pengbo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kreikemeier-Bower","given":"Craig","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Xie","given":"Wanchuan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kothari","given":"Vishal","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Terry","given":"Benjamin S.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Biomechanical Engineering","id":"ITEM-1","issue":"5","issued":{"date-parts":[["2017","3","24"]]},"page":"051003","title":"Design of a Wireless Medical Capsule for Measuring the Contact Pressure Between a Capsule and the Small Intestine","type":"article-journal","volume":"139"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1109/ROBOT.2005.1570298","ISBN":"0-7803-8914-X","author":[{"dropping-particle":"","family":"Youngin Kim","given":"","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Geunho Lee","given":"","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sukho Park","given":"","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Byungkyu Kim","given":"","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jong-Oh Park","given":"","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jin-ho Cho","given":"","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Proceedings of the 2005 IEEE International Conference on Robotics and Automation","id":"ITEM-2","issue":"2","issued":{"date-parts":[["2005"]]},"page":"1321-1326","publisher":"IEEE","title":"Pressure Monitoring System in Gastro-Intestinal Tract","type":"paper-conference"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>123,124</sup>","plainTextFormattedCitation":"123,124","previouslyFormattedCitation":"<sup>124,125</sup>"},"properties":{"noteIndex":0},"schema":""}123,124. Despite these limitations, improved patient acceptance of IMCs in comparison to conventional manometryADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"ISBN":"7349367392","ISSN":"15547914","PMID":"22347818","abstract":"The wireless motility/pH capsule (WMC) is an orally ingested, nondigestible, data recording device that enables the simultaneous assessment of regional and whole gut transit. Approved by the US Food and Drug Administration for the evaluation of patients with suspected delayed gastric emptying and the evaluation of colonic transit time in patients with chronic idiopathic constipation, this capsule continuously measures the temperature, pH, and pressure of its surrounding environment while traveling through the gastrointestinal tract (via gut peristalsis) until exiting the body through the anus. Validated patterns in pH and temperature recordings allow for accurate measurement of gastric emptying, small bowel transit, colonic transit, and whole gut transit times. The WMC is a nonradioactive, office-based, gastrointestinal transit testing modality shown in several clinical trials to be a suitable alternative to scintigraphy and radiopaque marker studies in measuring gastric emptying, small bowel, colonic, and whole gut transit times. Unlike widely available transit tests, which provide only region-specific transit data, the WMC offers the benefit of measuring gastric, small bowel, and colonic transit times in a single examination. The WMC also provides intraluminal pressure readings throughout the digestive tract, offering a noninvasive means by which to assess gastrointestinal motility. The WMC should be considered the transit study of choice for individuals suspected of having altered transit in more than one region of the gastrointestinal tract. This review summarizes the features and performance characteristics of the WMC as well as provides a summary on how this diagnostic modality is most effectively used in the assessment of gastrointestinal symptom complexes due to suspected abnormalities in transit.","author":[{"dropping-particle":"","family":"Saad","given":"Richard J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hasler","given":"William L.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastroenterology and Hepatology","id":"ITEM-1","issue":"12","issued":{"date-parts":[["2011"]]},"page":"795-804","title":"A technical review and clinical assessment of the wireless motility capsule","type":"bill","volume":"7"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>116</sup>","plainTextFormattedCitation":"116","previouslyFormattedCitation":"<sup>116</sup>"},"properties":{"noteIndex":0},"schema":""}116 and the non-invasive potential of the IMC to capture multiregional GI dysmotility is advantageous in comparison to other methods. However, further work is required before these devices can provide information comparable to conventional manometry. [H3] Electrophysiology Gastrointestinal motility involves complex behavior governed by hormonal, myogenic and neurogenic factors that act together to mix and propel material along the gastrointestinal tract. In the small intestine, slow waves generated by the interstitial cells of Cajal (ICC) cause smooth muscle cells lining the intestine to polarize and depolarize, leading to contraction and relaxation respectively. Determining the pathophysiological role of these cells in dysmotility has attracted substantial research interestADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1152/physiol.00022.2013","ISBN":"1548-9213, 1548-9221","ISSN":"1548-9221","PMID":"23997190","abstract":"A key discovery in gastrointestinal motility has been the central role played by interstitial cells of Cajal (ICC) in generating electrical slow waves that coordinate contractions. Multielectrode mapping and multiscale modeling are two emerging interdisciplinary strategies now showing translational promise to investigate ICC function, electrophysiology, and contractions in the human gut.","author":[{"dropping-particle":"","family":"Cheng","given":"L. K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Du","given":"P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"O'Grady","given":"G.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Physiology (Bethesda, Md.)","id":"ITEM-1","issue":"5","issued":{"date-parts":[["2013","9"]]},"page":"310-7","title":"Mapping and modeling gastrointestinal bioelectricity: from engineering bench to bedside","type":"article-journal","volume":"28"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>125</sup>","plainTextFormattedCitation":"125","previouslyFormattedCitation":"<sup>126</sup>"},"properties":{"noteIndex":0},"schema":""}125. Several methods have been used to investigate the electrophysiology of the gastrointestinal tract in clinical settings. One approach is the non-invasive transcutaneous measurement of the myoelectric activity of the small bowel via electrogastroenterography (EEnG). However, transcutaneous EEnG suffers from several problems, such as interference between EEnG and cardiorespiratory signals and low EEnG signal amplitudeADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.3748/wjg.v23.i25.4517","ISBN":"1403220530","ISSN":"22192840","PMID":"28740340","abstract":"AIM To enhance the clinical utility of electrogastrography (EGG), which has been recorded since 1922, but is clinically unutilized. METHODS An innovative method to salvage the promise of EGG is proposed by introducing a preliminary procedure, while maintaining the electrodes, standardized equipment, and signal processing utilized in the well-established EGG testing of today. The proposed enhanced EGG (EEGG) protocol involves swallowing an ingestible capsule containing miniature electronic oscillator embedded in an expandable, self-disintegratable, biocompatible pseudobesoar residing in the stomach for the duration of the test. The benefits of the proposed approach are outlined, tested and discussed in details. RESULTS Experiments were performed on eight mongrel dogs (6F, 4M, 23.8 ± 3.3 kg). Four were administered an active EEGG capsule, while the rest were given a deactivated (battery removed) capsule. Pharmacologically facilitated gastric motility revealed a significant (P < 0.01) Pearson correlation between gastric motility indices obtained by force transducers implanted directly on the stomach, and the motility indices obtained by EEGG. A particular emphasis was made on preserving standard EGG-related hardware and software in order to facilitate the introduction of the proposed EEGG in environments which already utilize standard EGG testing. The expanded intragastric pseudobezoar containing the miniature electronic oscillator was retained during the tests, and could be disintegrated on demand. CONCLUSION Enhancing standard EGG by an ingestible, self-expanding and self-disintegrating pseudobesoar containing a miniature electronic oscillator can be an important avenue for clinical applicability of this test.","author":[{"dropping-particle":"","family":"Poscente","given":"Michael D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mintchev","given":"Martin P.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"World Journal of Gastroenterology","id":"ITEM-1","issue":"25","issued":{"date-parts":[["2017"]]},"page":"4517-4528","title":"Enhanced electrogastrography: A realistic way to salvage a promise that was never kept?","type":"article-journal","volume":"23"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>126</sup>","plainTextFormattedCitation":"126","previouslyFormattedCitation":"<sup>127</sup>"},"properties":{"noteIndex":0},"schema":""}126. The relationship between clinical presentation and EEnG data is weak, which hinders clinical acceptanceADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.3748/wjg.v23.i25.4517","ISBN":"1403220530","ISSN":"22192840","PMID":"28740340","abstract":"AIM To enhance the clinical utility of electrogastrography (EGG), which has been recorded since 1922, but is clinically unutilized. METHODS An innovative method to salvage the promise of EGG is proposed by introducing a preliminary procedure, while maintaining the electrodes, standardized equipment, and signal processing utilized in the well-established EGG testing of today. The proposed enhanced EGG (EEGG) protocol involves swallowing an ingestible capsule containing miniature electronic oscillator embedded in an expandable, self-disintegratable, biocompatible pseudobesoar residing in the stomach for the duration of the test. The benefits of the proposed approach are outlined, tested and discussed in details. RESULTS Experiments were performed on eight mongrel dogs (6F, 4M, 23.8 ± 3.3 kg). Four were administered an active EEGG capsule, while the rest were given a deactivated (battery removed) capsule. Pharmacologically facilitated gastric motility revealed a significant (P < 0.01) Pearson correlation between gastric motility indices obtained by force transducers implanted directly on the stomach, and the motility indices obtained by EEGG. A particular emphasis was made on preserving standard EGG-related hardware and software in order to facilitate the introduction of the proposed EEGG in environments which already utilize standard EGG testing. The expanded intragastric pseudobezoar containing the miniature electronic oscillator was retained during the tests, and could be disintegrated on demand. CONCLUSION Enhancing standard EGG by an ingestible, self-expanding and self-disintegrating pseudobesoar containing a miniature electronic oscillator can be an important avenue for clinical applicability of this test.","author":[{"dropping-particle":"","family":"Poscente","given":"Michael D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mintchev","given":"Martin P.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"World Journal of Gastroenterology","id":"ITEM-1","issue":"25","issued":{"date-parts":[["2017"]]},"page":"4517-4528","title":"Enhanced electrogastrography: A realistic way to salvage a promise that was never kept?","type":"article-journal","volume":"23"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>126</sup>","plainTextFormattedCitation":"126","previouslyFormattedCitation":"<sup>127</sup>"},"properties":{"noteIndex":0},"schema":""}126. One method to improve this involves the integration of EEnG within a wireless, ingestible capsule. Woo et al.ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1007/s11517-009-0567-4","ISSN":"0140-0118","PMID":"20039141","abstract":"A telemetry capsule system was designed and implemented to measure the slow wave activity of the small bowel, which is an important parameter for the diagnosis of gastric diseases. The capsule amplified the slow wave signal from the intraluminal electrodes, and transmitted the digitally sampled data by means of a radio frequency transmitter. The implemented capsule (11 x 21 mm(2)) was smaller than a commercially available capsule endoscope, and it can remain active for more than 18 h. The feasibility of using this capsule was investigated by conducting in vitro experiments, and the average motility signals of the ileum, jejunum, and colon were measured as 6.1, 10.2, and 1.5 cycles per minute, respectively","author":[{"dropping-particle":"","family":"Woo","given":"S H","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cho","given":"J H","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Medical & Biological Engineering & Computing","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2010","3","29"]]},"page":"277-283","title":"Telemetry system for slow wave measurement from the small bowel","type":"article-journal","volume":"48"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>127</sup>","plainTextFormattedCitation":"127","previouslyFormattedCitation":"<sup>128</sup>"},"properties":{"noteIndex":0},"schema":""}127 reported the design, construction and testing of a wireless CE capable of measuring the slow waves generated by ICC. This 11 mm diameter, 21 mm long capsule contained two surgical steel electrodes that contacted with the surrounding mucosa and detected the changing electrical potentials of the intestinal smooth muscles, before subsequent amplification and filtering. The system could operate for up to 18 hours with two coin-size batteries similar to those used in conventional capsule endoscopes. The capsule was tested ex vivo using two, freshly excised, samples of porcine intestine immersed in a modified Krebs solution. The results demonstrated successful detection of myoelectric activity within these tissue samples, but only at a fixed point due toowing to frictional forces. The two electrodes limited the radial resolution of any electrophysiological mapping of the small intestine but, owing to the passage of the capsule through the intestine, the longitudinal resolution was limited only by the distance between the electrodes. No further results from this research have been provided have been published since 2010, though the authors have adapted some of this technology as a means of electrical propulsion of a CE through the GI tractADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1186/1475-925X-10-108","ISSN":"1475-925X","PMID":"22177218","abstract":"The aim of this research is to propose a small intestine model for electrically propelled capsule endoscopy. The electrical stimulus can cause contraction of the small intestine and propel the capsule along the lumen. The proposed model considered the drag and friction from the small intestine using a thin walled model and Stokes' drag equation. Further, contraction force from the small intestine was modeled by using regression analysis. From the proposed model, the acceleration and velocity of various exterior shapes of capsule were calculated, and two exterior shapes of capsules were proposed based on the internal volume of the capsules. The proposed capsules were fabricated and animal experiments were conducted. One of the proposed capsules showed an average (SD) velocity in forward direction of 2.91 ± 0.99 mm/s and 2.23 ± 0.78 mm/s in the backward direction, which was 5.2 times faster than that obtained in previous research. The proposed model can predict locomotion of the capsule based on various exterior shapes of the capsule.","author":[{"dropping-particle":"","family":"Woo","given":"Sang Hyo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kim","given":"Tae Wan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mohy-Ud-Din","given":"Zia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Park","given":"Il Young","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cho","given":"Jin-ho","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Biomedical engineering online","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2011"]]},"page":"108","publisher":"BioMed Central Ltd","title":"Small intestinal model for electrically propelled capsule endoscopy.","type":"article-journal","volume":"10"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>128</sup>","plainTextFormattedCitation":"128","previouslyFormattedCitation":"<sup>129</sup>"},"properties":{"noteIndex":0},"schema":""}128. [H2]Biochemical Measurements Gastrointestinal disease can be associated with a change in the biochemical profile of luminal contents; for example, levels of fecal calprotectin are elevated in patients with IBD. CE offers a unique opportunity to perform minimally invasive screening in situ, which could enable monitoring of gastrointestinal disease progression when coupled with improved capsule localization methods. Capsules capable of measuring pH, hemoglobin and changes in microbiome metabolic byproducts have been developed in several studies, with varying degrees of success. [H3]pH The pH of a healthy gastrointestinal tract varies with location, time since ingestion, age and dietADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1002/jps.21502","ISSN":"00223549","author":[{"dropping-particle":"","family":"Clarysse","given":"S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tack","given":"J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lammert","given":"F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Duchateau","given":"G.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Reppas","given":"C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Augustijns","given":"P.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Pharmaceutical Sciences","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2009","3"]]},"page":"1177-1192","publisher":"Wiley Subscription Services, Inc., A Wiley Company","title":"Postprandial Evolution in Composition and Characteristics of Human Duodenal Fluids in Different Nutritional States","type":"article-journal","volume":"98"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1002/jps.24696","ISSN":"15206017","PMID":"26539698","abstract":"Oral bioavailability studies during the development of new medical entities or generic drugs are typically performed in healthy volunteers. Approved drug products are, however, used by patients with diverse disease backgrounds, and by pediatric and elderly patients. To provide the knowledge base for assessing the potential effects of age or co-morbidity on the in vivo performance of an orally absorbed, systemically active drug product, the literature regarding the gastrointestinal (GI) physiological characteristics (pH, permeability, and transit time) in children, in the elderly, and in patients with GI diseases (irritable bowel syndrome, ulcerative colitis, and Crohn's disease) is reviewed herein, with the knowledge gaps highlighted.","author":[{"dropping-particle":"","family":"Bai","given":"Jane P F","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Burckart","given":"Gilbert J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mulberg","given":"Andrew E.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Pharmaceutical Sciences","id":"ITEM-2","issue":"2","issued":{"date-parts":[["2016","2"]]},"page":"476-483","title":"Literature Review of Gastrointestinal Physiology in the Elderly, in Pediatric Patients, and in Patients with Gastrointestinal Diseases","type":"article-journal","volume":"105"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>129,130</sup>","plainTextFormattedCitation":"129,130","previouslyFormattedCitation":"<sup>130,131</sup>"},"properties":{"noteIndex":0},"schema":""}129,130. Changes in pH are often used in the diagnosis of gastroesophagealoesophageal reflux disease (GERD)ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1007/s13304-018-0563-z","ISSN":"2038-131X","author":[{"dropping-particle":"","family":"Fisichella","given":"Piero Marco","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schlottmann","given":"Francisco","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Patti","given":"Marco G.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Updates in Surgery","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2018","9","23"]]},"page":"309-313","title":"Evaluation of gastroesophageal reflux disease","type":"article-journal","volume":"70"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>131</sup>","plainTextFormattedCitation":"131","previouslyFormattedCitation":"<sup>132</sup>"},"properties":{"noteIndex":0},"schema":""}131 and the measurement of GI transit time through the use of CEs with suitable sensors. However, other studies have sought to demonstrate the potential of changes in pH as a marker of other GI diseases with mixed results ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1007/BF01297074","ISSN":"0163-2116","author":[{"dropping-particle":"","family":"Fallingborg","given":"Jan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Christensen","given":"Lisbet Ambrosius","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jacobsen","given":"Bent Ascanius","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rasmussen","given":"Sten N?rby","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Digestive Diseases and Sciences","id":"ITEM-1","issue":"11","issued":{"date-parts":[["1993","11"]]},"page":"1989-1993","publisher":"Kluwer Academic Publishers-Plenum Publishers","title":"Very low intraluminal colonic pH in patients with active ulcerative colitis","type":"article-journal","volume":"38"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1016/S0016-5085(00)85265-8","ISSN":"00165085","author":[{"dropping-particle":"","family":"Nugent","given":"SG","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kumar","given":"D","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rampton","given":"DS","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yazaki","given":"E","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Evans","given":"DF","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gut","id":"ITEM-2","issue":"A9","issued":{"date-parts":[["2000"]]},"page":"A781","publisher":"American Gastroenterological Association","title":"Gut pH and transit time in ulcerative colitis appear sufficient for complete dissolution of pH-dependent mesalazine-containing capsules.","type":"article-journal","volume":"46"},"uris":[""]},{"id":"ITEM-3","itemData":{"ISSN":"0269-2813","PMID":"9701532","abstract":"5-Amino salicylic acid preparations are used in therapy for patients with inflammatory bowel diseases. The bioavailability of these drugs depends on their coating.","author":[{"dropping-particle":"","family":"Press","given":"A.G. G","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hauptmann","given":"I.A. A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hauptmann","given":"L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fuchs","given":"B.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fuchs","given":"M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ewe","given":"K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ramadori","given":"G","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Alimentary pharmacology & therapeutics","id":"ITEM-3","issue":"7","issued":{"date-parts":[["1998","7"]]},"page":"673-8","title":"Gastrointestinal pH profiles in patients with inflammatory bowel disease.","type":"article-journal","volume":"12"},"uris":[""]},{"id":"ITEM-4","itemData":{"DOI":"10.1023/A:1018893409596","ISBN":"0163-2116 (Print)\\r0163-2116","ISSN":"01632116","PMID":"9558022","abstract":"The pH and transit times of the gut are important for the delivery of active drug from several tablets used in the treatment of Crohn's disease (CD). Many patients with CD undergo an ileocecal resection, which might influence small intestinal pH and transit time. The effect of ileocecal resection on these variables has not previously been studied. Intraluminal pH and transit time were measured in nine ileocecal-resected CD patients and 13 healthy volunteers using pH-sensitive radiocapsules. Small intestinal transit time (SITT) was significantly shorter in ileocecal-resected patients (5.2 hr, controls 8.0 hr). The pH levels of the small intestine were identical in patients and controls, whereas cecal pH was 0.9 pH units higher in resected CD patients. The time spent with pH higher than 5.5, 6.0, 6.5, and 7.0 was significantly shorter in patients than in controls. There was no correlation between the SITT and the length of resected ileum or between the SITT and the time elapsed since the resection. We conclude that ileocecal resection decreases the SITT and the time with pH higher than 5.5-7.0. The study indicates that this reduction of the SITT is mainly due to the resection of the ileocecal valve and is, to a certain extent, independent of the length of resected ileum. An ileocecal resection might therefore affect the delivery of active drug from tablets with pH-dependent delivery.","author":[{"dropping-particle":"","family":"Fallingborg","given":"Jan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pedersen","given":"Poul","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jacobsen","given":"Bent A.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Digestive Diseases and Sciences","id":"ITEM-4","issue":"4","issued":{"date-parts":[["1998"]]},"page":"702-705","title":"Small intestinal transit time and intraluminal pH in ileocecal resected patients with Crohn's disease","type":"article-journal","volume":"43"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>132–135</sup>","plainTextFormattedCitation":"132–135","previouslyFormattedCitation":"<sup>133–136</sup>"},"properties":{"noteIndex":0},"schema":""}132–135. These earlierEarlier studies used a battery-powered, wireless ingestible pH telemetry capsule with an onboard transducer comprising two reference electrodes, the output of which is sent to an external data logger via an integrated radiofrequency transmitterADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"ISSN":"0378-309X","PMID":"7337824","abstract":"The design of a new radiotelemetry capsule (26 mm long X 7.6 mm diameter), with an in vivo life of 1 month is described in the context of previous work in this field. In vitro evaluation of the capsule indicates an accuracy and performance comparable with a conventional pH meter. Several clinical applications are described, including measurements of gastrointestinal pH in humans and the measurement of extracellular pH in laboratory animals.","author":[{"dropping-particle":"","family":"Colson","given":"R H","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Watson","given":"B W","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fairclough","given":"P D","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Walker-Smith","given":"J A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Campbell","given":"C A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bellamy","given":"D","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hinsull","given":"S M","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Biotelemetry and patient monitoring","id":"ITEM-1","issue":"4","issued":{"date-parts":[["1981"]]},"page":"213-27","title":"An accurate, long-term, pH-sensitive radio pill for ingestion and implantation.","type":"article-journal","volume":"8"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>136</sup>","plainTextFormattedCitation":"136","previouslyFormattedCitation":"<sup>137</sup>"},"properties":{"noteIndex":0},"schema":""}136. AltThough these capsules were reported to have difficulty withexperience up to 75% signal loss caused by poor alignment between the transmitting and receiving aerials they were considered an improvement over other methods previously used in vivo. Some studies have demonstrated that ulcerative colitis can cause a decrease in pH within the right colonADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1007/BF01297074","ISSN":"0163-2116","author":[{"dropping-particle":"","family":"Fallingborg","given":"Jan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Christensen","given":"Lisbet Ambrosius","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jacobsen","given":"Bent Ascanius","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rasmussen","given":"Sten N?rby","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Digestive Diseases and Sciences","id":"ITEM-1","issue":"11","issued":{"date-parts":[["1993","11"]]},"page":"1989-1993","publisher":"Kluwer Academic Publishers-Plenum Publishers","title":"Very low intraluminal colonic pH in patients with active ulcerative colitis","type":"article-journal","volume":"38"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1016/S0016-5085(00)85265-8","ISSN":"00165085","author":[{"dropping-particle":"","family":"Nugent","given":"SG","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kumar","given":"D","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rampton","given":"DS","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yazaki","given":"E","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Evans","given":"DF","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gut","id":"ITEM-2","issue":"A9","issued":{"date-parts":[["2000"]]},"page":"A781","publisher":"American Gastroenterological Association","title":"Gut pH and transit time in ulcerative colitis appear sufficient for complete dissolution of pH-dependent mesalazine-containing capsules.","type":"article-journal","volume":"46"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>132,133</sup>","plainTextFormattedCitation":"132,133","previouslyFormattedCitation":"<sup>133,134</sup>"},"properties":{"noteIndex":0},"schema":""}132,133, whereas results for other IBDs such as Crohn’s disease have been contradictoryADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"ISSN":"0269-2813","PMID":"9701532","abstract":"5-Amino salicylic acid preparations are used in therapy for patients with inflammatory bowel diseases. The bioavailability of these drugs depends on their coating.","author":[{"dropping-particle":"","family":"Press","given":"A.G. G","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hauptmann","given":"I.A. A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hauptmann","given":"L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fuchs","given":"B.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fuchs","given":"M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ewe","given":"K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ramadori","given":"G","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Alimentary pharmacology & therapeutics","id":"ITEM-1","issue":"7","issued":{"date-parts":[["1998","7"]]},"page":"673-8","title":"Gastrointestinal pH profiles in patients with inflammatory bowel disease.","type":"article-journal","volume":"12"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>134</sup>","plainTextFormattedCitation":"134","previouslyFormattedCitation":"<sup>135</sup>"},"properties":{"noteIndex":0},"schema":""}134,ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1023/A:1018893409596","ISBN":"0163-2116 (Print)\\r0163-2116","ISSN":"01632116","PMID":"9558022","abstract":"The pH and transit times of the gut are important for the delivery of active drug from several tablets used in the treatment of Crohn's disease (CD). Many patients with CD undergo an ileocecal resection, which might influence small intestinal pH and transit time. The effect of ileocecal resection on these variables has not previously been studied. Intraluminal pH and transit time were measured in nine ileocecal-resected CD patients and 13 healthy volunteers using pH-sensitive radiocapsules. Small intestinal transit time (SITT) was significantly shorter in ileocecal-resected patients (5.2 hr, controls 8.0 hr). The pH levels of the small intestine were identical in patients and controls, whereas cecal pH was 0.9 pH units higher in resected CD patients. The time spent with pH higher than 5.5, 6.0, 6.5, and 7.0 was significantly shorter in patients than in controls. There was no correlation between the SITT and the length of resected ileum or between the SITT and the time elapsed since the resection. We conclude that ileocecal resection decreases the SITT and the time with pH higher than 5.5-7.0. The study indicates that this reduction of the SITT is mainly due to the resection of the ileocecal valve and is, to a certain extent, independent of the length of resected ileum. An ileocecal resection might therefore affect the delivery of active drug from tablets with pH-dependent delivery.","author":[{"dropping-particle":"","family":"Fallingborg","given":"Jan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pedersen","given":"Poul","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jacobsen","given":"Bent A.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Digestive Diseases and Sciences","id":"ITEM-1","issue":"4","issued":{"date-parts":[["1998"]]},"page":"702-705","title":"Small intestinal transit time and intraluminal pH in ileocecal resected patients with Crohn's disease","type":"article-journal","volume":"43"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>135</sup>","plainTextFormattedCitation":"135","previouslyFormattedCitation":"<sup>136</sup>"},"properties":{"noteIndex":0},"schema":""}135. Fallingborg et al. found that three of six patients with ulcerative colitis had a proximal colon pH of 2.3 to 3.4ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1007/BF01297074","ISSN":"0163-2116","author":[{"dropping-particle":"","family":"Fallingborg","given":"Jan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Christensen","given":"Lisbet Ambrosius","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jacobsen","given":"Bent Ascanius","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rasmussen","given":"Sten N?rby","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Digestive Diseases and Sciences","id":"ITEM-1","issue":"11","issued":{"date-parts":[["1993","11"]]},"page":"1989-1993","publisher":"Kluwer Academic Publishers-Plenum Publishers","title":"Very low intraluminal colonic pH in patients with active ulcerative colitis","type":"article-journal","volume":"38"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>132</sup>","plainTextFormattedCitation":"132","previouslyFormattedCitation":"<sup>133</sup>"},"properties":{"noteIndex":0},"schema":""}132. The other three patients had normal luminal pH profiles of between 6.8 -to 7.4 at the proximal colon. In two other studies, Nugent et al. measured a reduction in colonic luminal pH to <5.5 in two of six patients with ulcerative colitis when compared with healthy controls ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/S0016-5085(00)85265-8","ISSN":"00165085","author":[{"dropping-particle":"","family":"Nugent","given":"SG","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kumar","given":"D","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rampton","given":"DS","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yazaki","given":"E","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Evans","given":"DF","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gut","id":"ITEM-1","issue":"A9","issued":{"date-parts":[["2000"]]},"page":"A781","publisher":"American Gastroenterological Association","title":"Gut pH and transit time in ulcerative colitis appear sufficient for complete dissolution of pH-dependent mesalazine-containing capsules.","type":"article-journal","volume":"46"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>133</sup>","plainTextFormattedCitation":"133","previouslyFormattedCitation":"<sup>134</sup>"},"properties":{"noteIndex":0},"schema":""}133 and Press et al. observed a slight increase in the higher right colonic luminal pH in eleven 11 patients with ulcerative colitis compared with healthy control individualsADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"ISSN":"0269-2813","PMID":"9701532","abstract":"5-Amino salicylic acid preparations are used in therapy for patients with inflammatory bowel diseases. The bioavailability of these drugs depends on their coating.","author":[{"dropping-particle":"","family":"Press","given":"A.G. G","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hauptmann","given":"I.A. A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hauptmann","given":"L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fuchs","given":"B.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fuchs","given":"M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ewe","given":"K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ramadori","given":"G","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Alimentary pharmacology & therapeutics","id":"ITEM-1","issue":"7","issued":{"date-parts":[["1998","7"]]},"page":"673-8","title":"Gastrointestinal pH profiles in patients with inflammatory bowel disease.","type":"article-journal","volume":"12"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>134</sup>","plainTextFormattedCitation":"134","previouslyFormattedCitation":"<sup>135</sup>"},"properties":{"noteIndex":0},"schema":""}134. Owing to the limited sample sizes, further work is needed to verify these studies and demonstrate whether pH can act as a realistic and specific biomarker for IBD or IBD severity.Since the development of these initial capsules, three other devices capable of detecting changes in luminal pH have become available commercially. The wireless BRAVO capsule (Medtronic, Yoqneam, Israel) is a 26mm x 6.3mm device that is designed primarily to detect gastroesophagealoesophageal reflux disease (GERD) by sensing and recording esophagealoesophageal pH for up to 96 hoursADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1097/01.mpg.0000177312.81071.c8","ISSN":"0277-2116","author":[{"dropping-particle":"","family":"Hochman","given":"Jay A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Favaloro-Sabatier","given":"Jennifer","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Pediatric Gastroenterology and Nutrition","id":"ITEM-1","issue":"4","issued":{"date-parts":[["2005","10"]]},"page":"411-415","title":"Tolerance and Reliability of Wireless pH Monitoring in Children","type":"article-journal","volume":"41"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>137</sup>","plainTextFormattedCitation":"137","previouslyFormattedCitation":"<sup>138</sup>"},"properties":{"noteIndex":0},"schema":""}137. The wireless Intellicap capsule (Philips, Eindhoven, Netherlands) is an 11 mm diameter, 27?mm long capsule for targeted drug delivery that uses its pH sensor to determine when to empty the contents of its drug reservoir into a specific region in the gastrointestinal tract. Initial tests conducted on 10 human volunteers with the Intellicap showed that using the pH profile for capsule localization agreed with the position determined with scintigraphy in all volunteersADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.gie.2013.03.170","ISBN":"0016-5107","ISSN":"00165107","PMID":"23684148","abstract":"Background: We developed an ingestible electronic drug delivery and monitoring system. This system includes an electronic capsule comprising a drug reservoir, a pH and temperature sensor, a microprocessor and wireless transceiver, a stepper motor, and batteries. The location of the capsule in the gut derived from pH data can be monitored in real time. The stepper motor can be remotely actuated to expel the contents of the drug reservoir. Objectives: First human study. Design: Two consecutive observational studies. Setting: University medical center. Subjects: Twenty healthy volunteers. Interventions: Study I: Ingestion and passage of the capsule. Study II: Ingestion and passage of the capsule, loaded with99mtechnetium-pertechnetate (99mTc); remotely actuated expulsion of99mTc in the gut. Main Outcome Measurements: Study I: Safety, tolerability, and functionality (wireless pH and temperature recording). Study II: Tracing of the capsule and expulsion and distribution of99mTc from the drug reservoir by scintigraphy. Correlating location pH with scintigraphy. Results: Study I: Ingestion and passage of the capsule was safe and well tolerated. Transmitted pH and temperature data were received by the recorder in 96.5% ± 3%. Study II: pH-determined passage of the esophagogastric, gastroduodenal, and ileocolonic junction correlated well with scintigraphy. Expulsion of99mTc from the capsule was successful in 9 of 10 subjects. Limitations: Subjects with relatively low body mass index. Conclusions: This electronic drug delivery and monitoring system may be a promising tool for targeted delivery of substances to well-defined areas of the GI tract. Copyright ? 2013 by the American Society for Gastrointestinal Endoscopy.","author":[{"dropping-particle":"","family":"Schaar","given":"Peter J.","non-dropping-particle":"Van Der","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dijksman","given":"J. Frits","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Broekhuizen-De Gast","given":"Henny","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shimizu","given":"Jeff","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lelyveld","given":"Niels","non-dropping-particle":"Van","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zou","given":"Hans","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Iordanov","given":"Ventzeslav","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wanke","given":"Christoph","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Siersema","given":"Peter D.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastrointestinal Endoscopy","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2013"]]},"page":"520-528","publisher":"Elsevier Ltd","title":"A novel ingestible electronic drug delivery and monitoring device","type":"article-journal","volume":"78"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>138</sup>","plainTextFormattedCitation":"138","previouslyFormattedCitation":"<sup>139</sup>"},"properties":{"noteIndex":0},"schema":""}138. This capsule has been assessed primarily for therapeutic deliveryADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.jconrel.2015.09.024","ISSN":"01683659","author":[{"dropping-particle":"","family":"S?derlind","given":"Erik","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Abrahamsson","given":"Bertil","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Erlandsson","given":"Fredrik","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wanke","given":"Christoph","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Iordanov","given":"Ventzeslav","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Corswant","given":"Christian","non-dropping-particle":"von","parse-names":false,"suffix":""}],"container-title":"Journal of Controlled Release","id":"ITEM-1","issued":{"date-parts":[["2015","11"]]},"page":"300-307","title":"Validation of the IntelliCap? system as a tool to evaluate extended release profiles in human GI tract using metoprolol as model drug","type":"article-journal","volume":"217"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1002/jps.24274","ISSN":"00223549","author":[{"dropping-particle":"","family":"Koziolek","given":"Mirko","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Grimm","given":"Michael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Becker","given":"Dieter","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Iordanov","given":"Ventzeslav","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zou","given":"Hans","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shimizu","given":"Jeff","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wanke","given":"Christoph","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Garbacz","given":"Grzegorz","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Weitschies","given":"Werner","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Pharmaceutical Sciences","id":"ITEM-2","issue":"9","issued":{"date-parts":[["2015","9"]]},"page":"2855-2863","title":"Investigation of pH and Temperature Profiles in the GI Tract of Fasted Human Subjects Using the Intellicap? System","type":"article-journal","volume":"104"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1371/journal.pone.0129076","ISBN":"1932-6203","ISSN":"1932-6203","PMID":"26177019","abstract":"INTRODUCTION: ColoPulse tablets are an innovative development in the field of oral dosage forms characterized by a distal ileum and colon-specific release. Previous studies in humans showed release in the ileo-colonic region, but the relationship between gastrointestinal pH and release was not experimentally proven in vivo. This information will complete the in vivo release-profile of ColoPulse tablets.\\n\\nMATERIALS AND METHODS: Release from ColoPulse tablets was studied in 16 healthy volunteers using the dual label isotope strategy. To determine gastrointestinal pH profiles and transit times the IntelliCap system was used. A ColoPulse tablet containing 13C-urea and an uncoated, immediate release tablet containing 15N2-urea were taken simultaneously followed by a standardized breakfast after three hours. Five minutes after intake of the tablets the IntelliCap capsule was swallowed and pH was measured until excretion in the feces. Breath and urine samples were collected for isotope analysis.\\n\\nRESULTS: Full analysis could be performed in 12 subjects. Median bioavailability of 13C -urea was 82% (95% CI 74-94%, range 61-114%). The median lag time (5% release of 13C) was 5:42 h (95% CI 5:18-6:18 h, range 2:36-6:36 h,) There was no statistically significant difference between lag time based on isotope signal and colon arrival time (CAT) based on pH (median 5:42 vs 5:31 h p = 0.903). In all subjects an intestinal pH value of 7.0 was reached before release of 13C from the ColoPulse tablet occurred.\\n\\nDISCUSSION AND CONCLUSIONS: From the combined data from the IntelliCap system and the 13C -isotope signal it can be concluded that release from a ColoPulse tablet in vivo is not related to transit times but occurs in the ileo-colonic region after pH 7.0 is reached. This supports our earlier findings and confirms that the ColoPulse system is a promising delivery system for targeting the distal ileum and colon.\\n\\nTRIAL REGISTRATION: ISRCTN Registry 18301880.","author":[{"dropping-particle":"","family":"Maurer","given":"Jacoba M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schellekens","given":"Reinout C. A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rieke","given":"Hèlen M.","non-dropping-particle":"van","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wanke","given":"Christoph","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Iordanov","given":"Ventzeslav","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stellaard","given":"Frans","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wutzke","given":"Klaus D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dijkstra","given":"Gerard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zee","given":"Margot","non-dropping-particle":"van der","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Woerdenbag","given":"Herman J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Frijlink","given":"Henderik W.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kosterink","given":"Jos G. W.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"PLOS ONE","editor":[{"dropping-particle":"","family":"Padmanabhan","given":"Parasuraman","non-dropping-particle":"","parse-names":false,"suffix":""}],"id":"ITEM-3","issue":"7","issued":{"date-parts":[["2015","7","15"]]},"page":"e0129076","title":"Gastrointestinal pH and Transit Time Profiling in Healthy Volunteers Using the IntelliCap System Confirms Ileo-Colonic Release of ColoPulse Tablets","type":"article-journal","volume":"10"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>139–141</sup>","plainTextFormattedCitation":"139–141","previouslyFormattedCitation":"<sup>140–142</sup>"},"properties":{"noteIndex":0},"schema":""}139–141. SmartPill is approvedADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"ISBN":"7349367392","ISSN":"15547914","PMID":"22347818","abstract":"The wireless motility/pH capsule (WMC) is an orally ingested, nondigestible, data recording device that enables the simultaneous assessment of regional and whole gut transit. Approved by the US Food and Drug Administration for the evaluation of patients with suspected delayed gastric emptying and the evaluation of colonic transit time in patients with chronic idiopathic constipation, this capsule continuously measures the temperature, pH, and pressure of its surrounding environment while traveling through the gastrointestinal tract (via gut peristalsis) until exiting the body through the anus. Validated patterns in pH and temperature recordings allow for accurate measurement of gastric emptying, small bowel transit, colonic transit, and whole gut transit times. The WMC is a nonradioactive, office-based, gastrointestinal transit testing modality shown in several clinical trials to be a suitable alternative to scintigraphy and radiopaque marker studies in measuring gastric emptying, small bowel, colonic, and whole gut transit times. Unlike widely available transit tests, which provide only region-specific transit data, the WMC offers the benefit of measuring gastric, small bowel, and colonic transit times in a single examination. The WMC also provides intraluminal pressure readings throughout the digestive tract, offering a noninvasive means by which to assess gastrointestinal motility. The WMC should be considered the transit study of choice for individuals suspected of having altered transit in more than one region of the gastrointestinal tract. This review summarizes the features and performance characteristics of the WMC as well as provides a summary on how this diagnostic modality is most effectively used in the assessment of gastrointestinal symptom complexes due to suspected abnormalities in transit.","author":[{"dropping-particle":"","family":"Saad","given":"Richard J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hasler","given":"William L.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastroenterology and Hepatology","id":"ITEM-1","issue":"12","issued":{"date-parts":[["2011"]]},"page":"795-804","title":"A technical review and clinical assessment of the wireless motility capsule","type":"bill","volume":"7"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>116</sup>","plainTextFormattedCitation":"116","previouslyFormattedCitation":"<sup>116</sup>"},"properties":{"noteIndex":0},"schema":""}116 to investigate gastrointestinal motility via integrated pH, pressure and temperature sensors that are previously described. The temperature and pressure sensing capabilities of this device have been previously discussed. The battery life of the capsule is specified to be up to 5 days, enabling data transmission throughout the entire gastrointestinal tract until excretion. Such a long battery life is achieved partly by adjusting the sampling rates of the sensors after 24 hADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1007/s10620-009-0899-9","ISSN":"0163-2116","abstract":"INTRODUCTION: Assessment of whole gut transit, by radio-opaque markers or scintigraphy, is used to evaluate patients with constipation for slow gastrointestinal transit. Wireless capsule motility, using the SmartPill GI monitoring system, samples and transmits intraluminal pH, pressure, and temperature data from a capsule at regular intervals as it traverses through the gastrointestinal tract; from these, gastric emptying and whole gastrointestinal tract transit can be assessed. The objective of this study was to compare the SmartPill with whole gut transit scintigraphy to determine whether the SmartPill system could serve as a test for measurement of whole gut motility and transit. METHODS: Ten healthy, asymptomatic subjects underwent simultaneous whole gut scintigraphy and SmartPill assessment of whole gut transit. RESULTS: All subjects completed the study per protocol and experienced natural passage of the pill. Capsule residence time in the stomach correlated very strongly with percent gastric retention of the Tc-99 radiolabel at 120 min (r = 0.95) and at 240 min (r = 0.73). Small bowel contraction-min(-1) measured by the SmartPill correlated with small bowel transit % (r = 0.69; P = 0.05) and with isotopic colonic geometric center at 24 h after ingestion (r = 0.70, P = 0.024). Capsule transit time correlated with scintigraphic assessment of whole gut transit. CONCLUSIONS: SmartPill capsule assessment of gastric emptying and whole gut transit compares favorably with that of scintigraphy. Wireless capsule motility shows promise as a useful diagnostic test to evaluate patients for GI transit disorders and to study the effect of prokinetic agents on GI transit.","author":[{"dropping-particle":"","family":"Maqbool","given":"Sabba","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Parkman","given":"Henry P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Friedenberg","given":"Frank K.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Digestive Diseases and Sciences","id":"ITEM-1","issue":"10","issued":{"date-parts":[["2009","10","5"]]},"page":"2167-2174","title":"Wireless Capsule Motility: Comparison of the SmartPill? GI Monitoring System with Scintigraphy for Measuring Whole Gut Transit","type":"article-journal","volume":"54"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>142</sup>","plainTextFormattedCitation":"142","previouslyFormattedCitation":"<sup>143</sup>"},"properties":{"noteIndex":0},"schema":""}142. Protocols for measuring the transit time of the capsule from the rate of change of pH along the gastrointestinal tract have been definedADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"ISSN":"1542-7714","PMID":"19418602","abstract":"BACKGROUND & AIMS Colonic transit time (CTT) traditionally is assessed with radiopaque markers (ROMs), which requires radiation and is hindered by lack of standardization and compliance. We assessed regional and CTT with the SmartPill (SmartPill Corporation, Buffalo, NY), a new wireless pH and pressure recording capsule, in constipated and healthy subjects and compared this with ROM. METHODS Seventy-eight constipated (Rome II) and 87 healthy subjects ingested a 260-kcal meal, a ROM capsule, and the SmartPill. Subjects wore a data receiver and kept daily stool diaries for 5 days. SmartPill recordings assessed CTT, whole-gut transit time (WGTT), small-bowel transit time, and gastric emptying time. Abdominal radiographs on days 2 and 5 assessed ROM transit. Sensitivity/specificity and receiver operating characteristics (ROCs) of each technique and utility were compared. RESULTS Gastric emptying time, CTT, and WGTT were slower (P < .01) in constipated subjects than controls. CTT was slower in women than men (P = .02). Day 2 and day 5 ROM transits were slower (P < .001) in constipated subjects. Correlation of the SmartPill CTT with ROMs expelled on day 2/day 5 was r = 0.74/r = 0.69 in constipation, and r = 0.70/r = 0.40 in controls, respectively. The diagnostic accuracy of the SmartPill CTT to predict constipation from ROC was 0.73, with a specificity of 0.95. These were comparable with those of day 5 ROM (ROC, 0.71; specificity, 0.95). CONCLUSIONS The SmartPill is a novel ambulatory technique of assessing regional (gastric, small bowel, colonic) and WGTT without radiation. It reveals hitherto unrecognized gender differences and upper-gut dysfunction in constipation. It correlates well with ROM and offers a standardized method of discriminating normal from slow colonic transit.","author":[{"dropping-particle":"","family":"Rao","given":"Satish S C","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kuo","given":"Braden","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"McCallum","given":"Richard W","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chey","given":"William D","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"DiBaise","given":"John K","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hasler","given":"William L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Koch","given":"Kenneth L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lackner","given":"Jeffrey M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Miller","given":"Carrie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Saad","given":"Richard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Semler","given":"Jack R","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sitrin","given":"Michael D","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wilding","given":"Gregory E","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Parkman","given":"Henry P","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association","id":"ITEM-1","issue":"5","issued":{"date-parts":[["2009","5"]]},"page":"537-44","title":"Investigation of colonic and whole-gut transit with wireless motility capsule and radiopaque markers in constipation.","type":"article-journal","volume":"7"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>143</sup>","plainTextFormattedCitation":"143","previouslyFormattedCitation":"<sup>144</sup>"},"properties":{"noteIndex":0},"schema":""}143. Although gastrointestinal motility studies using CE to date have involved small sample sizes of less than< 100 participants and had difficulties in experimental design (particularly with respect to selection of participantsADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1586/17474124.2014.922869","ISBN":"1747-4124","ISSN":"1747-4124","PMID":"24881810","abstract":"Testing to define delayed gastric emptying is required to diagnose gastroparesis; rapid emptying is found in other patients. Commonly performed methods of gastric emptying testing include scintigraphy and breath testing. The SmartPill wireless motility capsule (WMC) system is US FDA-approved for evaluating suspected delayed emptying in gastroparesis and functional dyspepsia. The device measures transit in the stomach, small intestine, and colon by detecting characteristic pH transitions; and quantifies pressure waves in each gut region. WMC gastric emptying times correlate with scintigraphic measures. Incremental benefits of WMC testing in patients with suspected gastroparesis include delineation of pressure abnormalities and small intestinal and colonic transit delays. Acceptance of trial data confirming usefulness of WMC testing in suspected gastric motor disorders has been hampered by small sample sizes and design limitations. Ongoing multicenter studies will validate the utility of WMC methods in patients with suspected gastroparesis and other upper gastrointestinal motor disorders.","author":[{"dropping-particle":"","family":"Hasler","given":"William L","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Expert Review of Gastroenterology & Hepatology","id":"ITEM-1","issue":"6","issued":{"date-parts":[["2014","8","31"]]},"page":"587-600","title":"The use of SmartPill for gastric monitoring","type":"article-journal","volume":"8"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>144</sup>","plainTextFormattedCitation":"144","previouslyFormattedCitation":"<sup>145</sup>"},"properties":{"noteIndex":0},"schema":""}144), it has been suggested that the detection of gastric emptying time with CE devices such as SmartPill in patients with suspected gastroparesis has a sensitivity and specificity similar to that of gastric scintigraphyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/j.1365-2036.2007.03564.x","ISSN":"02692813","author":[{"dropping-particle":"","family":"KUO","given":"B.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"McCALLUM","given":"R. W.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"KOCH","given":"K. L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"SITRIN","given":"M. D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"WO","given":"J. M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"CHEY","given":"W. D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"HASLER","given":"W. L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"LACKNER","given":"J. M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"KATZ","given":"L. A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"SEMLER","given":"J. R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"WILDING","given":"G. E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"PARKMAN","given":"H. P.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Alimentary Pharmacology & Therapeutics","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2007","10","29"]]},"page":"186-196","title":"Comparison of gastric emptying of a nondigestible capsule to a radio-labelled meal in healthy and gastroparetic subjects","type":"article-journal","volume":"27"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>145</sup>","plainTextFormattedCitation":"145","previouslyFormattedCitation":"<sup>146</sup>"},"properties":{"noteIndex":0},"schema":""}145, which is commonly used to measure transit time across the length of the GI tract. A systematic review that compared the diagnostic capability of CE devices to gastric scintigraphy, antroduodenal manometry and endoscopy in the diagnostic accuracy of gastric emptying delay, motility assessment and treatment decisionsADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"PMID":"24049848","abstract":"The information in this report is intended to help health care decisionmakers—patients and clinicians, health system leaders, and policymakers, among others—make well informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients.","author":[{"dropping-particle":"","family":"Stein","given":"E","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Berger","given":"Z","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hutfless","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shah","given":"L","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Comparative Effectiveness Review","id":"ITEM-1","issue":"110","issued":{"date-parts":[["2013"]]},"title":"Wireless motility capsule versus other diagnostic technologies for evaluating gastroparesis and constipation: a comparative effectiveness review","type":"article-journal"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>115</sup>","plainTextFormattedCitation":"115","previouslyFormattedCitation":"<sup>115</sup>"},"properties":{"noteIndex":0},"schema":""}115 found, with a low strength of evidence, that SmartPill alone was comparable to gastric scintigraphy. A comparison of the diagnoses obtained with SmartPill and gastric scintigraphy showed an agreement of 59–86% for positive test results and 64–81% for negative test results. Overall agreement was in the range of 35–81%. The SmartPill offers a nonradioactive alternative to transit testing modalities, that can provide comparable measurements of gastric emptying time, small bowel transit time, colon transit time and whole gut transit time in a single device, reducing the need for separate regional testsADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"ISBN":"7349367392","ISSN":"15547914","PMID":"22347818","abstract":"The wireless motility/pH capsule (WMC) is an orally ingested, nondigestible, data recording device that enables the simultaneous assessment of regional and whole gut transit. Approved by the US Food and Drug Administration for the evaluation of patients with suspected delayed gastric emptying and the evaluation of colonic transit time in patients with chronic idiopathic constipation, this capsule continuously measures the temperature, pH, and pressure of its surrounding environment while traveling through the gastrointestinal tract (via gut peristalsis) until exiting the body through the anus. Validated patterns in pH and temperature recordings allow for accurate measurement of gastric emptying, small bowel transit, colonic transit, and whole gut transit times. The WMC is a nonradioactive, office-based, gastrointestinal transit testing modality shown in several clinical trials to be a suitable alternative to scintigraphy and radiopaque marker studies in measuring gastric emptying, small bowel, colonic, and whole gut transit times. Unlike widely available transit tests, which provide only region-specific transit data, the WMC offers the benefit of measuring gastric, small bowel, and colonic transit times in a single examination. The WMC also provides intraluminal pressure readings throughout the digestive tract, offering a noninvasive means by which to assess gastrointestinal motility. The WMC should be considered the transit study of choice for individuals suspected of having altered transit in more than one region of the gastrointestinal tract. This review summarizes the features and performance characteristics of the WMC as well as provides a summary on how this diagnostic modality is most effectively used in the assessment of gastrointestinal symptom complexes due to suspected abnormalities in transit.","author":[{"dropping-particle":"","family":"Saad","given":"Richard J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hasler","given":"William L.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastroenterology and Hepatology","id":"ITEM-1","issue":"12","issued":{"date-parts":[["2011"]]},"page":"795-804","title":"A technical review and clinical assessment of the wireless motility capsule","type":"bill","volume":"7"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>116</sup>","plainTextFormattedCitation":"116","previouslyFormattedCitation":"<sup>116</sup>"},"properties":{"noteIndex":0},"schema":""}116. Although CE has primarily used pH to assess motility, there have been some studies investigating changes in pH as a means to detect disease using CE. In one study of 16 patients with IBS defined by Rome III criteria and 16 age-matched control individuals, no differences in the transit times, gastrointestinal motility and ileal pH were found between the two groups using the SmartPillADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.3748/wjg.v20.i17.5000","ISSN":"1007-9327","PMID":"24803812","abstract":"AIM To ascertain whether caecal pH is different in patients with irritable bowel syndrome (IBS), whose primary symptoms are bloating and distension, to healthy controls. METHODS Motility and pH data were reviewed from 16 patients with Rome III defined IBS and 16 healthy controls, who had undergone a wireless motility capsule (WMC) study using a standardized protocol. Motility measures were anchored around known anatomical landmarks as identified by compartmental pH changes. Sixty-minute epochs were used to quantify antral, duodenal, ileal, caecal and distal colonic contractility. The maximum and minimum pH was measured either side of the ileo-caecal junction. RESULTS No differences were seen in motility parameters, compartmental transit times or maximal ileal pH between the two groups. Caecal pH was significantly lower in patients compared to controls (5.12 ± 0.05 vs 6.16 ± 0.15, P < 0.0001). The ileal:caecal Δchange was greater in patients than controls (-2.63 ± 0.08 vs -1.42 ± 0.11, P < 0.0001). There was a significant correlation between caecal pH and right colonic contractility (r = 0.54, P = 0.002). CONCLUSION Patients with bloating and distension have a lower caecal pH compared to controls. The measurement of caecal pH using the WMC provides a quantifiable biomarker of fermentation potentially identifying those patients that may preferentially benefit from antibiotic or dietary interventions.","author":[{"dropping-particle":"","family":"Farmer","given":"Adam D","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"World Journal of Gastroenterology","id":"ITEM-1","issue":"17","issued":{"date-parts":[["2014","5","7"]]},"page":"5000","title":"Caecal pH is a biomarker of excessive colonic fermentation","type":"article-journal","volume":"20"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>146</sup>","plainTextFormattedCitation":"146","previouslyFormattedCitation":"<sup>147</sup>"},"properties":{"noteIndex":0},"schema":""}146. However, cecal pH was lower in patients than in the control individuals (5.12 ±0.05 vs. 6.16 ±0.15, P < 0.0001), which in turn, meant that the change in the ileo–cecal pH was also greater in patients than in controls (-33.8% ±0.84 vs. -18.7% ±1.5, P < 0.0001). A moderate correlation between cecal pH and right colonic contractibility was also observed (r = 0.54, P = 0.002). The authors observed a correlation between measured values of cecal pH and contractile behavior and theorized that the more acidic environment detected in patients with IBS is attributable to excessive fermentation in the cecum, and associated production of short chain fatty acids. This excessive fermentation is thought to be the cause of the reduced proximal colonic motor activity that was detected. They also suggested that cecal pH measured via CE provides a useful measure of colonic fermentation, which might aid in the classification of patients with a broad spectrum of functional gastrointestinal disorders such as bloating and distension.[H3]Soluble BiomarkersVarious soluble biomarkers can be found within the intestinal lumen, such as proteins, enzymes, microbes and their metabolic productsADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1080/17474124.2017.1373017","ISSN":"1747-4124","author":[{"dropping-particle":"","family":"Cummins","given":"Gerard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yung","given":"Diana E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cox","given":"Ben F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Koulaouzidis","given":"Anastasios","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Desmulliez","given":"Marc P. Y.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cochran","given":"Sandy","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Expert Review of Gastroenterology & Hepatology","id":"ITEM-1","issue":"12","issued":{"date-parts":[["2017","12","2"]]},"page":"1119-1134","title":"Luminally expressed gastrointestinal biomarkers","type":"article-journal","volume":"11"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>147</sup>","plainTextFormattedCitation":"147","previouslyFormattedCitation":"<sup>148</sup>"},"properties":{"noteIndex":0},"schema":""}147. Some attempts have been made to integrate sensors for the detection of these substances in CE devices. Up to now, these sensors have utilized either electrochemicalADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/TBME.2011.2158543","ISSN":"0018-9294","PMID":"21642037","abstract":"A characterization of gastrointestinal fluids has been performed by means of an electrochemical sensor that has potential for clinical in vivo and in vitro monitoring applications. The sensor comprised a three-electrode cell with a counter, reference, and four working electrodes, Au, Pt, Ir, and Rh. Cyclic voltammetry was used to obtain chemical information from faecal water (in vitro) and gut model (in vivo) fluids. Stable voltammetric responses were obtained for both fluids at these noble metal working electrodes. The responses differed in shape that demonstrated the discrimination capability and the potential for practical use as a tool for gastrointestinal fluid investigation. The analysis of the stability profiles in faecal water over a 14-h duration has indicated a possible adsorption mechanism with the formation of a biolayer on the sensor surface. The stability in gut model fluids over a 42-h duration has demonstrated a more stable profile, but the mechanisms involved are more complicated to determine.","author":[{"dropping-particle":"","family":"Twomey","given":"Karen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Alvarez de Eulate","given":"Eva","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Marchesi","given":"Julian R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kolida","given":"Sofia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gibson","given":"Glenn","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Arrigan","given":"Damien W. M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ogurtsov","given":"Vladimir I.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Transactions on Biomedical Engineering","id":"ITEM-1","issue":"9","issued":{"date-parts":[["2011","9"]]},"page":"2521-2527","title":"Characterization of the Electrochemical Behavior of Gastrointestinal Fluids Using a Multielectrode Sensor Probe","type":"article-journal","volume":"58"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1016/j.snb.2015.04.063","ISBN":"0925-4005","ISSN":"09254005","abstract":"The gastrointestinal (GI) tract, especially the small intestine, remains largely inaccessible to modern medical science. While swallowable capsule technologies are emerging, endoscopy and colonoscopy remain the primary method for GI tract analysis. This paper presents an alternative wireless device, with electrochemical sensing technique, which behaves autonomously as it travels through the GI tract. The capsule includes a direct access, multi electrode electronic tongue sensor that enables non-specific characterization of gut fluids, aiding in the diagnosis of gastrointestinal diseases such as Crohn's and ulcerative colitis. The sensor, interfaced through a potentiostatic circuit, is capable of performing various voltammetries such as cyclic, square wave and differential pulse techniques. A wireless communication link, operating at 433MHz, delivers measured data to a base station receiver located outside the body. The capsule, powered by a single lithium-ion cell and implemented on a polyimide flexible substrate, is encapsulated in polyether ether ketone (PEEK) material to measure 12mm in diameter and 28mm in length taking volume of approximately 4cm3. The capsule's front end potentiostat compares well with commercial laboratory equipment under the same cell and voltammetry conditions. The electrochemical characterization of the system and its application for electrochemical examination of faecal waters proves its potential as an in vivo GI tract diagnostic tool and other biomedical applications requiring a miniaturized low power sensing device.","author":[{"dropping-particle":"","family":"Caffrey","given":"C. Mc","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Twomey","given":"K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ogurtsov","given":"V.I.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Sensors and Actuators B: Chemical","id":"ITEM-2","issued":{"date-parts":[["2015","10"]]},"page":"8-15","publisher":"Elsevier B.V.","title":"Development of a wireless swallowable capsule with potentiostatic electrochemical sensor for gastrointestinal track investigation","type":"article-journal","volume":"218"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>148,149</sup>","plainTextFormattedCitation":"148,149","previouslyFormattedCitation":"<sup>149,150</sup>"},"properties":{"noteIndex":0},"schema":""}148,149 or opticalADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/JSEN.2016.2633435","ISSN":"1530-437X","author":[{"dropping-particle":"","family":"Yen","given":"Yi-Kuang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Capua","given":"Eyal","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Naaman","given":"Ron","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Sensors Journal","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2017","2","1"]]},"page":"660-666","title":"Application of a GaAs-Based Sensor for Detecting Hemoglobin in Gastrointestinal Environments","type":"article-journal","volume":"17"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1016/j.bios.2015.11.073","ISSN":"09565663","PMID":"26667093","abstract":"Acute upper gastrointestinal bleedings from ulcers or esophago-gastric varices are life threatening medical conditions which require immediate endoscopic therapy. Despite successful endoscopic hemostasis, there is a significant risk of rebleeding often requiring close surveillance of these patients in the intensive care unit (ICU). Any time delay to recognize bleeding may lead to a high blood loss and increases the risk of death. A novel telemetric real-time bleeding sensor can help indicate blood in the stomach: the sensor is swallowed to detect active bleeding or is anchored endoscopically on the gastrointestinal wall close to the potential bleeding source. By telemetric communication with an extra-corporeal receiver, information about the bleeding status is displayed. In this study the novel sensor, which measures characteristic optical properties of blood, has been evaluated in an ex-vivo setting to assess its clinical applicability and usability. Human venous blood of different concentrations, various fluids, and liquid food were tested. The LED-based sensor was able to reliably distinguish between concentrated blood and other liquids, especially red-colored fluids. In addition, the spectrometric quality of the small sensor (size: 6.5 mm in diameter, 25.5 mm in length) was comparable to a much larger and technically more complex laboratory spectrophotometer. The experimental data confirm the capability of a miniaturized sensor to identify concentrated blood, which could help in the very near future the detection of upper gastrointestinal bleeding and to survey high-risk patients for rebleeding.","author":[{"dropping-particle":"","family":"Schostek","given":"Sebastian","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zimmermann","given":"Melanie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Keller","given":"Jan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fode","given":"Mario","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Melbert","given":"Michael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schurr","given":"Marc O.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gottwald","given":"Thomas","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Prosst","given":"Ruediger L.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Biosensors and Bioelectronics","id":"ITEM-2","issued":{"date-parts":[["2016","4"]]},"page":"524-529","publisher":"Elsevier","title":"Telemetric real-time sensor for the detection of acute upper gastrointestinal bleeding","type":"article-journal","volume":"78"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1371/journal.pone.0166488","ISSN":"1932-6203","abstract":"There are no ideal means for the diagnosis of intestinal bleeding diseases as of now, particularly in the small intestine. This study investigated an intelligent intestinal bleeding detection capsule system based on color recognition. After the capsule is swallowed, the bleeding detection module (containing a color-sensitive adsorptive film that changes color when absorbing intestinal juice,) is used to identify intestinal bleeding features. A hue-saturation-light color space method can be applied to detect bleeding according to the range of H and S values of the film color. Once bleeding features are recognized, a wireless transmission module is activated immediately to send an alarm signal to the outside; an in vitro module receives the signal and sends an alarm. The average power consumption of the entire capsule system is estimated to be about 2.1mW. Owing to its simplicity, reliability, and effectiveness, this system represents a new approach to the clinical diagnosis of intestinal bleeding diseases.","author":[{"dropping-particle":"","family":"Qiao","given":"Panpan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Liu","given":"Hongying","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yan","given":"Xueping","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jia","given":"Ziru","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pi","given":"Xitian","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"PLOS ONE","editor":[{"dropping-particle":"","family":"Song","given":"Houbing","non-dropping-particle":"","parse-names":false,"suffix":""}],"id":"ITEM-3","issue":"11","issued":{"date-parts":[["2016","11","30"]]},"page":"e0166488","title":"A Smart Capsule System for Automated Detection of Intestinal Bleeding Using HSL Color Recognition","type":"article-journal","volume":"11"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>150–152</sup>","plainTextFormattedCitation":"150–152","previouslyFormattedCitation":"<sup>151–153</sup>"},"properties":{"noteIndex":0},"schema":""}150–152 methods. The single electrochemical sensing capsuleADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/TBME.2011.2158543","ISSN":"0018-9294","PMID":"21642037","abstract":"A characterization of gastrointestinal fluids has been performed by means of an electrochemical sensor that has potential for clinical in vivo and in vitro monitoring applications. The sensor comprised a three-electrode cell with a counter, reference, and four working electrodes, Au, Pt, Ir, and Rh. Cyclic voltammetry was used to obtain chemical information from faecal water (in vitro) and gut model (in vivo) fluids. Stable voltammetric responses were obtained for both fluids at these noble metal working electrodes. The responses differed in shape that demonstrated the discrimination capability and the potential for practical use as a tool for gastrointestinal fluid investigation. The analysis of the stability profiles in faecal water over a 14-h duration has indicated a possible adsorption mechanism with the formation of a biolayer on the sensor surface. The stability in gut model fluids over a 42-h duration has demonstrated a more stable profile, but the mechanisms involved are more complicated to determine.","author":[{"dropping-particle":"","family":"Twomey","given":"Karen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Alvarez de Eulate","given":"Eva","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Marchesi","given":"Julian R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kolida","given":"Sofia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gibson","given":"Glenn","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Arrigan","given":"Damien W. M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ogurtsov","given":"Vladimir I.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Transactions on Biomedical Engineering","id":"ITEM-1","issue":"9","issued":{"date-parts":[["2011","9"]]},"page":"2521-2527","title":"Characterization of the Electrochemical Behavior of Gastrointestinal Fluids Using a Multielectrode Sensor Probe","type":"article-journal","volume":"58"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1016/j.snb.2015.04.063","ISBN":"0925-4005","ISSN":"09254005","abstract":"The gastrointestinal (GI) tract, especially the small intestine, remains largely inaccessible to modern medical science. While swallowable capsule technologies are emerging, endoscopy and colonoscopy remain the primary method for GI tract analysis. This paper presents an alternative wireless device, with electrochemical sensing technique, which behaves autonomously as it travels through the GI tract. The capsule includes a direct access, multi electrode electronic tongue sensor that enables non-specific characterization of gut fluids, aiding in the diagnosis of gastrointestinal diseases such as Crohn's and ulcerative colitis. The sensor, interfaced through a potentiostatic circuit, is capable of performing various voltammetries such as cyclic, square wave and differential pulse techniques. A wireless communication link, operating at 433MHz, delivers measured data to a base station receiver located outside the body. The capsule, powered by a single lithium-ion cell and implemented on a polyimide flexible substrate, is encapsulated in polyether ether ketone (PEEK) material to measure 12mm in diameter and 28mm in length taking volume of approximately 4cm3. The capsule's front end potentiostat compares well with commercial laboratory equipment under the same cell and voltammetry conditions. The electrochemical characterization of the system and its application for electrochemical examination of faecal waters proves its potential as an in vivo GI tract diagnostic tool and other biomedical applications requiring a miniaturized low power sensing device.","author":[{"dropping-particle":"","family":"Caffrey","given":"C. Mc","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Twomey","given":"K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ogurtsov","given":"V.I.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Sensors and Actuators B: Chemical","id":"ITEM-2","issued":{"date-parts":[["2015","10"]]},"page":"8-15","publisher":"Elsevier B.V.","title":"Development of a wireless swallowable capsule with potentiostatic electrochemical sensor for gastrointestinal track investigation","type":"article-journal","volume":"218"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>148,149</sup>","plainTextFormattedCitation":"148,149","previouslyFormattedCitation":"<sup>149,150</sup>"},"properties":{"noteIndex":0},"schema":""}148,149 incorporates a multi-electrode sensor with onboard potentiostatic circuits [G] to enable cyclic and pulsed voltammetry [G] of the gastrointestinal fluid surrounding the capsule. To date, these capsules have been tested only in vitro using fecal water to demonstrate repeatable and reliable measurement. However, the shapes of voltammograms [G] produced by the metal electrodes of the electrochemical sensors were shown to change with timeADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/TBME.2011.2158543","ISSN":"0018-9294","PMID":"21642037","abstract":"A characterization of gastrointestinal fluids has been performed by means of an electrochemical sensor that has potential for clinical in vivo and in vitro monitoring applications. The sensor comprised a three-electrode cell with a counter, reference, and four working electrodes, Au, Pt, Ir, and Rh. Cyclic voltammetry was used to obtain chemical information from faecal water (in vitro) and gut model (in vivo) fluids. Stable voltammetric responses were obtained for both fluids at these noble metal working electrodes. The responses differed in shape that demonstrated the discrimination capability and the potential for practical use as a tool for gastrointestinal fluid investigation. The analysis of the stability profiles in faecal water over a 14-h duration has indicated a possible adsorption mechanism with the formation of a biolayer on the sensor surface. The stability in gut model fluids over a 42-h duration has demonstrated a more stable profile, but the mechanisms involved are more complicated to determine.","author":[{"dropping-particle":"","family":"Twomey","given":"Karen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Alvarez de Eulate","given":"Eva","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Marchesi","given":"Julian R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kolida","given":"Sofia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gibson","given":"Glenn","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Arrigan","given":"Damien W. M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ogurtsov","given":"Vladimir I.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Transactions on Biomedical Engineering","id":"ITEM-1","issue":"9","issued":{"date-parts":[["2011","9"]]},"page":"2521-2527","title":"Characterization of the Electrochemical Behavior of Gastrointestinal Fluids Using a Multielectrode Sensor Probe","type":"article-journal","volume":"58"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>148</sup>","plainTextFormattedCitation":"148","previouslyFormattedCitation":"<sup>149</sup>"},"properties":{"noteIndex":0},"schema":""}148. This result was partially attributed to the adsorption of organic matter onto the electrode surface, which would result in a reduced effective area for the electrochemical reactions used to sense the surrounding gastrointestinal fluid. Mass transfer of the analyte to the sensor surface determines the response of electrochemical sensors. Hence, a change in surface area of the working electrode could potentially lead to erroneous measurement of the concentration of the constituent soluble biomarkers of interest, raising questions about the long-term stability of these devices. The design of optical sensing capsules has been focused on detection of gastrointestinal bleeding using colorimetryADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1371/journal.pone.0166488","ISSN":"1932-6203","abstract":"There are no ideal means for the diagnosis of intestinal bleeding diseases as of now, particularly in the small intestine. This study investigated an intelligent intestinal bleeding detection capsule system based on color recognition. After the capsule is swallowed, the bleeding detection module (containing a color-sensitive adsorptive film that changes color when absorbing intestinal juice,) is used to identify intestinal bleeding features. A hue-saturation-light color space method can be applied to detect bleeding according to the range of H and S values of the film color. Once bleeding features are recognized, a wireless transmission module is activated immediately to send an alarm signal to the outside; an in vitro module receives the signal and sends an alarm. The average power consumption of the entire capsule system is estimated to be about 2.1mW. Owing to its simplicity, reliability, and effectiveness, this system represents a new approach to the clinical diagnosis of intestinal bleeding diseases.","author":[{"dropping-particle":"","family":"Qiao","given":"Panpan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Liu","given":"Hongying","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yan","given":"Xueping","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jia","given":"Ziru","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pi","given":"Xitian","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"PLOS ONE","editor":[{"dropping-particle":"","family":"Song","given":"Houbing","non-dropping-particle":"","parse-names":false,"suffix":""}],"id":"ITEM-1","issue":"11","issued":{"date-parts":[["2016","11","30"]]},"page":"e0166488","title":"A Smart Capsule System for Automated Detection of Intestinal Bleeding Using HSL Color Recognition","type":"article-journal","volume":"11"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>152</sup>","plainTextFormattedCitation":"152","previouslyFormattedCitation":"<sup>153</sup>"},"properties":{"noteIndex":0},"schema":""}152, spectroscopyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.bios.2015.11.073","ISSN":"09565663","PMID":"26667093","abstract":"Acute upper gastrointestinal bleedings from ulcers or esophago-gastric varices are life threatening medical conditions which require immediate endoscopic therapy. Despite successful endoscopic hemostasis, there is a significant risk of rebleeding often requiring close surveillance of these patients in the intensive care unit (ICU). Any time delay to recognize bleeding may lead to a high blood loss and increases the risk of death. A novel telemetric real-time bleeding sensor can help indicate blood in the stomach: the sensor is swallowed to detect active bleeding or is anchored endoscopically on the gastrointestinal wall close to the potential bleeding source. By telemetric communication with an extra-corporeal receiver, information about the bleeding status is displayed. In this study the novel sensor, which measures characteristic optical properties of blood, has been evaluated in an ex-vivo setting to assess its clinical applicability and usability. Human venous blood of different concentrations, various fluids, and liquid food were tested. The LED-based sensor was able to reliably distinguish between concentrated blood and other liquids, especially red-colored fluids. In addition, the spectrometric quality of the small sensor (size: 6.5 mm in diameter, 25.5 mm in length) was comparable to a much larger and technically more complex laboratory spectrophotometer. The experimental data confirm the capability of a miniaturized sensor to identify concentrated blood, which could help in the very near future the detection of upper gastrointestinal bleeding and to survey high-risk patients for rebleeding.","author":[{"dropping-particle":"","family":"Schostek","given":"Sebastian","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zimmermann","given":"Melanie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Keller","given":"Jan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fode","given":"Mario","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Melbert","given":"Michael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schurr","given":"Marc O.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gottwald","given":"Thomas","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Prosst","given":"Ruediger L.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Biosensors and Bioelectronics","id":"ITEM-1","issued":{"date-parts":[["2016","4"]]},"page":"524-529","publisher":"Elsevier","title":"Telemetric real-time sensor for the detection of acute upper gastrointestinal bleeding","type":"article-journal","volume":"78"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>151</sup>","plainTextFormattedCitation":"151","previouslyFormattedCitation":"<sup>152</sup>"},"properties":{"noteIndex":0},"schema":""}151 or fluoroscopyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1039/C5LC00770D","ISBN":"1473-0197","ISSN":"1473-0197","PMID":"26490455","abstract":"A swallowable, capsular fluorometer simplifies detection of upper gastrointestinal bleeding by wirelessly detecting presence of fluorescein-spiked blood in the stomach.","author":[{"dropping-particle":"","family":"Nemiroski","given":"Alex","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ryou","given":"Marvin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Thompson","given":"Christopher C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Westervelt","given":"Robert M.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Lab on a Chip","id":"ITEM-1","issue":"23","issued":{"date-parts":[["2015"]]},"page":"4479-4487","title":"Swallowable fluorometric capsule for wireless triage of gastrointestinal bleeding","type":"article-journal","volume":"15"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>83</sup>","plainTextFormattedCitation":"83","previouslyFormattedCitation":"<sup>83</sup>"},"properties":{"noteIndex":0},"schema":""}83. The colorimetric CE system developed by Qiao et al.ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1371/journal.pone.0166488","ISSN":"1932-6203","abstract":"There are no ideal means for the diagnosis of intestinal bleeding diseases as of now, particularly in the small intestine. This study investigated an intelligent intestinal bleeding detection capsule system based on color recognition. After the capsule is swallowed, the bleeding detection module (containing a color-sensitive adsorptive film that changes color when absorbing intestinal juice,) is used to identify intestinal bleeding features. A hue-saturation-light color space method can be applied to detect bleeding according to the range of H and S values of the film color. Once bleeding features are recognized, a wireless transmission module is activated immediately to send an alarm signal to the outside; an in vitro module receives the signal and sends an alarm. The average power consumption of the entire capsule system is estimated to be about 2.1mW. Owing to its simplicity, reliability, and effectiveness, this system represents a new approach to the clinical diagnosis of intestinal bleeding diseases.","author":[{"dropping-particle":"","family":"Qiao","given":"Panpan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Liu","given":"Hongying","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yan","given":"Xueping","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jia","given":"Ziru","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pi","given":"Xitian","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"PLOS ONE","editor":[{"dropping-particle":"","family":"Song","given":"Houbing","non-dropping-particle":"","parse-names":false,"suffix":""}],"id":"ITEM-1","issue":"11","issued":{"date-parts":[["2016","11","30"]]},"page":"e0166488","title":"A Smart Capsule System for Automated Detection of Intestinal Bleeding Using HSL Color Recognition","type":"article-journal","volume":"11"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>152</sup>","plainTextFormattedCitation":"152","previouslyFormattedCitation":"<sup>153</sup>"},"properties":{"noteIndex":0},"schema":""}152 used a hue–saturation light color detection method on blood cells selectively channeled into a measurement chamber. This chamber included white LEDs for illumination, a colour sensor and an adsorptive colour-sensitive film that undergoes a change from white to red in the presence of hemoglobin. In vitro trials with different blood concentrations showed that the system could measure hemoglobin concentrations as low as 2.375?mg per ml, which is reported to be less than that found in areas of gastrointestinal bleedingGIBADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/S0002-9270(00)02414-X","ISBN":"0002-9270 (Print)\r0002-9270 (Linking)","ISSN":"00029270","PMID":"11280550","abstract":"OBJECTIVES: We investigated whether the mean platelet volume would be a useful marker in the evaluation of inflammatory bowel disease activity. METHODS: Complete blood count, C-reactive protein, erythrocyte sedimentation rate, serum thrombopoietin and erythropoietin, plasma β-thromboglobulin, and platelet factor 4 were measured in 93 patients with ulcerative colitis, 66 patients with Crohn’s disease, and 38 healthy blood donors. Disease activity was assessed by the Clinical Colitis Activity Index in patients with ulcerative colitis and by the Crohn’s Disease Activity Index in patients with Crohn’s disease. RESULTS: Mean platelet count was increased in patients with active compared to inactive ulcerative colitis (p < 0.05), and in patients with active compared to inactive Crohn’s disease (p = 0.0002) or healthy controls (p < 0.0001). On the other hand, mean platelet volume was significantly decreased in patients with active compared to inactive ulcerative colitis (p = 0.02) or healthy controls (p < 0.0001), and in patients with active compared to inactive Crohn’s disease (p = 0.0005) or healthy controls (p < 0.0001). Mean platelet volume was inversely correlated with the white blood cell count (r = -0.17, p = 0.02), C-reactive protein (r = -0.46, p = 0.009) and erythrocyte sedimentation rate (r = -0.28, p = 0.008). No significant correlations were found between mean platelet volume and serum thrombopoietin or erythropoietin levels; however, a strong negative correlation between mean platelet volume and β-thromboglobulin (r = -0.34, p < 0.0001) and platelet factor 4 (r = -0.30, p = 0.0002) was observed. CONCLUSIONS: Mean platelet volume is significantly reduced in active inflammatory bowel disease and is negatively correlated with the known inflammatory bowel disease activity markers and the platelet activation products. We propose that mean platelet volume provides a useful marker of activity in inflammatory bowel disease. ? 2001 by Am. Coll. of Gastroenterology.","author":[{"dropping-particle":"","family":"Kapsoritakis","given":"Andreas N.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Koukourakis","given":"Michael I.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sfiridaki","given":"Aekaterini","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Potamianos","given":"Spiros P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kosmadaki","given":"Maria G.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Koutroubakis","given":"Ioannis E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kouroumalis","given":"Elias A.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"American Journal of Gastroenterology","id":"ITEM-1","issued":{"date-parts":[["2001"]]},"title":"Mean platelet volume: A useful marker of inflammatory bowel disease activity","type":"article-journal"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>153</sup>","plainTextFormattedCitation":"153","previouslyFormattedCitation":"<sup>154</sup>"},"properties":{"noteIndex":0},"schema":""}153. The wireless spectroscopic HemoPillADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.bios.2015.11.073","ISSN":"09565663","PMID":"26667093","abstract":"Acute upper gastrointestinal bleedings from ulcers or esophago-gastric varices are life threatening medical conditions which require immediate endoscopic therapy. Despite successful endoscopic hemostasis, there is a significant risk of rebleeding often requiring close surveillance of these patients in the intensive care unit (ICU). Any time delay to recognize bleeding may lead to a high blood loss and increases the risk of death. A novel telemetric real-time bleeding sensor can help indicate blood in the stomach: the sensor is swallowed to detect active bleeding or is anchored endoscopically on the gastrointestinal wall close to the potential bleeding source. By telemetric communication with an extra-corporeal receiver, information about the bleeding status is displayed. In this study the novel sensor, which measures characteristic optical properties of blood, has been evaluated in an ex-vivo setting to assess its clinical applicability and usability. Human venous blood of different concentrations, various fluids, and liquid food were tested. The LED-based sensor was able to reliably distinguish between concentrated blood and other liquids, especially red-colored fluids. In addition, the spectrometric quality of the small sensor (size: 6.5 mm in diameter, 25.5 mm in length) was comparable to a much larger and technically more complex laboratory spectrophotometer. The experimental data confirm the capability of a miniaturized sensor to identify concentrated blood, which could help in the very near future the detection of upper gastrointestinal bleeding and to survey high-risk patients for rebleeding.","author":[{"dropping-particle":"","family":"Schostek","given":"Sebastian","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zimmermann","given":"Melanie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Keller","given":"Jan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fode","given":"Mario","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Melbert","given":"Michael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schurr","given":"Marc O.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gottwald","given":"Thomas","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Prosst","given":"Ruediger L.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Biosensors and Bioelectronics","id":"ITEM-1","issued":{"date-parts":[["2016","4"]]},"page":"524-529","publisher":"Elsevier","title":"Telemetric real-time sensor for the detection of acute upper gastrointestinal bleeding","type":"article-journal","volume":"78"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>151</sup>","plainTextFormattedCitation":"151","previouslyFormattedCitation":"<sup>152</sup>"},"properties":{"noteIndex":0},"schema":""}151 (OVESCO, Tuebingen, Germany) has been tested in a preliminary human trialADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1007/s10620-016-4226-y","ISSN":"0163-2116","author":[{"dropping-particle":"","family":"Schostek","given":"Sebastian","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zimmermann","given":"Melanie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Keller","given":"Jan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fode","given":"Mario","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Melbert","given":"Michael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schurr","given":"Marc O.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gottwald","given":"Thomas","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Prosst","given":"Ruediger L.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Digestive Diseases and Sciences","id":"ITEM-1","issue":"10","issued":{"date-parts":[["2016","10","24"]]},"page":"2956-2962","title":"Volunteer Case Series of a New Telemetric Sensor for Blood Detection in the Upper Gastrointestinal Tract: The HemoPill","type":"article-journal","volume":"61"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>154</sup>","plainTextFormattedCitation":"154","previouslyFormattedCitation":"<sup>155</sup>"},"properties":{"noteIndex":0},"schema":""}154. The battery-powered capsule is 6.5?mm in diameter, 25.5 mm long and contains an optical sensor to measure the optical absorption at 415?nm between an LED and a photodetector across a recessed channel. At this wavelength optical transmission through blood is at a minimum and is three orders of magnitude less than transmission at a reference wavelength (720?nm). The optical sensor compares the change in absorption at 415?nm to the reference signal at 720?nm to detect haemoglobin. Initial tests were performed on a healthy volunteer with simulated gastrointestinal bleeding under a variety of conditions through periodic ingestion of 20?ml blood. The results were compared with baseline readings from the same volunteer under the same conditions without blood intake. The capsule successfully detected simulated gastrointestinal bleeding after each ingestion of blood, with the detection algorithm showing a correlation (R2?=?0.9016) between changing sensor signal within 10?min of capsule ingestion and increased gastric blood concentration.In 2018, Mimee et al. reported the development of a wireless capsule able to detect gastrointestinal bleeding in a porcine model using genetically engineered bacteria that luminesce in the presence of bloodADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1126/science.aas9315","ISSN":"0036-8075","author":[{"dropping-particle":"","family":"Mimee","given":"Mark","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nadeau","given":"Phillip","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hayward","given":"Alison","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Carim","given":"Sean","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Flanagan","given":"Sarah","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jerger","given":"Logan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Collins","given":"Joy","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"McDonnell","given":"Shane","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Swartwout","given":"Richard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Citorik","given":"Robert J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bulovi?","given":"Vladimir","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Langer","given":"Robert","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Traverso","given":"Giovanni","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chandrakasan","given":"Anantha P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lu","given":"Timothy K.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Science","id":"ITEM-1","issue":"6391","issued":{"date-parts":[["2018","5","25"]]},"page":"915-918","title":"An ingestible bacterial-electronic system to monitor gastrointestinal health","type":"article-journal","volume":"360"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>155</sup>","plainTextFormattedCitation":"155","previouslyFormattedCitation":"<sup>156</sup>"},"properties":{"noteIndex":0},"schema":""}155. The Escherichia coli bacteria were also modified to enable the detection of thiosulfate and acyl-homoserine lactone, which are potential biomarkers of gut inflammation and infectious bacteria, respectively ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1126/science.aas9315","ISSN":"0036-8075","author":[{"dropping-particle":"","family":"Mimee","given":"Mark","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nadeau","given":"Phillip","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hayward","given":"Alison","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Carim","given":"Sean","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Flanagan","given":"Sarah","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jerger","given":"Logan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Collins","given":"Joy","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"McDonnell","given":"Shane","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Swartwout","given":"Richard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Citorik","given":"Robert J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bulovi?","given":"Vladimir","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Langer","given":"Robert","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Traverso","given":"Giovanni","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chandrakasan","given":"Anantha P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lu","given":"Timothy K.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Science","id":"ITEM-1","issue":"6391","issued":{"date-parts":[["2018","5","25"]]},"page":"915-918","title":"An ingestible bacterial-electronic system to monitor gastrointestinal health","type":"article-journal","volume":"360"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>155</sup>","plainTextFormattedCitation":"155","previouslyFormattedCitation":"<sup>156</sup>"},"properties":{"noteIndex":0},"schema":""}155. [H3]Gases and volatile organic compounds The gut microbiome is a vast community of diverse microorganisms that is important for intestinal homeostasis and is linked to diseases such as IBD and CRC ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1080/17474124.2017.1373017","ISSN":"1747-4124","author":[{"dropping-particle":"","family":"Cummins","given":"Gerard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yung","given":"Diana E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cox","given":"Ben F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Koulaouzidis","given":"Anastasios","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Desmulliez","given":"Marc P. 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However, studies have shown some difference between fecal and gut microbiomesADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1371/journal.pone.0016952","ISBN":"1932-6203 (Electronic) 1932-6203 (Linking)","ISSN":"19326203","PMID":"21347324","abstract":"BACKGROUND: The characterization of the human intestinal microflora and their interactions with the host have been identified as key components in the study of intestinal disorders such as inflammatory bowel diseases. High-throughput sequencing has enabled culture-independent studies to deeply analyze bacteria in the gut. It is possible with this technology to systematically analyze links between microbes and the genetic constitution of the host, such as DNA polymorphisms and methylation, and gene expression.\\n\\nMETHODS AND FINDINGS: In this study the V2 region of the bacterial 16S ribosomal RNA (rRNA) gene using 454 pyrosequencing from seven anatomic regions of human colon and two types of stool specimens were analyzed. The study examined the number of reads needed to ascertain differences between samples, the effect of DNA extraction procedures and PCR reproducibility, and differences between biopsies and stools in order to design a large scale systematic analysis of gut microbes. It was shown (1) that sequence coverage lower than 1,000 reads influenced quantitative and qualitative differences between samples measured by UniFrac distances. Distances between samples became stable after 1,000 reads. (2) Difference of extracted bacteria was observed between the two DNA extraction methods. In particular, Firmicutes Bacilli were not extracted well by one method. (3) Quantitative and qualitative difference in bacteria from ileum to rectum colon were not observed, but there was a significant positive trend between distances within colon and quantitative differences. Between sample type, biopsies or stools, quantitative and qualitative differences were observed.\\n\\nCONCLUSIONS: Results of human colonic bacteria analyzed using high-throughput sequencing were highly dependent on the experimental design, especially the number of sequence reads, DNA extraction method, and sample type.","author":[{"dropping-particle":"","family":"Momozawa","given":"Yukihide","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Deffontaine","given":"Valérie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Louis","given":"Edouard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Medrano","given":"Juan F.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"PLoS ONE","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2011"]]},"title":"Characterization of bacteria in biopsies of colon and stools by high throughput sequencing of the V2 region of bacterial 16s rRNA gene in human","type":"article-journal","volume":"6"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>156</sup>","plainTextFormattedCitation":"156","previouslyFormattedCitation":"<sup>157</sup>"},"properties":{"noteIndex":0},"schema":""}156. Indirect measurement of the microbiome could be achieved by monitoring their metabolic byproductsADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1080/17474124.2017.1373017","ISSN":"1747-4124","author":[{"dropping-particle":"","family":"Cummins","given":"Gerard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yung","given":"Diana E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cox","given":"Ben F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Koulaouzidis","given":"Anastasios","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Desmulliez","given":"Marc P. 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The microbial ecosystem and its interaction with the host are described, along with recent attempts to manipulate the composition and activity of the microbial community by adding antibiotics and other chemicals to ruminant diets. A similar microbial community and fermentation occur in the large intestine or cecum of most nonruminant animals including the large intestine of humans. The microbial ecosystems of the rumen and human large intestine are compared.","author":[{"dropping-particle":"","family":"Wolin","given":"M. J","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Science","id":"ITEM-1","issue":"4515","issued":{"date-parts":[["1981","9","25"]]},"page":"1463-1468","title":"Fermentation in the rumen and human large intestine","type":"article-journal","volume":"213"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>157</sup>","plainTextFormattedCitation":"157","previouslyFormattedCitation":"<sup>158</sup>"},"properties":{"noteIndex":0},"schema":""}157.Kalantar-Zadeh et al. developed a wireless CE device that was successfully used to provide real-time measurements of the level of gases such as hydrogen, carbon dioxide and oxygen along the gastrointestinal tract in five human volunteersADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1038/s41928-017-0004-x","ISBN":"2520-1131","ISSN":"2520-1131","abstract":"Ingestible sensors are potentially a powerful tool for monitoring human health. Sensors have been developed that can, for example, provide pH and pressure readings or monitor medication, but capsules that can provide key information about the chemical composition of the gut are still not available. Here we report a human pilot trial of an ingestible electronic capsule that can sense oxygen, hydrogen, and carbon dioxide. The capsule uses a combination of thermal conductivity and semiconducting sensors, and their selectivity and sensitivity to different gases is controlled by adjusting the heating elements of the sensors. Gas profiles of the subjects were obtained while modulating gut microbial fermentative activities by altering their intake of dietary fibre. Ultrasound imaging confirmed that the oxygen-equivalent concentration profile could be used as an accurate marker for the location of the capsule. In a crossover study, variations of fibre intake were found to be associated with differing small intestinal and colonic transit times, and gut fermentation. Regional fermentation patterns could be defined via hydrogen gas profiles. Our gas capsule offers an accurate and safe tool for monitoring the effects of diet of individuals, and has the potential to be used as a diagnostic tool for the gut.","author":[{"dropping-particle":"","family":"Kalantar-Zadeh","given":"Kourosh","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Berean","given":"Kyle J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ha","given":"Nam","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chrimes","given":"Adam F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Xu","given":"Kai","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Grando","given":"Danilla","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ou","given":"Jian Zhen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pillai","given":"Naresh","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Campbell","given":"Jos L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Brklja?a","given":"Robert","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Taylor","given":"Kirstin M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Burgell","given":"Rebecca E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yao","given":"Chu K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ward","given":"Stephanie A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"McSweeney","given":"Chris S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Muir","given":"Jane G.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gibson","given":"Peter R.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Nature Electronics","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2018"]]},"page":"79-87","publisher":"Springer US","title":"A human pilot trial of ingestible electronic capsules capable of sensing different gases in the gut","type":"article-journal","volume":"1"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>158</sup>","plainTextFormattedCitation":"158","previouslyFormattedCitation":"<sup>159</sup>"},"properties":{"noteIndex":0},"schema":""}158. The 9.8?mm diameter, 26?mm long capsules included a non-specific, semiconducting metal oxide sensor responsive to all oxidizing gases under aerobic and anaerobic conditions. This sensor was calibrated to detect hydrogen, carbon dioxide and oxygen. Intestinal gas entered the capsule through a semi-permeable membrane containing embedded nanoparticles that excluded water. The capsule was capable of operating for more than 4four days, and its excretion could be detected using an onboard temperature sensor. Capsule localization was achieved by measuring oxygen concentration levels throughout the gastrointestinal tract. This localization method successfully detected the gastric, small and large intestinal transit times for solid food. Recording the changing levels of hydrogen provided a means of understanding the microbial fermentation of food in the gut, the anaerobic process by which most small bowel and colonic microbiota obtain energy. However, attempts to correlate the changing levels of gas with diet types and fecal microbiomes of the volunteers were inconclusive. The accuracy of hydrogen and oxygen measurements was better than 0.2%, whereas the accuracy of carbon dioxide measurements was 1%. This capsule was a refinement of a device that had been tested in animal modelsADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1053/j.gastro.2015.07.072","ISSN":"00165085","author":[{"dropping-particle":"","family":"Kalantar-zadeh","given":"Kourosh","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yao","given":"Chu K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Berean","given":"Kyle J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ha","given":"Nam","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ou","given":"Jian Zhen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ward","given":"Stephanie A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pillai","given":"Naresh","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hill","given":"Julian","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cottrell","given":"Jeremy J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dunshea","given":"Frank R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"McSweeney","given":"Chris","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Muir","given":"Jane G.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gibson","given":"Peter R.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastroenterology","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2016","1"]]},"page":"37-39","title":"Intestinal Gas Capsules: A Proof-of-Concept Demonstration","type":"article-journal","volume":"150"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1038/srep33387","ISSN":"20452322","abstract":"? 2016 The Author(s). Gastroenterologists are still unable to differentiate between some of the most ordinary disorders of the gut and consequently patients are misdiagnosed. We have developed a swallowable gas sensor capsule for addressing this. The gases of the gut are the by-product of the fermentation processes during digestion, affected by the gut state and can consequently provide the needed information regarding the health of the gut. Here we present the first study on gas sensor capsules for revealing the effect of a medical supplement in an animal (pig) model. We characterise the real-time alterations of gastric-gas in response to environmental heat-stress and dietary cinnamon and use the gas profiles for understanding the bio-physiological changes. Under no heat-stress, feeding increases gastric CO 2 concentration, while dietary cinnamon reduces it due to decrease in gastric acid and pepsin secretion. Alternatively, heat-stress leads to hyperventilation in pigs, which reduces CO 2 concentration and with the cinnamon treatment, CO 2 diminishes even more, resulting in health improvement outcomes. Overall, a good repeatability in gas profiles is also observed. The model demonstrates the strong potential of real-time gas profiler in providing new physiological information that will impact understanding of therapeutics, presenting a highly reliable device for monitoring/diagnostics of gastrointestinal disorders.","author":[{"dropping-particle":"","family":"Ou","given":"Jian Zhen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cottrell","given":"Jeremy J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ha","given":"Nam","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pillai","given":"Naresh","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yao","given":"Chu K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Berean","given":"Kyle J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ward","given":"Stephanie A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Grando","given":"Danilla","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Muir","given":"Jane G.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Harrison","given":"Christopher J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wijesiriwardana","given":"Udani","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dunshea","given":"Frank R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gibson","given":"Peter R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kalantar-Zadeh","given":"Kourosh","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Scientific Reports","id":"ITEM-2","issue":"September","issued":{"date-parts":[["2016"]]},"page":"1-9","publisher":"Nature Publishing Group","title":"Potential of in vivo real-time gastric gas profiling: A pilot evaluation of heat-stress and modulating dietary cinnamon effect in an animal model","type":"article-journal","volume":"6"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>159,160</sup>","plainTextFormattedCitation":"159,160","previouslyFormattedCitation":"<sup>160,161</sup>"},"properties":{"noteIndex":0},"schema":""}159,160, but previous capsules did not have oxygen and temperature sensors and the algorithm used to determine the gas levels was not as accurate in separating overlapping signals from the hydrogen and carbon dioxide sensors. [H1] Trends For Non-WLI Capsules The increasing variety of sensors and imaging technologies adapted for use in conventional and capsule endoscopy is opening up new avenues of research. One area is virtual biopsy, which uses high-resolution transmural imaging technologies to enable in situ, real-time histological examination without the need for a physical biopsy. Virtual biopsy is defined as the ability to make a histological examination by inspection of a site of interest in vivo using specific imaging modalitiesADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.gie.2013.07.035","ISSN":"00165107","PMID":"24342587","author":[{"dropping-particle":"","family":"Deutsch","given":"John C.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastrointestinal Endoscopy","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2014"]]},"page":"64-65","publisher":"Elsevier Ltd","title":"The optical biopsy of small gastric lesions","type":"article-journal","volume":"79"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>161</sup>","plainTextFormattedCitation":"161","previouslyFormattedCitation":"<sup>162</sup>"},"properties":{"noteIndex":0},"schema":""}161. Though Although much of the work done to date has utilized conventional endoscopy because of the wider range of modalities available and absence of miniaturization and integration challenges caused by the space limitations of CEADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.cgh.2013.06.017","ISSN":"15423565","author":[{"dropping-particle":"","family":"Qumseya","given":"Bashar J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wang","given":"Haibo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Badie","given":"Nicole","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Uzomba","given":"Rosemary N.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Parasa","given":"Sravanthi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"White","given":"Donna L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wolfsen","given":"Herbert","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sharma","given":"Prateek","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wallace","given":"Michael B.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Clinical Gastroenterology and Hepatology","id":"ITEM-1","issue":"12","issued":{"date-parts":[["2013","12"]]},"page":"1562-1570.e2","title":"Advanced Imaging Technologies Increase Detection of Dysplasia and Neoplasia in Patients With Barrett's Esophagus: A Meta-analysis and Systematic Review","type":"article-journal","volume":"11"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1111/codi.12033","ISSN":"14628910","author":[{"dropping-particle":"","family":"Su","given":"P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Liu","given":"Y.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lin","given":"S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Xiao","given":"K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chen","given":"P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"An","given":"S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"He","given":"J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bai","given":"Y.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Colorectal Disease","id":"ITEM-2","issue":"1","issued":{"date-parts":[["2013","1"]]},"page":"e1-e12","title":"Efficacy of confocal laser endomicroscopy for discriminating colorectal neoplasms from non-neoplasms: a systematic review and meta-analysis","type":"article-journal","volume":"15"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1097/SLE.0000000000000072","ISSN":"1530-4515","author":[{"dropping-particle":"","family":"Ypsilantis","given":"Efthymios","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pissas","given":"Dimitrios","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Papagrigoriadis","given":"Savvas","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Haji","given":"Amyn","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Surgical Laparoscopy, Endoscopy & Percutaneous Techniques","id":"ITEM-3","issue":"1","issued":{"date-parts":[["2015","2"]]},"page":"1-5","title":"Use of Confocal Laser Endomicroscopy to Assess the Adequacy of Endoscopic Treatment of Gastrointestinal Neoplasia","type":"article-journal","volume":"25"},"uris":[""]},{"id":"ITEM-4","itemData":{"DOI":"10.1155/2016/4638683","ISSN":"2314-6133","abstract":"Confocal laser endomicroscopy (CLE) is an endoscopic-assisted technique developed to obtain histopathological diagnoses of gastrointestinal and pancreatobiliary diseases in real time. The objective of this systematic review is to analyze the current literature on CLE and to evaluate the applicability and diagnostic yield of CLE in patients with gastrointestinal and pancreatobiliary diseases. A literature search was performed on MEDLINE, EMBASE, Scopus, and Cochrane Oral Health Group Specialized Register, using pertinent keywords without time limitations. Both prospective and retrospective clinical studies that evaluated the sensitivity, specificity, or accuracy of CLE were eligible for inclusion. Of 662 articles identified, 102 studies were included in the systematic review. The studies were conducted between 2004 and 2015 in 16 different countries. CLE demonstrated high sensitivity and specificity in the detection of dysplasia in Barrett’s esophagus, gastric neoplasms and polyps, colorectal cancers in inflammatory bowel disease, malignant pancreatobiliary strictures, and pancreatic cysts. 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Further clinical trials with a particular focus on cost-effectiveness and medicoeconomic analyses, as well as standardized institutional training, are advocated to implement CLE in routine clinical practice.","author":[{"dropping-particle":"","family":"Fugazza","given":"Alessandro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gaiani","given":"Federica","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Carra","given":"Maria Clotilde","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Brunetti","given":"Francesco","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lévy","given":"Micha?l","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sobhani","given":"Iradj","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Azoulay","given":"Daniel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Catena","given":"Fausto","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"De’Angelis","given":"Gian Luigi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"De’Angelis","given":"Nicola","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"BioMed Research International","id":"ITEM-4","issued":{"date-parts":[["2016"]]},"page":"1-31","title":"Confocal Laser Endomicroscopy in Gastrointestinal and Pancreatobiliary Diseases: A Systematic Review and Meta-Analysis","type":"article-journal","volume":"2016"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>162–165</sup>","plainTextFormattedCitation":"162–165","previouslyFormattedCitation":"<sup>163–166</sup>"},"properties":{"noteIndex":0},"schema":""}162–165, some efforts that have successfully demonstrated that virtual biopsy is possible in CEADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/TBME.2018.2852715","ISSN":"0018-9294","author":[{"dropping-particle":"","family":"Lay","given":"Holly","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cummins","given":"Gerard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cox","given":"Benjamin F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Qiu","given":"Yongqiang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Turcanu","given":"Mihnea Vlad","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"McPhillips","given":"Rachael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Connor","given":"Ciaran","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gregson","given":"Rachael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Clutton","given":"Eddie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Desmulliez","given":"Marc P.Y.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cochran","given":"Sandy","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Transactions on Biomedical Engineering","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2018"]]},"page":"632 - 639","title":"In-Vivo Evaluation of Microultrasound and Thermometric Capsule Endoscopes","type":"article-journal","volume":"66"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1038/nm.3052","ISBN":"1546-170X (Electronic)\\n1078-8956 (Linking)","ISSN":"10788956","PMID":"23314056","abstract":"Here we introduce tethered capsule endomicroscopy, which involves swallowing an optomechanically engineered pill that captures cross-sectional microscopic images of the gut wall at 30 μm (lateral) × 7 μm (axial) resolution as it travels through the digestive tract. 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We demonstrate a high speed, two-dimensional (2D) distal scanning capsule with a micromotor for fast rotary scanning and a pneumatic actuator for precision longitudinal scanning. Longitudinal position measurement and image registration were performed by optical tracking of the pneumatic scanner. The 2D scanning device enables high resolution imaging over a small field of view and is suitable for OCT as well as other scanning microscopies. Large field of view imaging for screening or surveillance applications can also be achieved by proximally pulling back or advancing the capsule while scanning the distal high-speed micromotor. Circumferential en face OCT was demonstrated in living swine at 250 Hz frame rate and 1 MHz A-scan rate using a MEMS tunable VCSEL light source at 1300 nm. Cross-sectional and en face OCT views of the upper and lower gastrointestinal tract were generated with precision distal pneumatic longitudinal actuation as well as proximal manual longitudinal actuation. These devices could enable clinical studies either as an adjunct to endoscopy, attached to an endoscope, or as a swallowed tethered capsule for non-endoscopic imaging without sedation. The combination of ultrahigh speed imaging and distal scanning capsule technology could enable both screening and surveillance applications.","author":[{"dropping-particle":"","family":"Liang","given":"Kaicheng","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Traverso","given":"Giovanni","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lee","given":"Hsiang-Chieh","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ahsen","given":"Osman Oguz","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wang","given":"Zhao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Potsaid","given":"Benjamin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Giacomelli","given":"Michael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jayaraman","given":"Vijaysekhar","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Barman","given":"Ross","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cable","given":"Alex","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mashimo","given":"Hiroshi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Langer","given":"Robert","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fujimoto","given":"James G.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Biomedical Optics Express","id":"ITEM-3","issue":"4","issued":{"date-parts":[["2015","4","1"]]},"page":"1146","title":"Ultrahigh speed en face OCT capsule for endoscopic imaging","type":"article-journal","volume":"6"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>4,98,99</sup>","plainTextFormattedCitation":"4,98,99","previouslyFormattedCitation":"<sup>4,98,99</sup>"},"properties":{"noteIndex":0},"schema":""}4,98,99. Another area of research opened up by the utilization of sensor technology is computer aided diagnosis (CADx) that promises to automate the identification and interpretation of pathologyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1055/s-0043-109430","ISSN":"0013-726X","author":[{"dropping-particle":"","family":"Mori","given":"Yuichi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kudo","given":"Shin-ei","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Berzin","given":"Tyler","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Misawa","given":"Masashi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Takeda","given":"Kenichi","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Endoscopy","id":"ITEM-1","issue":"08","issued":{"date-parts":[["2017","8","24"]]},"page":"813-819","title":"Computer-aided diagnosis for colonoscopy","type":"article-journal","volume":"49"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1016/j.gie.2016.07.045","ISSN":"00165107","author":[{"dropping-particle":"","family":"Leggett","given":"Cadman L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wang","given":"Kenneth K.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastrointestinal Endoscopy","id":"ITEM-2","issue":"5","issued":{"date-parts":[["2016","11"]]},"page":"842-844","title":"Computer-aided diagnosis in GI endoscopy: looking into the future","type":"article-journal","volume":"84"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>166,167</sup>","plainTextFormattedCitation":"166,167","previouslyFormattedCitation":"<sup>167,168</sup>"},"properties":{"noteIndex":0},"schema":""}166,167. Though these two technologies have demonstrated promising results in laboratory and pre-clinical studies but they are still in their infancy and further work is required to assess the accuracy, sensitivity and specificity of these techniques in CE before they gain wider clinical acceptance.A technical challenge unique to CE is localization. Currently, commercially available CE devices are passively moved through the GI tract by peristaltic forces and there is no way for the clinician is unable to control the motion of or to stop thethe capsule or position if an area of interest is observed. The location of the capsule at these sites relative to some known frame of reference is required to enable further treatment or to follow-up with additional observations. Localization of the capsule is the subject of much research in CE, and the following section gives a brief overview of the advantages and disadvantages of some of the methods used. [H2]Virtual biopsy Histological evaluation of tissue obtained from biopsy is a vital part of medical diagnosis. Biopsies can be performed routinely during routine endoscopy through integrated interventional channels. However, capsules are hindered by limited payload capacity, unstable positioning and imprecise capsule/pathology localization that thwarts tissue biopsy for subsequent histological analysis. An alternative method to analysze tissue and achieve the same goal as histopathology that could be integrated into future CE devices is virtual biopsy. Theoretical advantages of this method include decreased risk of biopsy-induced adverse events, faster diagnosis and the potential for reduced costs owing to the absence of further tissue processing and pathologic reviewADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.gie.2013.07.035","ISSN":"00165107","PMID":"24342587","author":[{"dropping-particle":"","family":"Deutsch","given":"John C.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastrointestinal Endoscopy","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2014"]]},"page":"64-65","publisher":"Elsevier Ltd","title":"The optical biopsy of small gastric lesions","type":"article-journal","volume":"79"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1109/JPROC.2010.2041830","ISSN":"00189219","author":[{"dropping-particle":"","family":"Kang","given":"J. 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However, these advantages may be offset by the cost associated with increased surveillance frequency, missed detection of a malignant processADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.gie.2013.07.035","ISSN":"00165107","PMID":"24342587","author":[{"dropping-particle":"","family":"Deutsch","given":"John C.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastrointestinal Endoscopy","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2014"]]},"page":"64-65","publisher":"Elsevier Ltd","title":"The optical biopsy of small gastric lesions","type":"article-journal","volume":"79"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>161</sup>","plainTextFormattedCitation":"161","previouslyFormattedCitation":"<sup>162</sup>"},"properties":{"noteIndex":0},"schema":""}161 and technical challenges such as limited telemetry bandwidth of wireless CE.Not all imaging modalities are suitable for virtual biopsy in CE. Suitable modalities must be able to acquire subsurface images of a resolution sufficient to view cellular structure within a timeframe of tens of millisecondsADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/JPROC.2010.2041830","ISSN":"00189219","author":[{"dropping-particle":"","family":"Kang","given":"J. U.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Proceedings of the IEEE","id":"ITEM-1","issue":"4","issued":{"date-parts":[["2010"]]},"page":"503-505","title":"Virtual biopsy","type":"article-journal","volume":"98"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>168</sup>","plainTextFormattedCitation":"168","previouslyFormattedCitation":"<sup>169</sup>"},"properties":{"noteIndex":0},"schema":""}168 to avoid motion artifacts due to respiration or other causes. This precludes modalities such as WLI CE, as well as chromoendoscopy, endomicroscopy, endocytoscopy as they are limited by the maximum depth of light penetration around of ~ 50 ?mADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/j.1365-2036.2011.04647.x","ISBN":"1365-2036 (Electronic)\\r0269-2813 (Linking)","ISSN":"02692813","PMID":"21457290","abstract":"Endocytoscopy (EC) enables in vivo microscopic imaging at 1400-fold magnification, thereby allowing the analysis of mucosal structures at the cellular level. In contrast to fluorescence imaging with confocal laser endomicroscopy which allows analysis of mucosal structures up to 250 μm in depth, EC is based on the principle of contact light microscopy and only allows visualisation of the very superficial mucosal layer.","author":[{"dropping-particle":"","family":"Neumann","given":"H.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fuchs","given":"F. 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Of these OCT and ?US have been utilised in CEADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/TBME.2018.2852715","ISSN":"0018-9294","author":[{"dropping-particle":"","family":"Lay","given":"Holly","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cummins","given":"Gerard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cox","given":"Benjamin F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Qiu","given":"Yongqiang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Turcanu","given":"Mihnea Vlad","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"McPhillips","given":"Rachael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Connor","given":"Ciaran","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gregson","given":"Rachael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Clutton","given":"Eddie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Desmulliez","given":"Marc P.Y.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cochran","given":"Sandy","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Transactions on Biomedical Engineering","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2018"]]},"page":"632 - 639","title":"In-Vivo Evaluation of Microultrasound and Thermometric Capsule Endoscopes","type":"article-journal","volume":"66"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1038/nm.3052","ISBN":"1546-170X (Electronic)\\n1078-8956 (Linking)","ISSN":"10788956","PMID":"23314056","abstract":"Here we introduce tethered capsule endomicroscopy, which involves swallowing an optomechanically engineered pill that captures cross-sectional microscopic images of the gut wall at 30 μm (lateral) × 7 μm (axial) resolution as it travels through the digestive tract. 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We demonstrate a high speed, two-dimensional (2D) distal scanning capsule with a micromotor for fast rotary scanning and a pneumatic actuator for precision longitudinal scanning. Longitudinal position measurement and image registration were performed by optical tracking of the pneumatic scanner. The 2D scanning device enables high resolution imaging over a small field of view and is suitable for OCT as well as other scanning microscopies. Large field of view imaging for screening or surveillance applications can also be achieved by proximally pulling back or advancing the capsule while scanning the distal high-speed micromotor. Circumferential en face OCT was demonstrated in living swine at 250 Hz frame rate and 1 MHz A-scan rate using a MEMS tunable VCSEL light source at 1300 nm. Cross-sectional and en face OCT views of the upper and lower gastrointestinal tract were generated with precision distal pneumatic longitudinal actuation as well as proximal manual longitudinal actuation. These devices could enable clinical studies either as an adjunct to endoscopy, attached to an endoscope, or as a swallowed tethered capsule for non-endoscopic imaging without sedation. The combination of ultrahigh speed imaging and distal scanning capsule technology could enable both screening and surveillance applications.","author":[{"dropping-particle":"","family":"Liang","given":"Kaicheng","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Traverso","given":"Giovanni","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lee","given":"Hsiang-Chieh","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ahsen","given":"Osman Oguz","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wang","given":"Zhao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Potsaid","given":"Benjamin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Giacomelli","given":"Michael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jayaraman","given":"Vijaysekhar","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Barman","given":"Ross","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cable","given":"Alex","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mashimo","given":"Hiroshi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Langer","given":"Robert","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fujimoto","given":"James G.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Biomedical Optics Express","id":"ITEM-3","issue":"4","issued":{"date-parts":[["2015","4","1"]]},"page":"1146","title":"Ultrahigh speed en face OCT capsule for endoscopic imaging","type":"article-journal","volume":"6"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>4,98,99</sup>","plainTextFormattedCitation":"4,98,99","previouslyFormattedCitation":"<sup>4,98,99</sup>"},"properties":{"noteIndex":0},"schema":""}4,98,99 . Examples of images obtained with OCT and ?US are shown in REF _Ref536629657 \h Fig. 2. OCT is an attractive imaging technology for this application as it is capable of rapid volumetric imaging of mucosal and submucosal structures of the esophagusoesophagus in microscopic detail (axial resolution: ~10 ?m, lateral resolution: ~30?m) and has been successfully demonstrated in ex vivo and in vivo trialsADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1038/nm.3052","ISBN":"1546-170X (Electronic)\\n1078-8956 (Linking)","ISSN":"10788956","PMID":"23314056","abstract":"Here we introduce tethered capsule endomicroscopy, which involves swallowing an optomechanically engineered pill that captures cross-sectional microscopic images of the gut wall at 30 μm (lateral) × 7 μm (axial) resolution as it travels through the digestive tract. Results in human subjects show that this technique rapidly provides three-dimensional, microstructural images of the upper gastrointestinal tract in a simple and painless procedure, opening up new opportunities for screening for internal diseases.","author":[{"dropping-particle":"","family":"Gora","given":"Michalina J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sauk","given":"Jenny S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Carruth","given":"Robert W.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gallagher","given":"Kevin A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Suter","given":"Melissa J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nishioka","given":"Norman S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kava","given":"Lauren E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rosenberg","given":"Mireille","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bouma","given":"Brett E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tearney","given":"Guillermo J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Nature Medicine","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2013","2","13"]]},"page":"238-240","title":"Tethered capsule endomicroscopy enables less invasive imaging of gastrointestinal tract microstructure","type":"article-journal","volume":"19"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1038/s41598-018-20668-8","ISSN":"2045-2322","author":[{"dropping-particle":"","family":"Tabatabaei","given":"Nima","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kang","given":"DongKyun","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kim","given":"Minkyu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wu","given":"Tao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Grant","given":"Catriona N.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rosenberg","given":"Mireille","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nishioka","given":"Norman S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hesterberg","given":"Paul E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Garber","given":"John","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yuan","given":"Qian","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Katz","given":"Aubrey J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tearney","given":"Guillermo J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Scientific Reports","id":"ITEM-2","issue":"1","issued":{"date-parts":[["2018","12","8"]]},"page":"2631","title":"Clinical Translation of Tethered Confocal Microscopy Capsule for Unsedated Diagnosis of Eosinophilic Esophagitis","type":"article-journal","volume":"8"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.3390/diagnostics4020057","ISSN":"2075-4418","author":[{"dropping-particle":"","family":"Tsai","given":"Tsung-Han","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fujimoto","given":"James","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mashimo","given":"Hiroshi","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Diagnostics","id":"ITEM-3","issue":"2","issued":{"date-parts":[["2014","5","5"]]},"page":"57-93","title":"Endoscopic Optical Coherence Tomography for Clinical Gastroenterology","type":"article-journal","volume":"4"},"uris":[""]},{"id":"ITEM-4","itemData":{"DOI":"10.1002/jbio.200710017","ISBN":"1864-063X","ISSN":"1864063X","PMID":"19343643","abstract":"In the current paper we present results of application of endoscopic time-domain OCT (EOCT) with lateral scanning by forward looking miniprobe. We analysed material of clinical studies of 554 patients: 164 patients with urinary bladder pathology, and 390 with gastrointestinal tract pathology. We reviewed the materials obtained in different clinics using the OCT device elaborated at the Institute of Applied Physics. We demonstrate results of EOCT application in detection of early cancer and surgery guidance, examples of combined use of OCT and fluorescence imaging. As a result, we show the diagnostic accuracy of EOCT in specific clinical tasks. The sensitivity of EOCT cancer determination in Barrett's esophagus is from 71% to 85% at different stages of neoplasia with specificity 68% for all stages. As for bladder carcinoma, the sensitivity and specificity are 85% and 68%, respectively. In colon dysplasia EOST demonstrates high efficacy: sensitivity 92% and specificity 84%.","author":[{"dropping-particle":"","family":"Zagaynova","given":"E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gladkova","given":"N.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shakhova","given":"N.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gelikonov","given":"G.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gelikonov","given":"V.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Biophotonics","id":"ITEM-4","issue":"2","issued":{"date-parts":[["2008"]]},"page":"114-128","title":"Endoscopic OCT with forward-looking probe: Clinical studies in urology and gastroenterology","type":"article-journal","volume":"1"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>91,98,170,171</sup>","plainTextFormattedCitation":"91,98,170,171","previouslyFormattedCitation":"<sup>91,98,171,172</sup>"},"properties":{"noteIndex":0},"schema":""}91,98,170,171. Various studies using OCT with conventional endoscopy have demonstrated high-resolution volumetric images comparable to those obtained from histology. Furthermore, an accuracy of 92.7%, was reported for the detection of esophagealoesophageal carcinomaADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.gie.2009.11.052","ISSN":"00165107","author":[{"dropping-particle":"","family":"Hatta","given":"Waku","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Uno","given":"Kaname","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Koike","given":"Tomoyuki","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yokosawa","given":"Satoshi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Iijima","given":"Katsunori","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Imatani","given":"Akira","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shimosegawa","given":"Tooru","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastrointestinal Endoscopy","id":"ITEM-1","issue":"6","issued":{"date-parts":[["2010","5"]]},"page":"899-906","title":"Optical coherence tomography for the staging of tumor infiltration in superficial esophageal squamous cell carcinoma","type":"article-journal","volume":"71"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>172</sup>","plainTextFormattedCitation":"172","previouslyFormattedCitation":"<sup>173</sup>"},"properties":{"noteIndex":0},"schema":""}172 and a study of 33 patients with Barrett’s esophagusoesophagus demonstrated accuracy, sensitivity and specificity of 78%, 68% and 82% respectively was reported for the detection of dysplasiaADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.gie.2005.07.048","ISSN":"00165107","author":[{"dropping-particle":"","family":"Isenberg","given":"Gerard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"V.","family":"Sivak","given":"Michael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chak","given":"Amitabh","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wong","given":"Richard C.K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Willis","given":"Joseph E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wolf","given":"Brian","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rowland","given":"Douglas Y.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Das","given":"Ananya","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rollins","given":"Andrew","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastrointestinal Endoscopy","id":"ITEM-1","issue":"6","issued":{"date-parts":[["2005","12"]]},"page":"825-831","title":"Accuracy of endoscopic optical coherence tomography in the detection of dysplasia in Barrett's esophagus: a prospective, double-blinded study","type":"article-journal","volume":"62"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>173</sup>","plainTextFormattedCitation":"173","previouslyFormattedCitation":"<sup>174</sup>"},"properties":{"noteIndex":0},"schema":""}173. Initial demonstrations of OCT in CE have thus shown its potential in differentiating between healthy and abnormal tissueADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1038/nm.3052","ISBN":"1546-170X (Electronic)\\n1078-8956 (Linking)","ISSN":"10788956","PMID":"23314056","abstract":"Here we introduce tethered capsule endomicroscopy, which involves swallowing an optomechanically engineered pill that captures cross-sectional microscopic images of the gut wall at 30 μm (lateral) × 7 μm (axial) resolution as it travels through the digestive tract. Results in human subjects show that this technique rapidly provides three-dimensional, microstructural images of the upper gastrointestinal tract in a simple and painless procedure, opening up new opportunities for screening for internal diseases.","author":[{"dropping-particle":"","family":"Gora","given":"Michalina J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sauk","given":"Jenny S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Carruth","given":"Robert W.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gallagher","given":"Kevin A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Suter","given":"Melissa J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nishioka","given":"Norman S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kava","given":"Lauren E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rosenberg","given":"Mireille","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bouma","given":"Brett E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tearney","given":"Guillermo J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Nature Medicine","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2013","2","13"]]},"page":"238-240","title":"Tethered capsule endomicroscopy enables less invasive imaging of gastrointestinal tract microstructure","type":"article-journal","volume":"19"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>98</sup>","plainTextFormattedCitation":"98","previouslyFormattedCitation":"<sup>98</sup>"},"properties":{"noteIndex":0},"schema":""}98. However, many of the current OCT CE devices require further integration and miniaturization to remove the tether to the external illumination source before this technology can be used to image the entire GI tract. Confocal laser endomicroscopy is slower because it can acquire only one image at a time as it scans through various focal depths, and is therefore not suitable for CEADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.gie.2014.06.021","ISBN":"1097-6779","ISSN":"10976779","PMID":"25442092","abstract":"CLE is an emerging technology that has the potential to significantly reduce the number of biopsies in BE and IBD and reduce the need for removal of non-neoplastic colorectal polyps compared with WLE. In the bile duct and within pancreatic cysts, it can provide surrogate real-time histological information that has previously been unavailable. Limitations of CLE include the high cost of the equipment and probes, the lack of proven efficacy compared with other widely available advanced imaging techniques, and the need for either intravenous or topical fluorescent ontrast agents. Before the technology can be widely accepted, many further studies are needed to determine its clinical efficacy and evaluate its cost-effectiveness and its utilization in both academic and community settings.","author":[{"dropping-particle":"","family":"Chauhan","given":"Shailendra S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Abu Dayyeh","given":"Barham K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bhat","given":"Yasser M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gottlieb","given":"Klaus T.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hwang","given":"Joo Ha","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Komanduri","given":"Sri","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Konda","given":"Vani","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lo","given":"Simon K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Manfredi","given":"Michael A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Maple","given":"John T.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Murad","given":"Faris M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Siddiqui","given":"Uzma D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Banerjee","given":"Subhas","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wallace","given":"Michael B.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastrointestinal Endoscopy","id":"ITEM-1","issue":"6","issued":{"date-parts":[["2014"]]},"page":"928-938","title":"Confocal laser endomicroscopy","type":"article-journal","volume":"80"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>174</sup>","plainTextFormattedCitation":"174","previouslyFormattedCitation":"<sup>175</sup>"},"properties":{"noteIndex":0},"schema":""}174. Moreover, it has a small field of view, making it impractical to screen large areas of the bowel, and requires exogenous fluorescent markers to ensure good sensitivityADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.3390/diagnostics4020057","ISSN":"2075-4418","author":[{"dropping-particle":"","family":"Tsai","given":"Tsung-Han","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fujimoto","given":"James","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mashimo","given":"Hiroshi","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Diagnostics","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2014","5","5"]]},"page":"57-93","title":"Endoscopic Optical Coherence Tomography for Clinical Gastroenterology","type":"article-journal","volume":"4"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>91</sup>","plainTextFormattedCitation":"91","previouslyFormattedCitation":"<sup>91</sup>"},"properties":{"noteIndex":0},"schema":""}91 and has not been currently miniaturised for use in CE. As previously noted, ?US can image mucosal and transmural pathology, which might enhance its use for virtual biopsy when combined with other diagnostic modalitiesADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1186/1746-1596-7-98","ISBN":"1746-1596 (Electronic)\\n1746-1596 (Linking)","ISSN":"1746-1596","PMID":"22889003","abstract":"UNLABELLED: Epithelial cancers account for substantial mortality and are an important public health concern. With the need for earlier detection and treatment of these malignancies, the ability to accurately detect precancerous lesions has an increasingly important role in controlling cancer incidence and mortality. New optical technologies are capable of identifying early pathology in tissues or organs in which cancer is known to develop through stages of dysplasia, including the esophagus, colon, pancreas, liver, bladder, and cervix. These diagnostic imaging advances, together as a field known as optical endomicroscopy, are based on confocal microscopy, spectroscopy-based imaging, and optical coherence tomography (OCT), and function as \"optical biopsies,\" enabling tissue pathology to be imaged in situ and in real time without the need to excise and process specimens as in conventional biopsy and histopathology. Optical biopsy techniques can acquire high-resolution, cross-sectional images of tissue structure on the micron scale through the use of endoscopes, catheters, laparoscopes, and needles. Since the inception of these technologies, dramatic technological advances in accuracy, speed, and functionality have been realized. The current paradigm of optical biopsy, or single-area, point-based images, is slowly shifting to more comprehensive microscopy of larger tracts of mucosa. With the development of Fourier-domain OCT, also known as optical frequency domain imaging or, more recently, volumetric laser endomicroscopy, comprehensive surveillance of the entire distal esophagus is now achievable at speeds that were not possible with conventional OCT technologies. Optical diagnostic technologies are emerging as clinically useful tools with the potential to set a new standard for real-time diagnosis. New imaging techniques enable visualization of high-resolution, cross-sectional images and offer the opportunity to guide biopsy, allowing maximal diagnostic yields and appropriate staging without the limitations and risks inherent with current random biopsy protocols. However, the ability of these techniques to achieve widespread adoption in clinical practice depends on future research designed to improve accuracy and allow real-time data transmission and storage, thereby linking pathology to the treating physician. These imaging advances are expected to eventually offer a see-and-treat paradigm, leading to improved patient care and potential cost reduction.\\…","author":[{"dropping-particle":"","family":"Carignan","given":"Charles S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yagi","given":"Yukako","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Diagnostic Pathology","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2012","1"]]},"page":"98","title":"Optical endomicroscopy and the road to real-time, in vivo pathology: present and future","type":"article-journal","volume":"7"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>175</sup>","plainTextFormattedCitation":"175","previouslyFormattedCitation":"<sup>176</sup>"},"properties":{"noteIndex":0},"schema":""}175. This modality has been achieved used in conventional endoscopy through the use of fragile mini-probes that can be inserted into the biopsy channel. These mini-probes can reach frequencies only as high as 30MHz but results of clinical trials have demonstrated the successfully detection of Barrett’s esophagusoesophagusADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/S0016-5107(97)70063-4","ISSN":"00165107","author":[{"dropping-particle":"","family":"Adrain","given":"Alyn L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ter","given":"Han-Chuan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cassidy","given":"Michael J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schiano","given":"Thomas D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Liu","given":"Ji-Bin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Miller","given":"Larry S.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastrointestinal Endoscopy","id":"ITEM-1","issue":"2","issued":{"date-parts":[["1997","8"]]},"page":"147-151","title":"High-resolution endoluminal sonography is a sensitive modality for the identification of Barrett's metaplasia","type":"article-journal","volume":"46"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>176</sup>","plainTextFormattedCitation":"176","previouslyFormattedCitation":"<sup>177</sup>"},"properties":{"noteIndex":0},"schema":""}176, esophagealoesophageal cancerADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/S0016-5107(96)70224-9","ISSN":"00165107","author":[{"dropping-particle":"","family":"Murata","given":"Yoko","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Suzuki","given":"Shigeru","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ohta","given":"Masao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mitsunaga","given":"Atsushi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hayashi","given":"Kazuhiko","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yoshida","given":"Kazunari","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ide","given":"Hiroko","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastrointestinal Endoscopy","id":"ITEM-1","issue":"1","issued":{"date-parts":[["1996","7"]]},"page":"23-28","title":"Small ultrasonic probes for determination of the depth of superficial esophageal cancer","type":"article-journal","volume":"44"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>177</sup>","plainTextFormattedCitation":"177","previouslyFormattedCitation":"<sup>178</sup>"},"properties":{"noteIndex":0},"schema":""}177 and colorectal tumoursADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/codi.12445","ISBN":"1462-8910","ISSN":"14628910","abstract":"Aim: With an increasing array of treatment modalities available for colon cancer, it is increasingly important to stage tumours accurately to allocate the appropriate management. This study evaluated the accuracy of mini-probe endoscopic ultrasound (EUS) in assigning clinical stage to colon cancer. Method: An electronic search was performed in January 2013 using the Embase, MEDLINE and Cochrane databases. This was supplemented by a hand search of published abstracts from scientific meetings. Trials evaluating the accuracy of the mini-probe EUS compared with histopathological grade in determining the clinical stage of colon cancer were included in this pooled analysis. The main outcome measures included accuracy, sensitivity and specificity for T and N staging. Results: Ten studies were identified which compared the mini-probe EUS staging of 642 colon or rectal cancers with the histopathological specimen. The pooled sensitivity and specificity for staging were 0.91 and 0.98 for T1 tumours, 0.78 and 0.94 for T2 tumours, 0.97 and 0.90 for T3/T4 tumours and 0.63 and 0.82 for nodal staging. Eight per cent of T1/T2 tumours were upstaged to T3/T4 tumours and 5% of T3/T4 tumours were downstaged. Conclusion: Mini-probe EUS is highly effective for assigning clinical stage in colon cancer and in identifying patients who may be suitable for nonsurgical treatment including neoadjuvant chemotherapy or endoscopic resection. ? 2013 The Association of Coloproctology of Great Britain and Ireland.","author":[{"dropping-particle":"","family":"Gall","given":"T. M. H.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Markar","given":"S. 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Initial development of ?US CE has shown good agreement between the ultrasound image and histologyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/TBME.2018.2852715","ISSN":"0018-9294","author":[{"dropping-particle":"","family":"Lay","given":"Holly","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cummins","given":"Gerard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cox","given":"Benjamin F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Qiu","given":"Yongqiang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Turcanu","given":"Mihnea Vlad","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"McPhillips","given":"Rachael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Connor","given":"Ciaran","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gregson","given":"Rachael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Clutton","given":"Eddie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Desmulliez","given":"Marc P.Y.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cochran","given":"Sandy","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Transactions on Biomedical Engineering","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2018"]]},"page":"632 - 639","title":"In-Vivo Evaluation of Microultrasound and Thermometric Capsule Endoscopes","type":"article-journal","volume":"66"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>4</sup>","plainTextFormattedCitation":"4","previouslyFormattedCitation":"<sup>4</sup>"},"properties":{"noteIndex":0},"schema":""}4 but further work is needed to verify whether ?US CE can achieve comparable or superior performance consistently.Virtual biopsy has been proposed to replace histology in many settingsADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/j.1440-1746.2008.05469.x","ISBN":"1440-1746 (Electronic)\n0815-9319 (Linking)","ISSN":"14401746","PMID":"18761561","abstract":"Confocal endomicroscopy (CEM) is a recent advancement in imaging technology that incorporates a confocal laser microscope into the tip of a flexible endoscope. The 1000-fold magnification and high resolution allows for real time in vivo histology or \"virtual biopsies\" of the gastrointestinal tract mucosa. CEM has the capability to instantaneously diagnose intra-epithelial neoplasia during endoscopy, alone or in combination with a \"red-flag\" technique, such as chromoendoscopy. Therefore, there is clinical utility in the surveillance or diagnosis of Barrett's esophagus, gastric intestinal metaplasia and cancer, longstanding ulcerative colitis, and colonic neoplasia. Furthermore, CEM also appears to be useful in the evaluation of coeliac disease, microscopic colitis, and in diagnosing Helicobacter pylori chronic gastritis. This review examines the current available data on the utility of this new technology in clinical gastroenterology and its potential impact in the future.","author":[{"dropping-particle":"","family":"Nguyen","given":"Nam Q.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leong","given":"Rupert W L","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Gastroenterology and Hepatology (Australia)","id":"ITEM-1","issue":"10","issued":{"date-parts":[["2008"]]},"page":"1483-1491","title":"Current application of confocal endomicroscopy in gastrointestinal disorders","type":"article-journal","volume":"23"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1038/nrgastro.2017.147","ISSN":"17595053","PMID":"29139480","abstract":"? 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. Environmental enteric dysfunction (EED) is a disease of the small intestine affecting children and adults in low and middle income countries. Arising as a consequence of repeated infections, gut inflammation results in impaired intestinal absorptive and barrier function, leading-to poor nutrient uptake and ultimately to stunting and other developmental limitations. Progress-towards new biomarkers and interventions for EED is hampered by the practical and'ethical difficulties of cross-validation with the gold standard of biopsy and histology. Optical'biopsy techniques ' which can provide minimally invasive or noninvasive alternatives to'biopsy' could offer other routes to validation and could potentially be used as point?of?care tests among the general population. This Consensus Statement identifies and reviews the most promising candidate optical biopsy technologies for applications in EED, critically assesses them against criteria identified for successful deployment in developing world settings, and proposes further lines of enquiry. Importantly, many of the techniques discussed could also be adapted to monitor the impaired intestinal barrier in other settings such as IBD, autoimmune enteropathies, coeliac disease, graft-versus-host disease, small intestinal transplantation or critical care.","author":[{"dropping-particle":"","family":"Thompson","given":"Alex J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hughes","given":"Michael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Anastasova","given":"Salzitsa","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Conklin","given":"Laurie S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Thomas","given":"Tudor","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leggett","given":"Cadman","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Faubion","given":"William A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Miller","given":"Thomas J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Delaney","given":"Peter","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lacombe","given":"Fran?ois","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Loiseau","given":"Sacha","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Meining","given":"Alexander","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Richards-Kortum","given":"Rebecca","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tearney","given":"Guillermo J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kelly","given":"Paul","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yang","given":"Guang Zhong","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Nature Reviews Gastroenterology and Hepatology","id":"ITEM-2","issued":{"date-parts":[["2017"]]},"title":"The potential role of optical biopsy in the study and diagnosis of environmental enteric dysfunction","type":"article"},"uris":["",""]},{"id":"ITEM-3","itemData":{"DOI":"10.21037/atm.2017.04.21","ISSN":"23055839","abstract":"Video capsule endoscopy (VCE) has been of immense benefit in the diagnosis and management of gastrointestinal (GI) disorders since its introduction in 2001. However, it suffers from a number of well recognized deficiencies. Amongst these is the limited capability of white light imaging, which is restricted to analysis of the mucosal surface. Current capsule endoscopes are dependent on visual manifestation of disease and limited in regards to transmural imaging and detection of deeper pathology. Ultrasound capsule endoscopy (USCE) has the potential to overcome surface only imaging and provide transmural scans of the GI tract. The integration of high frequency microultrasound (?US) into capsule endoscopy would allow high resolution transmural images and provide a means of both qualitative and quantitative assessment of the bowel wall. Quantitative ultrasound (QUS) can provide data in an objective and measurable manner, potentially reducing lengthy interpretation times by incorporation into an automated diagnostic process. The research described here is focused on the development of USCE and other complementary diagnostic and therapeutic modalities. Presently investigations have entered a preclinical phase with laboratory investigations running concurrently.","author":[{"dropping-particle":"","family":"Cox","given":"Benjamin F. B.F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stewart","given":"Fraser","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lay","given":"Holly","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cummins","given":"Gerard","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Newton","given":"I.P. Ian P.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Desmulliez","given":"Marc P. Y. M.P. Y.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Steele","given":"R.J. C. Robert J. C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nthke?","given":"I.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cochran","given":"Sandy","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"N?thke","given":"Inke","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cochran","given":"Sandy","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Annals of Translational Medicine","id":"ITEM-3","issue":"9","issued":{"date-parts":[["2017","5"]]},"page":"201-201","title":"Ultrasound capsule endoscopy: sounding out the future","type":"article-journal","volume":"5"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>3,178,179</sup>","plainTextFormattedCitation":"3,178,179","previouslyFormattedCitation":"<sup>3,179,180</sup>"},"properties":{"noteIndex":0},"schema":""}3,178,179 when endoscopic imaging technology matures and proficiency with these tools has increased. However, for this to be the case, high accuracy achievable with virtual biopsy methods must be established. In many of the studies published to date, the sensitivities and specificities of virtual biopsy techniques using conventional endoscopy are respectively within 90.0% and 83.3% respectively for distinguishing Crohn’s disease from ulcerative colitis using OCTADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"ISSN":"1542-3565","PMID":"15625653","abstract":"BACKGROUND & AIMS Transmural inflammation, a distinguishing feature of Crohn's disease (CD), cannot be assessed by conventional colonoscopy with mucosal biopsy. Our previous ex vivo study of histology-correlated optical coherence tomography (OCT) imaging on colectomy specimens of CD and ulcerative colitis (UC) showed that disruption of the layered structure of colon wall on OCT is an accurate marker for transmural inflammation of CD. We performed an in vivo colonoscopic OCT in patients with a clinical diagnosis of CD or UC using the previously established, histology-correlated OCT imaging criterion. METHODS OCT was performed in 40 patients with CD (309 images) and 30 patients with UC (292 images). Corresponding endoscopic features of mucosal inflammation were documented. Two gastroenterologists blinded to endoscopic and clinical data scored the OCT images independently to assess the feature of disrupted layered structure. RESULTS Thirty-six CD patients (90.0%) had disrupted layered structure, whereas 5 UC patients (16.7%) had disrupted layered structure (P < .001). Using the clinical diagnosis of CD or UC as the gold standard, the disrupted layered structure on OCT indicative of transmural inflammation had a diagnostic sensitivity and specificity of 90.0% (95% CI: 78.0%, 96.5%) and 83.3% (95% CI: 67.3%, 93.3%) for CD, respectively. The kappa coefficient in the interpretation of OCT images was 0.80 (95% CI: 0.75, 0.86, P < .001). CONCLUSIONS In vivo colonoscopic OCT is feasible and accurate to detect disrupted layered structure of the colon wall indicative of transmural inflammation, providing a valuable tool to distinguish CD from UC.","author":[{"dropping-particle":"","family":"Shen","given":"Bo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zuccaro","given":"Gregory","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gramlich","given":"Terry L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gladkova","given":"Natalie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Trolli","given":"Patricia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kareta","given":"Margaret","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Delaney","given":"Conor P","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Connor","given":"Jason T","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lashner","given":"Bret A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bevins","given":"Charles L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Feldchtein","given":"Felix","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Remzi","given":"Feza H","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bambrick","given":"Marlene L","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fazio","given":"Victor W","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association","id":"ITEM-1","issue":"12","issued":{"date-parts":[["2004","12"]]},"page":"1080-7","title":"In vivo colonoscopic optical coherence tomography for transmural inflammation in inflammatory bowel disease.","type":"article-journal","volume":"2"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>95</sup>","plainTextFormattedCitation":"95","previouslyFormattedCitation":"<sup>95</sup>"},"properties":{"noteIndex":0},"schema":""}95 and within 80 – 90% for the detection of lesionsADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1053/j.gastro.2011.04.027","ISBN":"1528-0012 (Electronic)\\r0016-5085 (Linking)","ISSN":"00165085","PMID":"21521641","author":[{"dropping-particle":"","family":"Roy","given":"Hemant K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Goldberg","given":"Michael J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bajaj","given":"Shailesh","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Backman","given":"Vadim","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastroenterology","id":"ITEM-1","issue":"7","issued":{"date-parts":[["2011"]]},"page":"1863-1867","title":"Colonoscopy and optical biopsy: Bridging technological advances to clinical practice","type":"article-journal","volume":"140"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>180</sup>","plainTextFormattedCitation":"180","previouslyFormattedCitation":"<sup>181</sup>"},"properties":{"noteIndex":0},"schema":""}180. In the latter case, whether such performance is acceptable owing to the risk of cancer development if lesions are missed, is unclear. Additionally, as most of the research on virtual biopsy to date has been done with conventional endoscopy, further work will be needed to verify whether these results are comparable with CE due to the mobile nature of the capsule as well as the effect of increased miniaturization and denser modality integration of the modalities on the system performance.[H2]Localization CE device localization is defined as knowledge of the position and orientation of the capsule with respect to either gastrointestinal tract anatomy and targets (internal localization) or to external reference systems such as antennas (external localization). This information is essential for accurate capsule navigation and to accurately and reliably map lesions and pathologies in the gastrointestinal tract with respect to internal or external frames of references for diagnosis, treatment and monitoringADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/TBME.2012.2201715","ISBN":"0018-9294 VO - 59","ISSN":"00189294","PMID":"22736628","abstract":"Obscure gastrointestinal (GI) bleeding, Crohn disease, Celiac disease, small bower tumors, and other disorders that occur in the GI tract have always been challenging to be diagnosed and treated due to the inevitable difficulty in accessing such a complex environment within the human body. With the invention of wireless capsule endoscope, the next generation of the traditional cabled endoscope, not only a dream has come true for the patients who have experienced a great discomfort and unpleasantness caused by the conventional endoscopic method, but also a new research field has been opened to develop a complete miniature robotic device that is swallowable and has full functions of diagnosis and treatment of the GI diseases. However, such an ideal device needs to be equipped with a highly accurate localization system to be able to exactly determine the location of lesions in the GI tract and provide essential feedback to an actuation mechanism controlling the device's movement. This paper presents a comprehensive overview of the localization systems for robotic endoscopic capsules, for which the motivation, challenges, and possible solutions of the proposed localization methods are also discussed.","author":[{"dropping-particle":"","family":"Than","given":"Trung Duc","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Alici","given":"Gursel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zhou","given":"Hao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Li","given":"Weihua","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Transactions on Biomedical Engineering","id":"ITEM-1","issue":"9","issued":{"date-parts":[["2012"]]},"page":"2387-2399","title":"A review of localization systems for robotic endoscopic capsules","type":"article-journal","volume":"59"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>181</sup>","plainTextFormattedCitation":"181","previouslyFormattedCitation":"<sup>182</sup>"},"properties":{"noteIndex":0},"schema":""}181,ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/JSEN.2016.2645945","ISSN":"1530-437X","abstract":"? 2016 IEEE. Wireless capsule endoscope (WCE) is a notable invention introduced in the biomedical industry. It involves swallowing a small disposable video capsule that takes photographic images as it passes through the gastrointestinal (GI) tract. WCE allows physicians to visualize and diagnose disorders covering the full length of the GI tract. Although WCE can provide useful images of the internal GI tract, the identification of the exact location of the detected disease remains unclear. Location information is very crucial for the subsequent treatment of the detected disease either through surgery or through local drug delivery. The huge potential of WCE in future endoscopic practice relies on the successful tracking of the wireless capsule. This paper presents a comprehensive systematic review on the recent developments in WCE loca lization techniques that have been reported in credible sources, namely, IEEE Xplore, PubMed, Scopus, Science Direct, Springer Link, and Google Scholar. Detailed analysis and systematic comparison are provided to highlight the achievement and future direction of WCE localization. This paper can be a valuable source of reference and guidance for future research in this field.","author":[{"dropping-particle":"","family":"Mateen","given":"Haris","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Basar","given":"Rubel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ahmed","given":"Afaz Uddin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ahmad","given":"Mohd Yazed","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Sensors Journal","id":"ITEM-1","issue":"5","issued":{"date-parts":[["2017","3","1"]]},"page":"1197-1206","title":"Localization of Wireless Capsule Endoscope: A Systematic Review","type":"article-journal","volume":"17"},"uris":["",""]}],"mendeley":{"formattedCitation":"<sup>182</sup>","plainTextFormattedCitation":"182","previouslyFormattedCitation":"<sup>183</sup>"},"properties":{"noteIndex":0},"schema":""}bining pathology detection and classification methodologies, such as the computer-aided diagnosisCADx methods discussed in the next section, along with internal and external CE localization not only enables repeated monitoring of the same disease sites but also assists accurate and reliable active locomotion of CE devices, mainly in the case of magnetically-driven, closed-loop navigation in non-rigid environments. The deformability of the gastrointestinal tract requires real-time knowledge of the pose of the capsule with respect to the surrounding unstructured environment, and vice versa. Thus, a hybrid approach, combining internal and external localization, together with autonomous or semi-autonomous detection (depending on the accuracy, sensitivity and specificity of the detection method) and classification of pathologies, is required for the next generation of active locomotion capsules and smart endoscopes. Autonomous or semi-autonomous detection of pathologies using CE prior to their internal or external localization, is mainly performed using embedded cameras with the support of advanced machine learning techniquesADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/S2468-1253(18)30282-6","ISSN":"24681253","author":[{"dropping-particle":"","family":"Ahmad","given":"Omer F","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Soares","given":"Antonio S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mazomenos","given":"Evangelos","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Brandao","given":"Patrick","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Vega","given":"Roser","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Seward","given":"Edward","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stoyanov","given":"Danail","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chand","given":"Manish","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lovat","given":"Laurence B","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"The Lancet Gastroenterology & Hepatology","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2019","1"]]},"page":"71-80","title":"Artificial intelligence and computer-aided diagnosis in colonoscopy: current evidence and future directions","type":"article-journal","volume":"4"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1142/S2424905X18400020","ISSN":"2424-905X","author":[{"dropping-particle":"","family":"Brandao","given":"Patrick","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zisimopoulos","given":"Odysseas","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mazomenos","given":"Evangelos","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ciuti","given":"Gastone","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bernal","given":"Jorge","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Visentini-Scarzanella","given":"Marco","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Menciassi","given":"Arianna","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dario","given":"Paolo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Koulaouzidis","given":"Anastasios","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Arezzo","given":"Alberto","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hawkes","given":"David J","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stoyanov","given":"Danail","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Medical Robotics Research","id":"ITEM-2","issue":"02","issued":{"date-parts":[["2018","6"]]},"page":"1840002","title":"Towards a Computed-Aided Diagnosis System in Colonoscopy: Automatic Polyp Segmentation Using Convolution Neural Networks","type":"article-journal","volume":"03"},"uris":["",""]}],"mendeley":{"formattedCitation":"<sup>183,184</sup>","plainTextFormattedCitation":"183,184","previouslyFormattedCitation":"<sup>184,185</sup>"},"properties":{"noteIndex":0},"schema":""}183,184. Embedding different sensing and imaging modalities into CE is very promising for both robotic control and diagnosis as these methods enable virtual reconstruction of the internal structure of the gastrointestinal tract, potentially improving localization accuracy.Internal localization of CE is performed mainly through optical imaging techniques, such as lumen reconstruction-based methodologies using sparse or dense depth-reconstruction techniquesADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1055/s-0043-121882","ISSN":"2364-3722","PMID":"29399619","abstract":"<p>Background and study aims?Capsule endoscopy (CE) is invaluable for minimally invasive endoscopy of the gastrointestinal tract; however, several technological limitations remain including lack of reliable lesion localization. We present an approach to 3D reconstruction and localization using visual information from 2D CE images.</p>","author":[{"dropping-particle":"","family":"Koulaouzidis","given":"Anastasios","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Iakovidis","given":"Dimitris","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yung","given":"Diana","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mazomenos","given":"Evangelos","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bianchi","given":"Federico","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Karagyris","given":"Alexandros","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dimas","given":"George","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stoyanov","given":"Danail","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Thorlacius","given":"Henrik","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Toth","given":"Ervin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ciuti","given":"Gastone","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Endoscopy International Open","id":"ITEM-1","issue":"02","issued":{"date-parts":[["2018","2"]]},"page":"E205-E210","title":"Novel experimental and software methods for image reconstruction and localization in capsule endoscopy","type":"article-journal","volume":"06"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>185</sup>","plainTextFormattedCitation":"185","previouslyFormattedCitation":"<sup>186</sup>"},"properties":{"noteIndex":0},"schema":""}185 or through structured light 3D scannersADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1055/a-0577-2798","ISSN":"2364-3722","abstract":"<p>Background and study aims?Polyp size measurement is an important diagnostic step during gastrointestinal endoscopy, and is mainly performed by visual inspection. However, lack of depth perception and objective reference points are acknowledged factors contributing to measurement errors in polyp size. In this paper, we describe the proof-of-concept of a polyp measurement device based on structured light technology for future endoscopes.</p>","author":[{"dropping-particle":"","family":"Visentini-Scarzanella","given":"Marco","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kawasaki","given":"Hiroshi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Furukawa","given":"Ryo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bonino","given":"Marco","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Arolfo","given":"Simone","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Secco","given":"Giacomo","non-dropping-particle":"Lo","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Arezzo","given":"Alberto","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Menciassi","given":"Arianna","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dario","given":"Paolo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ciuti","given":"Gastone","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Endoscopy International Open","id":"ITEM-1","issued":{"date-parts":[["2018"]]},"title":"A structured light laser probe for gastrointestinal polyp size measurement: a preliminary comparative study","type":"article-journal"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>186</sup>","plainTextFormattedCitation":"186","previouslyFormattedCitation":"<sup>187</sup>"},"properties":{"noteIndex":0},"schema":""}186. It is used primarily to aid navigation of CE, perform direct intervention on diseases and retarget pathological sites for subsequent treatment or follow up. Internal localization is often combined with external localization for computer-aided active capsule locomotion within laboratory prototypesADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1055/s-0043-121882","ISSN":"2364-3722","PMID":"29399619","abstract":"<p>Background and study aims?Capsule endoscopy (CE) is invaluable for minimally invasive endoscopy of the gastrointestinal tract; however, several technological limitations remain including lack of reliable lesion localization. We present an approach to 3D reconstruction and localization using visual information from 2D CE images.</p>","author":[{"dropping-particle":"","family":"Koulaouzidis","given":"Anastasios","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Iakovidis","given":"Dimitris","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yung","given":"Diana","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mazomenos","given":"Evangelos","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bianchi","given":"Federico","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Karagyris","given":"Alexandros","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dimas","given":"George","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stoyanov","given":"Danail","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Thorlacius","given":"Henrik","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Toth","given":"Ervin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ciuti","given":"Gastone","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Endoscopy International Open","id":"ITEM-1","issue":"02","issued":{"date-parts":[["2018","2"]]},"page":"E205-E210","title":"Novel experimental and software methods for image reconstruction and localization in capsule endoscopy","type":"article-journal","volume":"06"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1088/1361-6501/aa7ebf","ISSN":"0957-0233","abstract":"? 2017 IOP Publishing Ltd. Wireless capsule endoscopy is a non-invasive screening procedure of the gastrointestinal (GI) tract performed with an ingestible capsule endoscope (CE) of the size of a large vitamin pill. Such endoscopes are equipped with a usually low-frame-rate color camera which enables the visualization of the GI lumen and the detection of pathologies. The localization of the commercially available CEs is performed in the 3D abdominal space using radio-frequency (RF) triangulation from external sensor arrays, in combination with transit time estimation. State-of-the-art approaches, such as magnetic localization, which have been experimentally proved more accurate than the RF approach, are still at an early stage. Recently, we have demonstrated that CE localization is feasible using solely visual cues and geometric models. However, such approaches depend on camera parameters, many of which are unknown. In this paper the authors propose a novel non-parametric visual odometry (VO) approach to CE localization based on a feed-forward neural network architecture. The effectiveness of this approach in comparison to state-of-the-art geometric VO approaches is validated using a robotic-assisted in vitro experimental setup.","author":[{"dropping-particle":"","family":"Dimas","given":"George","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Iakovidis","given":"Dimitris K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Karargyris","given":"Alexandros","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ciuti","given":"Gastone","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Koulaouzidis","given":"Anastasios","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Measurement Science and Technology","id":"ITEM-2","issue":"9","issued":{"date-parts":[["2017","9","1"]]},"page":"094005","title":"An artificial neural network architecture for non-parametric visual odometry in wireless capsule endoscopy","type":"article-journal","volume":"28"},"uris":["",""]}],"mendeley":{"formattedCitation":"<sup>185,187</sup>","plainTextFormattedCitation":"185,187","previouslyFormattedCitation":"<sup>186,188</sup>"},"properties":{"noteIndex":0},"schema":""}185,187 A detailed discussion of CE locomotion is available elsewhereADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1055/s-0043-121882","ISSN":"2364-3722","PMID":"29399619","abstract":"<p>Background and study aims?Capsule endoscopy (CE) is invaluable for minimally invasive endoscopy of the gastrointestinal tract; however, several technological limitations remain including lack of reliable lesion localization. We present an approach to 3D reconstruction and localization using visual information from 2D CE images.</p>","author":[{"dropping-particle":"","family":"Koulaouzidis","given":"Anastasios","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Iakovidis","given":"Dimitris","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yung","given":"Diana","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mazomenos","given":"Evangelos","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bianchi","given":"Federico","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Karagyris","given":"Alexandros","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dimas","given":"George","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stoyanov","given":"Danail","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Thorlacius","given":"Henrik","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Toth","given":"Ervin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ciuti","given":"Gastone","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Endoscopy International Open","id":"ITEM-1","issue":"02","issued":{"date-parts":[["2018","2"]]},"page":"E205-E210","title":"Novel experimental and software methods for image reconstruction and localization in capsule endoscopy","type":"article-journal","volume":"06"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>185</sup>","plainTextFormattedCitation":"185","previouslyFormattedCitation":"<sup>186</sup>"},"properties":{"noteIndex":0},"schema":""}185. Current external localization methods such as radio frequency triangulation are integrated in the PillCam systems. Radio frequency localization algorithms are based on triangulation of the telemetry signals emitted by the CE device by external antennae (usually eight) located around the abdomen. This method was experimentally determined to have an average and maximum positional error of 37.7 mm and 114 mm respectivelyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.giec.2003.10.020","ISBN":"1052-5157 (Print)","ISSN":"10525157","PMID":"15062377","abstract":"The localization module helps the physicians in their attempt to improve the performance of capsule endoscopy and give precise information as to where the pathologies found in the examination are found. This will allow better planing of additional procedures or in case of needed surgery.","author":[{"dropping-particle":"","family":"Fischer","given":"Doron","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schreiber","given":"Reuven","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Levi","given":"Daphna","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Eliakim","given":"Rami","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastrointestinal Endoscopy Clinics of North America","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2004","1"]]},"page":"25-31","title":"Capsule endoscopy: the localization system","type":"article-journal","volume":"14"},"uris":["",""]}],"mendeley":{"formattedCitation":"<sup>188</sup>","plainTextFormattedCitation":"188","previouslyFormattedCitation":"<sup>189</sup>"},"properties":{"noteIndex":0},"schema":""}188,ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/RBME.2011.2171182","ISBN":"1937-3333 VO - 4","ISSN":"1937-3333","PMID":"22273791","abstract":"Wireless capsule endoscopy (WCE) can be considered an example of disruptive technology since it represents an appealing alternative to traditional diagnostic techniques. This technology enables inspection of the digestive system without discomfort or need for sedation, thus preventing the risks of conventional endoscopy, and has the potential of encouraging patients to undergo gastrointestinal (GI) tract examinations. However, currently available clinical products are passive devices whose locomotion is driven by natural peristalsis, with the drawback of failing to capture the images of important GI tract regions, since the doctor is unable to control the capsule's motion and orientation. To address these limitations, many research groups are working to develop active locomotion devices that allow capsule endoscopy to be performed in a totally controlled manner. This would enable the doctor to steer the capsule towards interesting pathological areas and to accomplish medical tasks. This review presents a research update on WCE and describes the state of the art of the basic modules of current swallowable devices, together with a perspective on WCE potential for screening, diagnostic, and therapeutic endoscopic procedures.","author":[{"dropping-particle":"","family":"Ciuti","given":"Gastone","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Menciassi","given":"Arianna","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dario","given":"Paolo","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Reviews in Biomedical Engineering","id":"ITEM-1","issued":{"date-parts":[["2011","1"]]},"page":"59-72","title":"Capsule Endoscopy: From Current Achievements to Open Challenges","type":"article-journal","volume":"4"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>189</sup>","plainTextFormattedCitation":"189","previouslyFormattedCitation":"<sup>190</sup>"},"properties":{"noteIndex":0},"schema":""}189. Accuracy is low but can be considered adequate for current wireless passive CE devices as they not require additional modules to be integrated and they do not require accurate pose information due to the lack of active motion control.Several academic teams have focused their research on other external localization techniques based on magnetic field sources that look to be a promising solution for active locomotion of CE devices, as a compromise between integration of components in a small space, computational complexity and overall accuracy. The main advantage of these approaches over other localization methodologies is that low-frequency magnetic signals can pass through human tissue without attenuation, which can be an advantage over radio frequency approaches depending on the frequencyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/JSEN.2009.2035711","ISSN":"1530-437X","author":[{"dropping-particle":"","family":"Hu","given":"Chao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Li","given":"Mao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Song","given":"Shuang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yang","given":"Wan'an","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zhang","given":"Rui","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Meng","given":"Max Q. -H.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Sensors Journal","id":"ITEM-1","issue":"5","issued":{"date-parts":[["2010","5"]]},"page":"903-913","title":"A Cubic 3-Axis Magnetic Sensor Array for Wirelessly Tracking Magnet Position and Orientation","type":"article-journal","volume":"10"},"uris":["",""]}],"mendeley":{"formattedCitation":"<sup>190</sup>","plainTextFormattedCitation":"190","previouslyFormattedCitation":"<sup>191</sup>"},"properties":{"noteIndex":0},"schema":""}190; additionally, magnetic sensors do not need line-of-sight vision to detect the capsule. Finally, the position and orientation accuracy of a magnetic-based localization approach is usually superior to that of radio frequency localization methods. For example a study by Taddese et al.ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"author":[{"dropping-particle":"","family":"Taddese","given":"Addisu Z.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Slawinski","given":"Piotr R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pirotta","given":"Marco","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Momi","given":"Elena","non-dropping-particle":"De","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Valdastri","given":"Pietro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Obstein","given":"Keith L.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"The International Journal of Robotics Research","id":"ITEM-1","issue":"under review","issued":{"date-parts":[["2018"]]},"title":"Enhanced Real-Time Pose Estimation for Closed Loop Robotic Manipulation of Magnetically Actuated Capsule Endoscopes","type":"article-journal"},"uris":["",""]}],"mendeley":{"formattedCitation":"<sup>191</sup>","plainTextFormattedCitation":"191","previouslyFormattedCitation":"<sup>192</sup>"},"properties":{"noteIndex":0},"schema":""}191 using magnetic-based localization was able to achieve a position and orientation accuracies lower than 5mm and 6° respectively. Magnetic localization methods are expected to take the lead over radio frequency approaches when they mature, and new design solutions for capsules with the required integrated sensors are achieved.[H2]Computer aided diagnosis Currently, CE devices can produce up to six6 frames per second (PillCam SB3, Given Imaging), generating thousands of images during passage through the gastrointestinal tract. Screening of the images can take 0.5 – 1?hr for a single human reader using high-speed reading techniquesADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1111/j.1572-0241.2003.08726.x","ISSN":"0002-9270","PMID":"14687814","abstract":"OBJECTIVE\\nThe average physician time required to view a wireless capsule endoscopy study at our institution is 50 min. It is unknown whether a nurse could preview the capsule endoscopy video and accurately detect all significant lesions. If so, it may allow the physician to review only the predetected abnormalities and thereby greatly reduce physician reading time. Our aim was to evaluate whether a nurse can accurately detect lesions on capsule endoscopy. \\n\\nMETHODS\\nAn endoscopy nurse who was trained to read capsule endoscopy reviewed 20 consecutive capsule endoscopy studies and recorded all findings. The same studies were viewed independently by a gastroenterologist. The two sets of recorded findings were reviewed, and a comparison of the accuracy in detecting landmarks and clinically significant lesions was made. \\n\\nRESULTS\\nThe nurse missed two of 27 significant lesions seen by the gastroenterologist (93% sensitivity, 95% CI = 74–99%), and the gastroenterologist missed three seen by the nurse. The nurse accurately recorded gastric emptying time and time of passage through the ileocecal valve to within 1 min of the times recorded by the gastroenterologist in 18 of 20 patients (90% agreement, 95% CI = 67–98%). \\n\\nCONCLUSIONS\\nIn this study, the endoscopy nurse detected 93% of the clinically significant lesions seen by the gastroenterologist. The clinical implication of this is that a physician extender could preread capsule endoscopies, allowing the gastroenterologist to view only the demarcated abnormalities. This could improve the cost effectiveness of capsule endoscopy and lead to wider physician acceptance of the test.","author":[{"dropping-particle":"","family":"Levinthal","given":"Gavin N.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Burke","given":"Carol A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Santisi","given":"Janice M.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"The American Journal of Gastroenterology","id":"ITEM-1","issue":"12","issued":{"date-parts":[["2003","12"]]},"page":"2669-2671","title":"The accuracy of an endoscopy nurse in interpreting capsule endoscopy","type":"article-journal","volume":"98"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>192</sup>","plainTextFormattedCitation":"192","previouslyFormattedCitation":"<sup>193</sup>"},"properties":{"noteIndex":0},"schema":""}192, which can lead to between 6%- to 20% of occurrences of pathology being missedADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1097/00042737-200603000-00009","ISBN":"0954-691X (Print)","ISSN":"0954691X","PMID":"16462542","abstract":"OBJECTIVE: Capsule endoscopy is a novel investigation for diagnosing small bowel diseases. However, its interpretation is highly subjective and the potential variability may compromise its accuracy and reliability. Here we studied the potential inter-observer variations on the interpretation of capsule endoscopy.\\n\\nMETHOD: Two residents and one specialist in gastroenterology independently reviewed 58 capsule endoscopy studies in the same sequential order. The gastric transit time, small bowel transit time, and the most significant small bowel lesion were independently recorded. The consensus transit time was determined by the joint review of the three gastroenterologists. The 'gold standard' for small bowel diagnoses was based on final surgical, endoscopic findings or consensus diagnosis.\\n\\nRESULTS: Clinically significant and relevant small bowel lesions were found in 32 (55%) cases by consensus review. The overall mean accuracy in determining gastric emptying time, small bowel transit time and small bowel lesion was 89%, 76% and 80%, respectively. There was a significant difference in the accuracy between the residents and specialist on small bowel transit time (P<0.05) and small bowel diagnosis (P<0.05). The mean kappa values on small bowel diagnosis among the three viewers was 0.56 (range, 0.52-0.59). Among various small bowel diagnoses, small bowel bleeding was more accurately identified than other pathology.\\n\\nCONCLUSIONS: Our results show that there is moderate degree of inter-observer discrepancies on the interpretation of capsule endoscopy. A second reading by an experienced viewer might improve the diagnostic accuracy of this investigation.","author":[{"dropping-particle":"","family":"Lai","given":"Larry H.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wong","given":"Grace L.H.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chow","given":"Dorothy K.L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lau","given":"James Y.W.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sung","given":"Joseph J.Y.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leung","given":"Wai K.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"European Journal of Gastroenterology and Hepatology","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2006"]]},"page":"283-286","title":"Inter-observer variations on interpretation of capsule endoscopies","type":"article-journal","volume":"18"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1055/s-2008-1027822","ISSN":"0044-2771","PMID":"19280540","abstract":"BACKGROUND: Capsule endoscopy is a common, pain-free diagnostic procedure for the small bowel. However, interpretation of the whole video recording is a time-consuming and costly procedure that can take up to 2 hours. The aim of the present study is two-fold: first to study the accuracy of capsule endoscopy analysis between a trained endoscopy nurse and a physician and secondly to determine if pre-evaluation by nursing staff might be time-effective for capsule reading. This study is especially important given the increasing financial pressure on current health-care systems. METHODS: A long-standing experienced endoscopy nurse, who was trained to read capsule endoscopy, and a physician, both blinded to the patient diagnosis and the other clinical findings reviewed 48 consecutive capsule endoscopy videos. The analyses of both the nurse and the physician were re-evaluated by an independent doctor regarding the agreement of the marked findings. RESULTS: Total time to read capsule endoscopy was significantly longer for the nurse's interpretation (63 +/- 26 min) as compared to the physician's interpretation (54 +/- 18 min, p < 0.01). The endoscopy nurse marked 236 thumbnails, whereas the doctor only marked 132 thumbnails. The nurse overlooked 4 of 64 relevant lesions (6 %), which had been detected by the physician. These overlooked lesions were not single important lesions, they were overlooked only in patients with multiple angiectasias of the small intestine, and thus the misdiagnosis was without clinical relevance. The physician overlooked 6 of 68 lesions detected by the nurse (9 %), also in patients with multiple angiodysplastic lesions and therefore without clinical relevance. On post-hoc analysis of the capsule video recordings the time needed by the physician to interpret the thumbnails marked by the nurse was 10 +/- 12 min. While there was no difference with respect to the estimated gastric emptying time (nurse 27 +/- 13 min vs. physician 28 +/- 14 min, n. s.), the estimated time of capsule passage through the ileocaecal valve was longer when interpreted by the endoscopy nurse (nurse 347 +/- 89 min vs. physician 326 +/- 74 min, n. s.). Nevertheless, the total cost for capsule pre-evaluation by the nurse was lower (13.23 euro vs. physician 17.82 euro). CONCLUSION: The endoscopy nurse detected 94 % of the significant lesions seen by the physician and no clinically relevant findings were overlooked. A pre-evaluation of the capsule video by trained staff …","author":[{"dropping-particle":"","family":"Riphaus","given":"A","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Richter","given":"S","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Vonderach","given":"M","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wehrmann","given":"T","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Z Gastroenterol","id":"ITEM-2","issue":"3","issued":{"date-parts":[["2009"]]},"page":"273-6","title":"Capsule endoscopy interpretation by an endoscopy nurse - a comparative trial.","type":"article-journal","volume":"47"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1097/MEG.0b013e3283433abf","ISSN":"0954691X","PMID":"21287720","abstract":"Objective: Complete review of wireless capsule endoscopy (WCE) recordings by a physician is time-consuming and laborious and may be perceived as a limitation to perform WCE. The aim of this study was to evaluate the efficacy of a nurse in interpreting WCE. Methods: A total of 102 WCE videos were evaluated by a single gastroenterologist and a nurse experienced as an assistant in diagnostic and interventional endoscopy and trained in WCE. After independently reviewing WCE videos, the two readers discussed their findings and came to a consensus. Results: The mean capsule reading time was significantly longer for the nurse compared with the gastroenterologist (117.3±24.8 vs. 63.8±8.5 min, P<0.001). No statistical differences were observed regarding the correct recognition of first gastric, duodenal and caecal images between the two readers. For the gastroenterologist, both sensitivity and specificity in detecting abnormal findings were 100% except for angiodysplasia [sensitivity 88.5%, 95% confidence interval (CI): 70-97.4]. For the nurse, the lowest sensitivity rates were in detecting polyps (70%, 95% CI: 34.9-92.3) and angiodysplasias (92.3%, 95% CI: 74.8-98.9). The interobserver agreement as determined by Cohen's κ coefficient was excellent except for polyps (k=0.71, 95% CI: 0.46-0.96). Conclusion: A trained nurse is highly accurate in detecting abnormal findings and interpreting WCE recordings. Physician's role could be limited to consider and confirm thumbnails created by a nurse. ? 2011 Wolters Kluwer Health | Lippincott Williams &Wilkins.","author":[{"dropping-particle":"","family":"Dokoutsidou","given":"Helen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Karagiannis","given":"Stefanos","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Giannakoulopoulou","given":"Eleftheria","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Galanis","given":"Petros","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kyriakos","given":"Nikolaos","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Liatsos","given":"Christos","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Faiss","given":"Siegbert","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mavrogiannis","given":"Christos","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"European Journal of Gastroenterology and Hepatology","id":"ITEM-3","issue":"2","issued":{"date-parts":[["2011"]]},"page":"166-170","title":"A study comparing an endoscopy nurse and an endoscopy physician in capsule endoscopy interpretation","type":"article-journal","volume":"23"},"uris":[""]},{"id":"ITEM-4","itemData":{"DOI":"10.1111/j.1572-0241.2003.08726.x","ISSN":"0002-9270","PMID":"14687814","abstract":"OBJECTIVE\\nThe average physician time required to view a wireless capsule endoscopy study at our institution is 50 min. It is unknown whether a nurse could preview the capsule endoscopy video and accurately detect all significant lesions. If so, it may allow the physician to review only the predetected abnormalities and thereby greatly reduce physician reading time. Our aim was to evaluate whether a nurse can accurately detect lesions on capsule endoscopy. \\n\\nMETHODS\\nAn endoscopy nurse who was trained to read capsule endoscopy reviewed 20 consecutive capsule endoscopy studies and recorded all findings. The same studies were viewed independently by a gastroenterologist. The two sets of recorded findings were reviewed, and a comparison of the accuracy in detecting landmarks and clinically significant lesions was made. \\n\\nRESULTS\\nThe nurse missed two of 27 significant lesions seen by the gastroenterologist (93% sensitivity, 95% CI = 74–99%), and the gastroenterologist missed three seen by the nurse. The nurse accurately recorded gastric emptying time and time of passage through the ileocecal valve to within 1 min of the times recorded by the gastroenterologist in 18 of 20 patients (90% agreement, 95% CI = 67–98%). \\n\\nCONCLUSIONS\\nIn this study, the endoscopy nurse detected 93% of the clinically significant lesions seen by the gastroenterologist. The clinical implication of this is that a physician extender could preread capsule endoscopies, allowing the gastroenterologist to view only the demarcated abnormalities. This could improve the cost effectiveness of capsule endoscopy and lead to wider physician acceptance of the test.","author":[{"dropping-particle":"","family":"Levinthal","given":"Gavin N.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Burke","given":"Carol A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Santisi","given":"Janice M.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"The American Journal of Gastroenterology","id":"ITEM-4","issue":"12","issued":{"date-parts":[["2003","12"]]},"page":"2669-2671","title":"The accuracy of an endoscopy nurse in interpreting capsule endoscopy","type":"article-journal","volume":"98"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>192–195</sup>","plainTextFormattedCitation":"192–195","previouslyFormattedCitation":"<sup>193–196</sup>"},"properties":{"noteIndex":0},"schema":""}192–195. This issue will be exacerbated both by an increase in the number of modalities provided by a capsule and by increased CE usage owing to reduced costs. Initial approaches to automate aspects of capsule data interpretation using color image analysis to create a suspected blood indicator have been developed. However, reception by the clinical community has been mixedADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.bspc.2017.10.011","ISSN":"17468108","abstract":"Capsule Endoscopy (CE) is a non-invasive clinical procedure that allows examination of the entire gastrointestinal tract including parts of small intestine beyond the scope of conventional endoscope. It requires computer-aided approach for the assessment of video frames to reduce diagnosis time. This paper presents a computer-assisted method based on a classifier fusion algorithm which combines two optimized Support Vector Machine (SVM) classifiers to automatically detect bleeding regions present in CE frames. The classifiers are based on RGB and HSV color spaces; the image regions are characterized on the basis of statistical features derived from the first-order histogram probability of respective color channels. A nested cross validation strategy has been adopted for the parameter tuning and feature selection to optimize the classifiers. The optimum feature sets for the best performance are evaluated after exhaustive analysis. The proposed fusion approach achieves an average accuracy of 95%, sensitivity of 94% and specificity of 95.3% for a dataset of 8872 CE frames, which is higher than that obtained from a single classifier. Comparison with the state-of-the-art algorithms exhibits that the proposed method yields superior performance for diverse dataset.","author":[{"dropping-particle":"","family":"Deeba","given":"Farah","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Islam","given":"Monzurul","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bui","given":"Francis M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wahid","given":"Khan A.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Biomedical Signal Processing and Control","id":"ITEM-1","issued":{"date-parts":[["2018"]]},"page":"415-424","publisher":"Elsevier Ltd","title":"Performance assessment of a bleeding detection algorithm for endoscopic video based on classifier fusion method and exhaustive feature selection","type":"article-journal","volume":"40"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1016/j.cmpb.2015.09.005","ISSN":"18727565","PMID":"26390947","abstract":"Background and objective: Wireless Capsule Endoscopy (WCE) can image the portions of the human gastrointestinal tract that were previously unreachable for conventional endoscopy examinations. A major drawback of this technology is that a large volume of data are to be analyzed in order to detect a disease which can be time-consuming and burdensome for the clinicians. Consequently, there is a dire need of computer-aided disease detection schemes to assist the clinicians. In this paper, we propose a real-time, computationally efficient and effective computerized bleeding detection technique applicable for WCE technology. Methods: The development of our proposed technique is based on the observation that characteristic patterns appear in the frequency spectrum of the WCE frames due to the presence of bleeding region. Discovering these discriminating patterns, we develop a texture-feature-descriptor-based-algorithm that operates on the Normalized Gray Level Co-occurrence Matrix (NGLCM) of the magnitude spectrum of the images. A new local texture descriptor called difference average that operates on NGLCM is also proposed. We also perform statistical validation of the proposed scheme. Results: The proposed algorithm was evaluated using a publicly available WCE database. The training set consisted of 600 bleeding and 600 non-bleeding frames. This set was used to train the SVM classifier. On the other hand, 860 bleeding and 860 non-bleeding images were selected from the rest of the extracted images to form the test set. The accuracy, sensitivity and specificity obtained from our method are 99.19%, 99.41% and 98.95% respectively which are significantly higher than state-of-the-art methods. In addition, the low computational cost of our method makes it suitable for real-time implementation. Conclusion: This work proposes a bleeding detection algorithm that employs textural features from the magnitude spectrum of the WCE images. Experimental outcomes backed by statistical validations prove that the proposed algorithm is superior to the existing ones in terms of accuracy, sensitivity, specificity and computational cost.","author":[{"dropping-particle":"","family":"Hassan","given":"Ahnaf Rashik","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Haque","given":"Mohammad Ariful","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Computer Methods and Programs in Biomedicine","id":"ITEM-2","issue":"3","issued":{"date-parts":[["2015"]]},"page":"341-353","publisher":"Elsevier Ireland Ltd","title":"Computer-aided gastrointestinal hemorrhage detection in wireless capsule endoscopy videos","type":"article-journal","volume":"122"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1007/s10916-014-0025-1","ISBN":"1091601400251","ISSN":"1573689X","PMID":"24696394","abstract":"Wireless Capsule Endoscopy (WCE) is a technology in the field of endoscopic imaging which facilitates direct visualization of the entire small intestine. Many algorithms are being developed to automatically identify clinically important frames in WCE videos. This paper presents a supervised method for automated detection of bleeding regions present in WCE frames or images. The proposed method characterizes the image regions by using statistical features derived from the first order histogram probability of the three planes of RGB color space. Despite being inconsistent and tiresome, manual selection of regions has been a popular technique for creating training data in the studies of capsule endoscopic images. We propose a semi-automatic region-annotation algorithm for creating training data efficiently. All possible combinations of different features are exhaustively analyzed to find the optimum feature set with the best performance. During operation, regions from images are obtained by applying a segmentation method. Finally, a trained neural network recognizes the patterns of the data arising from bleeding and non-bleeding regions.","author":[{"dropping-particle":"","family":"Sainju","given":"Sonu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bui","given":"Francis M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wahid","given":"Khan A.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Medical Systems","id":"ITEM-3","issue":"4","issued":{"date-parts":[["2014"]]},"title":"Automated bleeding detection in capsule endoscopy videos using statistical features and region growing","type":"article-journal","volume":"38"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>196–198</sup>","plainTextFormattedCitation":"196–198","previouslyFormattedCitation":"<sup>197–199</sup>"},"properties":{"noteIndex":0},"schema":""}196–198 owing to its limited sensitivity and specificity, which one studyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.cgh.2007.12.029","ISSN":"15423565","author":[{"dropping-particle":"","family":"Buscaglia","given":"Jonathan M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Giday","given":"Samuel A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"V.","family":"Kantsevoy","given":"Sergey","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Clarke","given":"John O.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Magno","given":"Priscilla","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yong","given":"Elaine","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mullin","given":"Gerard E.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Clinical Gastroenterology and Hepatology","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2008","3"]]},"page":"298-301","title":"Performance Characteristics of the Suspected Blood Indicator Feature in Capsule Endoscopy According to Indication for Study","type":"article-journal","volume":"6"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>199</sup>","plainTextFormattedCitation":"199","previouslyFormattedCitation":"<sup>200</sup>"},"properties":{"noteIndex":0},"schema":""}199 has characterized as 56.4% and 33.5% respectively. Computer aided diagnosis (CADx)CADx can be defined as the use of computer algorithms to process and interpret medical data for the purposes of identifying pathology. This approach is relatively new in gastroenterology but similar techniques are widely used in radiology, with several systems already approved by the FDAADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/pmedimag.2007.02.002","ISBN":"0895-6111 (Print)\\r0895-6111 (Linking)","ISSN":"08956111","PMID":"17349778","abstract":"Computer-aided diagnosis (CAD) has become one of the major research subjects in medical imaging and diagnostic radiology. In this article, the motivation and philosophy for early development of CAD schemes are presented together with the current status and future potential of CAD in a PACS environment. With CAD, radiologists use the computer output as a “second opinion” and make the final decisions. CAD is a concept established by taking into account equally the roles of physicians and computers, whereas automated computer diagnosis is a concept based on computer algorithms only. With CAD, the performance by computers does not have to be comparable to or better than that by physicians, but needs to be complementary to that by physicians. In fact, a large number of CAD systems have been employed for assisting physicians in the early detection of breast cancers on mammograms. A CAD scheme that makes use of lateral chest images has the potential to improve the overall performance in the detection of lung nodules when combined with another CAD scheme for PA chest images. Because vertebral fractures can be detected reliably by computer on lateral chest radiographs, radiologists’ accuracy in the detection of vertebral fractures would be improved by the use of CAD, and thus early diagnosis of osteoporosis would become possible. In MRA, a CAD system has been developed for assisting radiologists in the detection of intracranial aneurysms. On successive bone scan images, a CAD scheme for detection of interval changes has been developed by use of temporal subtraction images. In the future, many CAD schemes could be assembled as packages and implemented as a part of PACS. For example, the package for chest CAD may include the computerized detection of lung nodules, interstitial opacities, cardiomegaly, vertebral fractures, and interval changes in chest radiographs as well as the computerized classification of benign and malignant nodules and the differential diagnosis of interstitial lung diseases. In order to assist in the differential diagnosis, it would be possible to search for and retrieve images (or lesions) with known pathology, which would be very similar to a new unknown case, from PACS when a reliable and useful method has been developed for quantifying the similarity of a pair of images for visual comparison by radiologists.","author":[{"dropping-particle":"","family":"Doi","given":"Kunio","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Comput Med Imaging Graph","id":"ITEM-1","issue":"4-5","issued":{"date-parts":[["2007"]]},"page":"198-211","title":"Computer-aided diagnosis in medical imaging: Historical review, current status and future potential","type":"article-journal","volume":"31"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>200</sup>","plainTextFormattedCitation":"200","previouslyFormattedCitation":"<sup>201</sup>"},"properties":{"noteIndex":0},"schema":""}200. Algorithms to automate the detection of lesionsADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.media.2016.04.007","ISSN":"13618423","PMID":"27236223","abstract":"The gastrointestinal endoscopy in this study refers to conventional gastroscopy and wireless capsule endoscopy (WCE). Both of these techniques produce a large number of images in each diagnosis. The lesion detection done by hand from the images above is time consuming and inaccurate. This study designed a new computer-aided method to detect lesion images. We initially designed an algorithm named joint diagonalisation principal component analysis (JDPCA), in which there are no approximation, iteration or inverting procedures. Thus, JDPCA has a low computational complexity and is suitable for dimension reduction of the gastrointestinal endoscopic images. Then, a novel image feature extraction method was established through combining the algorithm of machine learning based on JDPCA and conventional feature extraction algorithm without learning. Finally, a new computer-aided method is proposed to identify the gastrointestinal endoscopic images containing lesions. The clinical data of gastroscopic images and WCE images containing the lesions of early upper digestive tract cancer and small intestinal bleeding, which consist of 1330 images from 291 patients totally, were used to confirm the validation of the proposed method. The experimental results shows that, for the detection of early oesophageal cancer images, early gastric cancer images and small intestinal bleeding images, the mean values of accuracy of the proposed method were 90.75%, 90.75% and 94.34%, with the standard deviations (SDs) of 0.0426, 0.0334 and 0.0235, respectively. The areas under the curves (AUCs) were 0.9471, 0.9532 and 0.9776, with the SDs of 0.0296, 0.0285 and 0.0172, respectively. Compared with the traditional related methods, our method showed a better performance. It may therefore provide worthwhile guidance for improving the efficiency and accuracy of gastrointestinal disease diagnosis and is a good prospect for clinical application.","author":[{"dropping-particle":"","family":"Liu","given":"Ding Yun","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gan","given":"Tao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rao","given":"Ni Ni","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Xing","given":"Yao Wen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zheng","given":"Jie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Li","given":"Sang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Luo","given":"Cheng Si","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zhou","given":"Zhong Jun","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wan","given":"Yong Li","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Medical Image Analysis","id":"ITEM-1","issued":{"date-parts":[["2016"]]},"page":"281-294","publisher":"Elsevier B.V.","title":"Identification of lesion images from gastrointestinal endoscope based on feature extraction of combinational methods with and without learning process","type":"article-journal","volume":"32"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1109/ICIP.2014.7025453","ISBN":"9781479957514","author":[{"dropping-particle":"","family":"Iakovidis","given":"Dimitris K","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Koulaouzidis","given":"Anastasios","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Image Processing (ICIP), 2014 IEEE International Conference on. IEEE","id":"ITEM-2","issued":{"date-parts":[["2014"]]},"page":"2236-2240","title":"Automatic lesion detection in wireless capsule endoscopy - A simple solution for a complex problem","type":"article-journal"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.3748/wjg.14.6929","ISBN":"8628854223","ISSN":"10079327","PMID":"19058327","abstract":"AIM: To investigate and evaluate the feasibility of the computer-aided screening diagnosis for enteric lesions in the capsule endoscopy (CE). METHODS: After developing a series of algorithms for the screening diagnosis of the enteric lesions in CE based on their characteristic colors and contours, the normal and abnormal images obtained from 289 patients were respectively scanned and diagnosed by the CE readers and by the computer-aided screening for the enteric lesions with the image-processed software (IPS). The enteric lesions shown by the images included esoenteritis, mucosal ulcer and erosion, bleeding, space-occupying lesions, angioectasia, diverticula, parasites, etc. The images for the lesions or the suspected lesions confirmed by the CE readers and the computers were collected, and the effectiveness rate of the screening and the number of the scanned images were evaluated, respectively. RESULTS: Compared with the diagnostic results obtained by the CE readers, the total effectiveness rate (sensitivity) in the screening of the commonly-encountered enteric lesions by IPS varied from 42.9% to 91.2%, with a median of 74.2%, though the specificity and the accuracy rates were still low, and the images for the rarely-encountered lesions were difficult to differentiate from the normal images. However, the number of the images screened by IPS was 5000 on average, and only 10%-15% of the original images were left behind. As a result, a large number of normal images were excluded, and the reading time decreased from 5 h to 1 h on average. CONCLUSION: Though the total accuracy and specificity rates by the computer-aided screening for the enteric lesions with IPS are much lower than those by the CE readers, the computer-aided screening diagnosis can exclude a large number of the normal images and confine the enteric lesions to 5000 images on average, which can reduce the workload of the readers in the scanning of the images. This computer-aided screening technique can make a correct diagnosis as efficiently as possible in most of the patients.","author":[{"dropping-particle":"","family":"Gan","given":"Tao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wu","given":"Jun Chao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rao","given":"Ni Ni","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chen","given":"Tao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Liu","given":"Bing","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"World Journal of Gastroenterology","id":"ITEM-3","issue":"45","issued":{"date-parts":[["2008"]]},"page":"6929-6935","title":"A feasibility trial of computer-aided diagnosis for enteric lesions in capsule endoscopy","type":"article-journal","volume":"14"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>201–203</sup>","plainTextFormattedCitation":"201–203","previouslyFormattedCitation":"<sup>202–204</sup>"},"properties":{"noteIndex":0},"schema":""}201–203, ulcersADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/ROBIO.2009.5420455","ISBN":"9781424447756","author":[{"dropping-particle":"","family":"Li","given":"Baopu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Qi","given":"Lin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Meng","given":"Max Q","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ieee","given":"Fellow","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fan","given":"Yichen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Member","given":"Student","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE International Conference on Robotics and Biomimetics","id":"ITEM-1","issued":{"date-parts":[["2009"]]},"page":"2326-2331","title":"Using ensemble classifier for small bowel ulcer detection in wireless capsule endoscopy images","type":"article-journal"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1109/CBMS.2013.6627801","ISBN":"9781479910533","ISSN":"10637125","author":[{"dropping-particle":"","family":"Eid","given":"Alexis","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Charisis","given":"Vasileios S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hadjileontiadis","given":"Leontios J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sergiadis","given":"George D.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Proceedings of CBMS 2013 - 26th IEEE International Symposium on Computer-Based Medical Systems","id":"ITEM-2","issued":{"date-parts":[["2013"]]},"page":"273-278","title":"A curvelet-based lacunarity approach for ulcer detection from Wireless Capsule Endoscopy images","type":"article-journal"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1109/ECS.2015.7124881","ISBN":"9781479972241","abstract":"? 2015 IEEE. The entire visualization of GastroIntestinal (GI) tract is not possible with conventional endoscopic exams. Wireless Capsule Endoscopy (WCE) is a low risk, painless, noninvasive procedure for diagnosing diseases such as bleeding, polyps, ulcers, and Crohns disease within the human digestive tract, especially the small intestine that was unreachable using the traditional endoscopic methods. However, analysis of massive images of WCE detection is tedious and time consuming to physicians. Hence, researchers have developed software methods to detect these diseases automatically. Thus, the effectiveness of WCE can be improved. In this paper, a novel textural feature extraction method is proposed based on Contourlet transform and Log Gabor filter to distinguish ulcer regions from normal regions. The results show that the proposed method performs well with a high accuracy rate of 94.16% using Support Vector Machine (SVM) classifier in HSV colour space.","author":[{"dropping-particle":"","family":"Koshy","given":"Nimisha Elsa","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gopi","given":"Varun P.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"2nd International Conference on Electronics and Communication Systems, ICECS 2015","id":"ITEM-3","issued":{"date-parts":[["2015"]]},"page":"1725-1729","title":"A new method for ulcer detection in endoscopic images","type":"paper-conference"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>204–206</sup>","plainTextFormattedCitation":"204–206","previouslyFormattedCitation":"<sup>205–207</sup>"},"properties":{"noteIndex":0},"schema":""}204–206, tumoursADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/TITB.2012.2185807","ISBN":"1089-7771","ISSN":"10897771","PMID":"22287246","abstract":"Tumor in digestive tract is a common disease and wireless capsule endoscopy (WCE) is a relatively new technology to examine diseases for digestive tract especially for small intestine. This paper addresses the problem of automatic recognition of tumor for WCE images. Candidate color texture feature that integrates uniform local binary pattern and wavelet is proposed to characterize WCE images. The proposed features are invariant to illumination change and describe multiresolution characteristics of WCE images. Two feature selection approaches based on support vector machine, sequential forward floating selection and recursive feature elimination, are further employed to refine the proposed features for improving the detection accuracy. Extensive experiments validate that the proposed computer-aided diagnosis system achieves a promising tumor recognition accuracy of 92.4% in WCE images on our collected data.","author":[{"dropping-particle":"","family":"Li","given":"Baopu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Meng","given":"Max Q H","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Transactions on Information Technology in Biomedicine","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2012"]]},"page":"323-329","title":"Tumor recognition in wireless capsule endoscopy images using textural features and SVM-based feature selection","type":"article-journal","volume":"16"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1016/pbiomed.2016.01.021","ISBN":"0010-4825","ISSN":"18790534","PMID":"26829705","abstract":"Wireless capsule endoscopy (WCE) has been a revolutionary technique to noninvasively inspect gastrointestinal (GI) tract diseases, especially small bowel tumor. However, it is a tedious task for physicians to examine captured images. To develop a computer-aid diagnosis tool for relieving the huge burden of physicians, the intestinal video data from 89 clinical patients with the indications of potential tumors was analyzed. Out of the 89 patients, 15(16.8%) were diagnosed with small bowel tumor. A novel set of textural features that integrate multi-scale curvelet and fractal technology were proposed to distinguish normal images from tumor images. The second order textural descriptors as well as higher order moments between different color channels were computed from images synthesized by the inverse curvelet transform of the selected scales. Then, a classification approach based on support vector machine (SVM) and genetic algorithm (GA) was further employed to select the optimal feature set and classify the real small bowel images. Extensive comparison experiments validate that the proposed automatic diagnosis scheme achieves a promising tumor classification performance of 97.8% sensitivity and 96.7% specificity in the selected images from our clinical data.","author":[{"dropping-particle":"","family":"Liu","given":"Gang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yan","given":"Guozheng","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kuang","given":"Shuai","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wang","given":"Yongbing","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Computers in Biology and Medicine","id":"ITEM-2","issued":{"date-parts":[["2016"]]},"page":"131-138","publisher":"Elsevier","title":"Detection of small bowel tumor based on multi-scale curvelet analysis and fractal technology in capsule endoscopy","type":"article-journal","volume":"70"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1186/1475-925X-11-3","ISSN":"1475925X","PMID":"22236465","abstract":"BACKGROUND: Wireless capsule endoscopy has been introduced as an innovative, non-invasive diagnostic technique for evaluation of the gastrointestinal tract, reaching places where conventional endoscopy is unable to. However, the output of this technique is an 8 hours video, whose analysis by the expert physician is very time consuming. Thus, a computer assisted diagnosis tool to help the physicians to evaluate CE exams faster and more accurately is an important technical challenge and an excellent economical opportunity. METHOD: The set of features proposed in this paper to code textural information is based on statistical modeling of second order textural measures extracted from co-occurrence matrices. To cope with both joint and marginal non-Gaussianity of second order textural measures, higher order moments are used. These statistical moments are taken from the two-dimensional color-scale feature space, where two different scales are considered. Second and higher order moments of textural measures are computed from the co-occurrence matrices computed from images synthesized by the inverse wavelet transform of the wavelet transform containing only the selected scales for the three color channels. The dimensionality of the data is reduced by using Principal Component Analysis. RESULTS: The proposed textural features are then used as the input of a classifier based on artificial neural networks. Classification performances of 93.1% specificity and 93.9% sensitivity are achieved on real data. These promising results open the path towards a deeper study regarding the applicability of this algorithm in computer aided diagnosis systems to assist physicians in their clinical practice.","author":[{"dropping-particle":"","family":"Barbosa","given":"Daniel C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Roupar","given":"Dalila B.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ramos","given":"Jaime C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tavares","given":"Adriano C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lima","given":"Carlos S.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"BioMedical Engineering Online","id":"ITEM-3","issue":"1","issued":{"date-parts":[["2012"]]},"page":"3","publisher":"BioMed Central Ltd","title":"Automatic small bowel tumor diagnosis by using multi-scale wavelet-based analysis in wireless capsule endoscopy images","type":"article-journal","volume":"11"},"uris":[""]},{"id":"ITEM-4","itemData":{"DOI":"10.1109/IEMBS.2009.5334013","ISBN":"9781424432967","ISSN":"1557-170X","PMID":"19964706","abstract":"Traditional endoscopic methods do not allow the visualization of the entire Gastrointestinal (GI) tract. Wireless Capsule Endoscopy (CE) is a diagnostic procedure that overcomes this limitation of the traditional endoscopic methods. The CE video frames possess rich information about the condition of the stomach and intestine mucosa, encoded as color and texture patterns. It is known for a long time that human perception of texture is based in a multi-scale analysis of patterns, which can be modeled by multi-resolution approaches. Furthermore, modeling the covariance of textural descriptors has been successfully used in classification of colonoscopy videos. Therefore, in the present paper it is proposed a frame classification scheme based on statistical textural descriptors taken from the Discrete Curvelet Transform (DCT) domain, a recent multi-resolution mathematical tool. The DCT is based on an anisotropic notion of scale and high directional sensitivity in multiple directions, being therefore suited to characterization of complex patterns as texture. The covariance of texture descriptors taken at a given detail level, in different angles, is used as classification feature, in a scheme designated as Color Curvelet Covariance. The classification step is performed by a multilayer perceptron neural network. The proposed method has been applied in real data taken from several capsule endoscopic exams and reaches 97.2% of sensitivity and 97.4% specificity. These promising results support the feasibility of the proposed method.","author":[{"dropping-particle":"","family":"Barbosa","given":"Daniel J.C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ramos","given":"Jaime","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Correia","given":"José Higino","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lima","given":"Carlos S.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Proceedings of the 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society: Engineering the Future of Biomedicine, EMBC 2009","id":"ITEM-4","issued":{"date-parts":[["2009"]]},"page":"6683-6686","title":"Automatic detection of small bowel tumors in capsule endoscopy based on color curvelet covariance statistical texture descriptors","type":"article-journal"},"uris":[""]},{"id":"ITEM-5","itemData":{"DOI":"10.1016/j.artmed.2011.01.003","ISBN":"0933-3657","ISSN":"09333657","PMID":"21353503","abstract":"Objective: Capsule endoscopy is useful in the diagnosis of small bowel diseases. However, the large number of images produced in each test is a tedious task for physicians. To relieve burden of physicians, a new computer-aided detection scheme is developed in this study, which aims to detect small bowel tumors for capsule endoscopy. Methods and materials: A novel textural feature based on multi-scale local binary pattern is proposed to discriminate tumor images from normal images. Since tumor in small bowel exhibit great diversities in appearance, multiple classifiers are employed to improve detection accuracy. 1200 capsule endoscopy images chosen from 10 patients' data constitute test data in our experiment. Results: Multiple classifiers based on k-nearest neighbor, multilayer perceptron neural network and support vector machine, which are built from six different ensemble rules, are experimented in three different color spaces. The results demonstrate an encouraging detection accuracy of 90.50%, together with a sensitivity of 92.33% and a specificity of 88.67%. Conclusion: The proposed scheme using color texture features and classifier ensemble is promising for small bowel tumor detection in capsule endoscopy images. ? 2011 Elsevier B.V.","author":[{"dropping-particle":"","family":"Li","given":"Baopu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Meng","given":"Max Q.H.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lau","given":"James Y.W.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Artificial Intelligence in Medicine","id":"ITEM-5","issue":"1","issued":{"date-parts":[["2011"]]},"page":"11-16","publisher":"Elsevier B.V.","title":"Computer-aided small bowel tumor detection for capsule endoscopy","type":"article-journal","volume":"52"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>207–211</sup>","plainTextFormattedCitation":"207–211","previouslyFormattedCitation":"<sup>208–212</sup>"},"properties":{"noteIndex":0},"schema":""}207–211 and polypsADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"author":[{"dropping-particle":"V","family":"Mamonov","given":"Alexander","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Figueiredo","given":"Isabel N","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Figueiredo","given":"Pedro N","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tsai","given":"Yen-hsi Richard","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Ices Report 13-10","id":"ITEM-1","issue":"7","issued":{"date-parts":[["2013"]]},"page":"1-16","title":"Automated polyp detection in colon capsule endoscopy by Automated polyp detection in colon capsule endoscopy","type":"article-journal","volume":"33"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>212</sup>","plainTextFormattedCitation":"212","previouslyFormattedCitation":"<sup>213</sup>"},"properties":{"noteIndex":0},"schema":""}212 from images and video taken with commercial WLI CE devices in the gastrointestinal tract have been reported, with bleedingADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/JBHI.2013.2257819","ISBN":"2168-2194 VO - 18","ISSN":"21682194","PMID":"24608063","abstract":"Wireless capsule endoscopy (WCE) can directly take digital images in the gastrointestinal tract of a patient. It has opened a new chapter in small intestine examination. However, a major problem associated with this technology is that too many images need to be manually examined by clinicians. Currently, there is no standard for capsule endoscopy image interpretation and classification. Most state-of-the-art CAD methods often suffer from poor performance, high computational cost, or multiple empirical thresholds. In this paper, a new method for rapid bleeding detection in the WCE video is proposed. We group pixels through superpixel segmentation to reduce the computational complexity while maintaining high diagnostic accuracy. Feature of each superpixel is extracted using the red ratio in RGB space and fed into support vector machine for classification. Also, the influence of edge pixels has been removed in this paper. Comparative experiments show that our algorithm is superior to the existing methods in terms of sensitivity, specificity, and accuracy.","author":[{"dropping-particle":"","family":"Fu","given":"Yanan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zhang","given":"Wei","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mandal","given":"Mrinal","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Meng","given":"Max Q H","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Journal of Biomedical and Health Informatics","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2014"]]},"page":"636-642","title":"Computer-aided bleeding detection in WCE video","type":"article-journal","volume":"18"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.4236/jsea.2014.75039","ISSN":"1945-3116","abstract":"Wireless capsule endoscopes (WCEs) have been used widely to detect abnormalities inside regions of the small intestine that are not accessible when using traditional endoscopy techniques. However, an experienced clinician must spend an average of 2 hours to view and analyze the approximately 60,000 images produced during one examination. Therefore, developing a computer-aided system for processing WCE images is crucial. This paper proposes a novel method used for detecting bleeding and ulcers in WCE images. This approach involves using color features to determine the status of the small intestine. The experimental results revealed that the proposed scheme is promising in detecting bleeding and ulcer regions.","author":[{"dropping-particle":"","family":"Yeh","given":"Jinn-Yi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wu","given":"Tai-Hsi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tsai","given":"Wei-Jun","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Software Engineering and Applications","id":"ITEM-2","issue":"05","issued":{"date-parts":[["2014"]]},"page":"422-432","title":"Bleeding and Ulcer Detection Using Wireless Capsule Endoscopy Images","type":"article-journal","volume":"07"},"uris":[""]},{"id":"ITEM-3","itemData":{"ISBN":"9781457721779","author":[{"dropping-particle":"","family":"Xiaoying Liu, lia Gu, Yaoqin Xie","given":"lun Xiong and Wenjian Qin","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE-EMBS International Conference on Biomedical and Health Informatics","id":"ITEM-3","issue":"Bhi","issued":{"date-parts":[["2012"]]},"page":"737-740","title":"A New Approach to Detecting Ulcer and Bleeding in Wireless Capsule Endoscopy Images","type":"article-journal","volume":"25"},"uris":[""]},{"id":"ITEM-4","itemData":{"DOI":"10.1007/s10916-014-0025-1","ISBN":"1091601400251","ISSN":"1573689X","PMID":"24696394","abstract":"Wireless Capsule Endoscopy (WCE) is a technology in the field of endoscopic imaging which facilitates direct visualization of the entire small intestine. Many algorithms are being developed to automatically identify clinically important frames in WCE videos. This paper presents a supervised method for automated detection of bleeding regions present in WCE frames or images. The proposed method characterizes the image regions by using statistical features derived from the first order histogram probability of the three planes of RGB color space. Despite being inconsistent and tiresome, manual selection of regions has been a popular technique for creating training data in the studies of capsule endoscopic images. We propose a semi-automatic region-annotation algorithm for creating training data efficiently. All possible combinations of different features are exhaustively analyzed to find the optimum feature set with the best performance. During operation, regions from images are obtained by applying a segmentation method. Finally, a trained neural network recognizes the patterns of the data arising from bleeding and non-bleeding regions.","author":[{"dropping-particle":"","family":"Sainju","given":"Sonu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bui","given":"Francis M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wahid","given":"Khan A.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Medical Systems","id":"ITEM-4","issue":"4","issued":{"date-parts":[["2014"]]},"title":"Automated bleeding detection in capsule endoscopy videos using statistical features and region growing","type":"article-journal","volume":"38"},"uris":[""]},{"id":"ITEM-5","itemData":{"DOI":"10.1109/JBHI.2015.2399502","ISBN":"9781479969234","ISSN":"21682194","PMID":"25675468","abstract":"Wireless capsule endoscopy (WCE) enables non-invasive and painless direct visual inspection of a patient's whole digestive tract, but at the price of long time reviewing large amount of images by clinicians. Thus an automatic computer-aided technique to reduce the burden of physicians is highly demanded. In this paper, we propose a novel color feature extraction method to discriminate the bleeding frames from the normal ones, with further localization of the bleeding regions. Our proposal is based on a twofold system. First, we make full use of the color information of WCE images and utilize K-means clustering method on the pixel represented images to obtain the cluster centers, with which we characterize WCE images as words based color histograms. Then we judge the status of a WCE frame by applying support vector machine (SVM) and K nearest neighbor (KNN) methods. Comprehensive experimental results reveal that the best classification performance is obtained with YCbCr color space, cluster number 80 and the SVM. The achieved classification performance reaches 95.75% in accuracy, 0.9771 for AUC, validating that the proposed scheme provides an exciting performance for bleeding classification. Secondly, we propose a two-stage saliency map extraction method to highlight bleeding regions where the first stage saliency map is created by means of different color channels mixer and the second stage saliency map is obtained from the visual contrast. Followed by an appropriate fusion strategy and threshold, we localize the bleeding areas. Quantitative as well as qualitative results show that our methods could differentiate the bleeding areas from neighborhoods correctly.","author":[{"dropping-particle":"","family":"Yuan","given":"Yixuan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Li","given":"Baopu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Meng","given":"Max Q.H.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Journal of Biomedical and Health Informatics","id":"ITEM-5","issue":"2","issued":{"date-parts":[["2016"]]},"page":"624-630","title":"Bleeding Frame and Region Detection in the Wireless Capsule Endoscopy Video","type":"article-journal","volume":"20"},"uris":[""]},{"id":"ITEM-6","itemData":{"DOI":"10.1016/j.cmpb.2015.09.005","ISSN":"18727565","PMID":"26390947","abstract":"Background and objective: Wireless Capsule Endoscopy (WCE) can image the portions of the human gastrointestinal tract that were previously unreachable for conventional endoscopy examinations. A major drawback of this technology is that a large volume of data are to be analyzed in order to detect a disease which can be time-consuming and burdensome for the clinicians. Consequently, there is a dire need of computer-aided disease detection schemes to assist the clinicians. In this paper, we propose a real-time, computationally efficient and effective computerized bleeding detection technique applicable for WCE technology. Methods: The development of our proposed technique is based on the observation that characteristic patterns appear in the frequency spectrum of the WCE frames due to the presence of bleeding region. Discovering these discriminating patterns, we develop a texture-feature-descriptor-based-algorithm that operates on the Normalized Gray Level Co-occurrence Matrix (NGLCM) of the magnitude spectrum of the images. A new local texture descriptor called difference average that operates on NGLCM is also proposed. We also perform statistical validation of the proposed scheme. Results: The proposed algorithm was evaluated using a publicly available WCE database. The training set consisted of 600 bleeding and 600 non-bleeding frames. This set was used to train the SVM classifier. On the other hand, 860 bleeding and 860 non-bleeding images were selected from the rest of the extracted images to form the test set. The accuracy, sensitivity and specificity obtained from our method are 99.19%, 99.41% and 98.95% respectively which are significantly higher than state-of-the-art methods. In addition, the low computational cost of our method makes it suitable for real-time implementation. Conclusion: This work proposes a bleeding detection algorithm that employs textural features from the magnitude spectrum of the WCE images. Experimental outcomes backed by statistical validations prove that the proposed algorithm is superior to the existing ones in terms of accuracy, sensitivity, specificity and computational cost.","author":[{"dropping-particle":"","family":"Hassan","given":"Ahnaf Rashik","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Haque","given":"Mohammad Ariful","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Computer Methods and Programs in Biomedicine","id":"ITEM-6","issue":"3","issued":{"date-parts":[["2015"]]},"page":"341-353","publisher":"Elsevier Ireland Ltd","title":"Computer-aided gastrointestinal hemorrhage detection in wireless capsule endoscopy videos","type":"article-journal","volume":"122"},"uris":[""]},{"id":"ITEM-7","itemData":{"DOI":"10.1016/j.bspc.2017.10.011","ISSN":"17468108","abstract":"Capsule Endoscopy (CE) is a non-invasive clinical procedure that allows examination of the entire gastrointestinal tract including parts of small intestine beyond the scope of conventional endoscope. It requires computer-aided approach for the assessment of video frames to reduce diagnosis time. This paper presents a computer-assisted method based on a classifier fusion algorithm which combines two optimized Support Vector Machine (SVM) classifiers to automatically detect bleeding regions present in CE frames. The classifiers are based on RGB and HSV color spaces; the image regions are characterized on the basis of statistical features derived from the first-order histogram probability of respective color channels. A nested cross validation strategy has been adopted for the parameter tuning and feature selection to optimize the classifiers. The optimum feature sets for the best performance are evaluated after exhaustive analysis. The proposed fusion approach achieves an average accuracy of 95%, sensitivity of 94% and specificity of 95.3% for a dataset of 8872 CE frames, which is higher than that obtained from a single classifier. Comparison with the state-of-the-art algorithms exhibits that the proposed method yields superior performance for diverse dataset.","author":[{"dropping-particle":"","family":"Deeba","given":"Farah","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Islam","given":"Monzurul","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bui","given":"Francis M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wahid","given":"Khan A.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Biomedical Signal Processing and Control","id":"ITEM-7","issued":{"date-parts":[["2018"]]},"page":"415-424","publisher":"Elsevier Ltd","title":"Performance assessment of a bleeding detection algorithm for endoscopic video based on classifier fusion method and exhaustive feature selection","type":"article-journal","volume":"40"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>196–198,213–216</sup>","plainTextFormattedCitation":"196–198,213–216","previouslyFormattedCitation":"<sup>197–199,214–217</sup>"},"properties":{"noteIndex":0},"schema":""}196–198,213–216 receiving most attention as it is often an indication for many GI disorders, such as CRC and Crohn’s diseaseADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/RBME.2011.2175445","ISBN":"1941-1189","ISSN":"19373333","PMID":"22273792","abstract":"Today, medical endoscopy is a widely used procedure to inspect the inner cavities of the human body. The advent of endoscopic imaging techniques-allowing the acquisition of images or videos-created the possibility for the development of the whole new branch of computer-aided decision support systems. Such systems aim at helping physicians to identify possibly malignant abnormalities more accurately. At the beginning of this paper, we give a brief introduction to the history of endoscopy, followed by introducing the main types of endoscopes which emerged so far (flexible endoscope, wireless capsule endoscope, and confocal laser endomicroscope). We then give a brief introduction to computer-aided decision support systems specifically targeted at endoscopy in the gastrointestinal tract. Then we present general facts and figures concerning computer-aided decision support systems and summarize work specifically targeted at computer-aided decision support in the gastrointestinal tract. This summary is followed by a discussion of some common issues concerning the approaches reviewed and suggestions of possible ways to resolve them.","author":[{"dropping-particle":"","family":"Liedlgruber","given":"Michael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Uhl","given":"Andreas","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Reviews in Biomedical Engineering","id":"ITEM-1","issued":{"date-parts":[["2011"]]},"page":"73-88","title":"Computer-aided decision support systems for endoscopy in the gastrointestinal tract: A review","type":"article-journal","volume":"4"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>217</sup>","plainTextFormattedCitation":"217","previouslyFormattedCitation":"<sup>218</sup>"},"properties":{"noteIndex":0},"schema":""}217. Some studies have begun to address the identification of more than a single abnormality, with methods reported for simultaneous detection of small bowel ulcers and polypsADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/TBME.2011.2155064","ISBN":"9781424439324","ISSN":"00189294","PMID":"21592915","abstract":"Over the last decade, wireless capsule endoscopy (WCE) technology has become a very useful tool for diagnosing diseases within the human digestive tract. Physicians using WCE can examine the digestive tract in a minimally invasive way searching for pathological abnormalities such as bleeding, polyps, ulcers, and Crohn's disease. To improve effectiveness of WCE, researchers have developed software methods to automatically detect these diseases at a high rate of success. This paper proposes a novel synergistic methodology for automatically discovering polyps (protrusions) and perforated ulcers in WCE video frames. Finally, results of the methodology are given and statistical comparisons are also presented relevant to other works.","author":[{"dropping-particle":"","family":"Karargyris","given":"Alexandros","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bourbakis","given":"Nikolaos","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Transactions on Biomedical Engineering","id":"ITEM-1","issue":"10 PART 1","issued":{"date-parts":[["2011"]]},"page":"2777-2786","title":"Detection of small bowel polyps and ulcers in wireless capsule endoscopy videos","type":"article-journal","volume":"58"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>218</sup>","plainTextFormattedCitation":"218","previouslyFormattedCitation":"<sup>219</sup>"},"properties":{"noteIndex":0},"schema":""}218 and of gastrointestinal bleeding and ulcersADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.cmpb.2012.09.004","ISBN":"1872-7565 (Electronic)\\r0169-2607 (Linking)","ISSN":"01692607","PMID":"23164524","abstract":"This paper presents an in-depth study of several approaches to exploratory analysis of wireless capsule endoscopy images (WCE). It is demonstrated that versatile texture and color based descriptors of image regions corresponding to various anomalies of the gastrointestinal tract allows their accurate detection of pathologies in a sequence of WCE frames. Moreover, through classification of single pixels described by texture features of their neighborhood, the images can be segmented into homogeneous areas well matched to the image content. For both, detection and segmentation tasks the same procedure is applied which consists of features calculation, relevant feature subset selection and classification stages. This general three-stage framework is realized using various recognition strategies. In particular, the performance of the developed Vector Supported Convex Hull classification algorithm is compared against Support Vector Machines run in configuration with two different feature selection methods. ? 2012 Elsevier Ireland Ltd.","author":[{"dropping-particle":"","family":"Szczypiński","given":"Piotr","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Klepaczko","given":"Artur","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pazurek","given":"Marek","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Daniel","given":"Piotr","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Computer Methods and Programs in Biomedicine","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2014"]]},"page":"396-411","title":"Texture and color based image segmentation and pathology detection in capsule endoscopy videos","type":"article-journal","volume":"113"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>219</sup>","plainTextFormattedCitation":"219","previouslyFormattedCitation":"<sup>220</sup>"},"properties":{"noteIndex":0},"schema":""}219 . This task is not trivial, as demonstrated in the study by GanADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.3748/wjg.14.6929","ISBN":"8628854223","ISSN":"10079327","PMID":"19058327","abstract":"AIM: To investigate and evaluate the feasibility of the computer-aided screening diagnosis for enteric lesions in the capsule endoscopy (CE). METHODS: After developing a series of algorithms for the screening diagnosis of the enteric lesions in CE based on their characteristic colors and contours, the normal and abnormal images obtained from 289 patients were respectively scanned and diagnosed by the CE readers and by the computer-aided screening for the enteric lesions with the image-processed software (IPS). The enteric lesions shown by the images included esoenteritis, mucosal ulcer and erosion, bleeding, space-occupying lesions, angioectasia, diverticula, parasites, etc. The images for the lesions or the suspected lesions confirmed by the CE readers and the computers were collected, and the effectiveness rate of the screening and the number of the scanned images were evaluated, respectively. RESULTS: Compared with the diagnostic results obtained by the CE readers, the total effectiveness rate (sensitivity) in the screening of the commonly-encountered enteric lesions by IPS varied from 42.9% to 91.2%, with a median of 74.2%, though the specificity and the accuracy rates were still low, and the images for the rarely-encountered lesions were difficult to differentiate from the normal images. However, the number of the images screened by IPS was 5000 on average, and only 10%-15% of the original images were left behind. As a result, a large number of normal images were excluded, and the reading time decreased from 5 h to 1 h on average. CONCLUSION: Though the total accuracy and specificity rates by the computer-aided screening for the enteric lesions with IPS are much lower than those by the CE readers, the computer-aided screening diagnosis can exclude a large number of the normal images and confine the enteric lesions to 5000 images on average, which can reduce the workload of the readers in the scanning of the images. This computer-aided screening technique can make a correct diagnosis as efficiently as possible in most of the patients.","author":[{"dropping-particle":"","family":"Gan","given":"Tao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wu","given":"Jun Chao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rao","given":"Ni Ni","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chen","given":"Tao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Liu","given":"Bing","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"World Journal of Gastroenterology","id":"ITEM-1","issue":"45","issued":{"date-parts":[["2008"]]},"page":"6929-6935","title":"A feasibility trial of computer-aided diagnosis for enteric lesions in capsule endoscopy","type":"article-journal","volume":"14"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>203</sup>","plainTextFormattedCitation":"203","previouslyFormattedCitation":"<sup>204</sup>"},"properties":{"noteIndex":0},"schema":""}203, which illustrated the varying accuracy of an algorithm based on the separation and identification of suspected enteric lesions by their associated colors in correctly identifying different types of enteric lesions because of the complexity and diverse multiformity. Comparing the effectiveness of these proposed methods of CADx to each other in detail is difficult owing to the lack of standardized datasets of CE images. The reported accuracy, sensitivity and specificity of some of the studies found in the literature are shown in REF _Ref397784843 \h Table 4, although accurate comparison of these algorithms is limited due to the lack of standardized data sets. .To date, nNo studies have been performed to date on the use of CADx in conjunction with capsule modalities other than WLI because of the limited number of non-WLI CE devices available. However, initial studies on the use of CADx with non-capsule based endoscopy has been conducted using modalities such as OCTADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1364/BOE.2.002821","ISSN":"2156-7085","PMID":"22091441","abstract":"The impact of digestive diseases, which include disorders affecting the oropharynx and alimentary canal, ranges from the inconvenience of a transient diarrhoea to dreaded conditions such as pancreatic cancer, which are usually fatal. Currently, the major limitation for the diagnosis of such diseases is sampling error because, even in the cases of rigorous adherence to biopsy protocols, only a tiny fraction of the surface of the involved gastrointestinal tract is sampled. Optical coherence tomography (OCT), which is an interferometric imaging technique for the minimally invasive measurement of biological samples, could decrease sampling error, increase yield, and even eliminate the need for tissue sampling provided that an automated, quick and reproducible tissue classification system is developed. Segmentation and quantification of ophthalmologic pathologies using OCT traditionally rely on the extraction of thickness and size measures from the OCT images, but layers are often not observed in nonopthalmic OCT imaging. Distinct mathematical methods, namely Principal Component Analysis (PCA) and textural analyses including both spatial textural analysis derived from the two-dimensional discrete Fourier transform (DFT) and statistical texture analysis obtained independently from center-symmetric autocorrelation (CSAC) and spatial grey-level dependency matrices (SGLDM), have been previously reported to overcome this problem. We propose an alternative approach consisting of a region segmentation according to the intensity variation along the vertical axis and a pure statistical technique for feature quantification, i.e. morphological analysis. Qualitative and quantitative comparisons with traditional approaches are accomplished in the discrimination of freshly-excised specimens of gastrointestinal tissues to exhibit the feasibility of the proposed method for computer-aided diagnosis (CAD) in the clinical setting.","author":[{"dropping-particle":"","family":"Garcia-Allende","given":"P. Beatriz","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Amygdalos","given":"Iakovos","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dhanapala","given":"Hiruni","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Goldin","given":"Robert D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hanna","given":"George B.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Elson","given":"Daniel S.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Biomedical Optics Express","id":"ITEM-1","issue":"10","issued":{"date-parts":[["2011"]]},"page":"2821","title":"Morphological analysis of optical coherence tomography images for automated classification of gastrointestinal tissues","type":"article-journal","volume":"2"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1364/BOE.7.000409","ISSN":"2156-7085","author":[{"dropping-particle":"","family":"Ughi","given":"Giovanni J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gora","given":"Michalina J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Swager","given":"Anne-Fré","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Soomro","given":"Amna","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Grant","given":"Catriona","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tiernan","given":"Aubrey","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rosenberg","given":"Mireille","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sauk","given":"Jenny S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nishioka","given":"Norman S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tearney","given":"Guillermo J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Biomedical Optics Express","id":"ITEM-2","issue":"2","issued":{"date-parts":[["2016","2","1"]]},"page":"409","title":"Automated segmentation and characterization of esophageal wall in vivo by tethered capsule optical coherence tomography endomicroscopy","type":"article-journal","volume":"7"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1117/1.JBO.22.12.121716","ISSN":"1083-3668","PMID":"29260538","author":[{"dropping-particle":"","family":"Tsai","given":"Tsung-Han","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leggett","given":"Cadman L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Trindade","given":"Arvind J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Biomedical Optics","id":"ITEM-3","issue":"12","issued":{"date-parts":[["2017"]]},"page":"1","title":"Optical coherence tomography in gastroenterology: a review and future outlook","type":"article-journal","volume":"22"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>220–222</sup>","plainTextFormattedCitation":"220–222","previouslyFormattedCitation":"<sup>221–223</sup>"},"properties":{"noteIndex":0},"schema":""}220–222, autofluorescenceADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.3748/wjg.v19.i41.7146","ISBN":"1007-9327 (Print)\\n1007-9327 (Linking)","ISSN":"10079327","PMID":"24222959","abstract":"AIM: To evaluate the efficacy of computer-assisted color analysis of colorectal lesions using a novel auto-fluorescence imaging (AFI) system to distinguish neoplastic lesions from non-neoplastic lesions and to predict the depth of invasion. METHODS: From January 2013 to April 2013, consecutive patients with known polyps greater than 5 mm in size who were scheduled to undergo endoscopic treatment at The Jikei University Hospital were prospectively recruited for this study. All lesions were evaluated using a novel AFI system, and color-tone sampling was performed in a region of interest determined from narrow band imaging or from chromoendoscopy findings without magnification. The green/red (G/R) ratio for each lesion on the AFI images was calculated automatically using a computer-assisted color analysis system that permits real-time color analysis during endoscopic procedures. RESULTS: A total of 88 patients with 163 lesions were enrolled in this study. There were significant differences in the G/R ratios of hyperplastic polyps (non-neoplastic lesions), adenoma/intramucosal cancer/submucosal (SM) superficial cancer, and SM deep cancer (P < 0.0001). The mean ± SD G/R ratios were 0.984 ± 0.118 in hyperplastic polyps and 0.827 ± 0.081 in neoplastic lesions. The G/R ratios of hyperplastic polyps were significantly higher than those of neoplastic lesions (P < 0.001). When a G/R ratio cut-off value of > 0.89 was applied to determine non-neoplastic lesions, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 83.9%, 82.6%, 53.1%, 95.6% and 82.8%, respectively. For neoplastic lesions, the mean G/R ratio was 0.834 ± 0.080 in adenoma/intramucosal cancer/SM superficial cancer and 0.746 ± 0.045 in SM deep cancer. The G/R ratio of adenoma/intramucosal cancer/SM superficial cancer was significantly higher than that of SM deep cancer (P < 0.01). When a G/R ratio cut-off value of < 0.77 was applied to distinguish SM deep cancers, the sensitivity, specificity, PPV, NPV, and accuracy were 80.0%, 84.4%, 29.6%, 98.1% and 84.1%, respectively. CONCLUSION: The novel AFI system with color analysis was effective in distinguishing non-neoplastic lesions from neoplastic lesions and might allow determination of the depth of invasion.","author":[{"dropping-particle":"","family":"Inomata","given":"Hiroko","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tamai","given":"Naoto","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Aihara","given":"Hiroyuki","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sumiyama","given":"Kazuki","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Saito","given":"Shoichi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kato","given":"Tomohiro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tajiri","given":"Hisao","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"World Journal of Gastroenterology","id":"ITEM-1","issue":"41","issued":{"date-parts":[["2013"]]},"page":"7146-7153","title":"Efficacy of a novel auto-fluorescence imaging system with computer-assisted color analysis for assessment of colorectal lesions","type":"article-journal","volume":"19"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>223</sup>","plainTextFormattedCitation":"223","previouslyFormattedCitation":"<sup>224</sup>"},"properties":{"noteIndex":0},"schema":""}223 and narrow band imagingNBIADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.gie.2017.11.029","ISSN":"10976779","PMID":"29225083","abstract":"Background and Aims: Magnifying narrow-band imaging (M-NBI) is important in the diagnosis of early gastric cancers (EGCs) but requires expertise to master. We developed a computer-aided diagnosis (CADx) system to assist endoscopists in identifying and delineating EGCs. Methods: We retrospectively collected and randomly selected 66 EGC M-NBI images and 60 non-cancer M-NBI images into a training set and 61 EGC M-NBI images and 20 non-cancer M-NBI images into a test set. After preprocessing and partition, we determined 8 gray-level co-occurrence matrix (GLCM) features for each partitioned 40 × 40 pixel block and calculated a coefficient of variation of 8 GLCM feature vectors. We then trained a support vector machine (SVMLv1) based on variation vectors from the training set and examined in the test set. Furthermore, we collected 2 determined P and Q GLCM feature vectors from cancerous image blocks containing irregular microvessels from the training set, and we trained another SVM (SVMLv2) to delineate cancerous blocks, which were compared with expert-delineated areas for area concordance. Results: The diagnostic performance revealed accuracy of 96.3%, precision (positive predictive value [PPV]) of 98.3%, recall (sensitivity) of 96.7%, and specificity of 95%, at a rate of 0.41 ± 0.01 seconds per image. The performance of area concordance, on a block basis, demonstrated accuracy of 73.8% ± 10.9%, precision (PPV) of 75.3% ± 20.9%, recall (sensitivity) of 65.5% ± 19.9%, and specificity of 80.8% ± 17.1%, at a rate of 0.49 ± 0.04 seconds per image. Conclusions: This pilot study demonstrates that our CADx system has great potential in real-time diagnosis and delineation of EGCs in M-NBI images.","author":[{"dropping-particle":"","family":"Kanesaka","given":"Takashi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lee","given":"Tsung Chun","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Uedo","given":"Noriya","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lin","given":"Kun Pei","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chen","given":"Huai Zhe","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lee","given":"Ji Yuh","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wang","given":"Hsiu Po","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chang","given":"Hsuan Ting","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastrointestinal Endoscopy","id":"ITEM-1","issue":"5","issued":{"date-parts":[["2018"]]},"page":"1339-1344","publisher":"Elsevier, Inc.","title":"Computer-aided diagnosis for identifying and delineating early gastric cancers in magnifying narrow-band imaging","type":"article-journal","volume":"87"},"uris":[""]},{"id":"ITEM-2","itemData":{"ISBN":"9781479923496","author":[{"dropping-particle":"","family":"Gadermayr","given":"M","non-dropping-particle":"","parse-names":false,"suffix":""}],"id":"ITEM-2","issued":{"date-parts":[["2016"]]},"page":"355-359","title":"NARROW BAND IMAGING VERSUS WHITE-LIGHT : WHAT IS BEST FOR COMPUTER-ASSISTED DIAGNOSIS OF CELIAC DISEASE ? Institute of Imaging and Computer Vision , RWTH Aachen , Germany Department of Computer Sciences , University of Salzburg , Austria St . Anna Childre","type":"article-journal"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1016/j.gie.2011.08.051","ISBN":"1097-6779 (Electronic)\\r0016-5107 (Linking)","ISSN":"00165107","PMID":"22196816","abstract":"Narrow-band imaging (NBI) classification of colorectal lesions is clinically useful in determining treatment options for colorectal tumors. There is a learning curve, however. Accurate NBI-based diagnosis requires training and experience. In addition, objective diagnosis is necessary. Thus, we developed a computerized system to automatically classify NBI magnifying colonoscopic images. To evaluate the utility and limitations of our automated NBI classification system. Retrospective study. Department of endoscopy, university hospital. Performance of our computer-based system for classification of NBI magnifying colonoscopy images in comparison to classification by two experienced endoscopists and to histologic findings. For the 371 colorectal lesions depicted on validation images, the computer-aided classification system yielded a detection accuracy of 97.8% (363/371); sensitivity and specificity of types B-C3 lesions for a diagnosis of neoplastic lesion were 97.8% (317/324) and 97.9% (46/47), respectively. Diagnostic concordance between the computer-aided classification system and the two experienced endoscopists was 98.7% (366/371), with no significant difference between methods. Retrospective, single-center in this initial report. Our new computer-aided system is reliable for predicting the histology of colorectal tumors by using NBI magnifying colonoscopy. ? 2012 American Society for Gastrointestinal Endoscopy.","author":[{"dropping-particle":"","family":"Takemura","given":"Yoshito","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yoshida","given":"Shigeto","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tanaka","given":"Shinji","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kawase","given":"Rie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Onji","given":"Keiichi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Oka","given":"Shiro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tamaki","given":"Toru","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Raytchev","given":"Bisser","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kaneda","given":"Kazufumi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yoshihara","given":"Masaharu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chayama","given":"Kazuaki","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastrointestinal Endoscopy","id":"ITEM-3","issue":"1","issued":{"date-parts":[["2012"]]},"page":"179-185","publisher":"Elsevier Inc.","title":"Computer-aided system for predicting the histology of colorectal tumors by using narrow-band imaging magnifying colonoscopy (with video)","type":"article-journal","volume":"75"},"uris":[""]},{"id":"ITEM-4","itemData":{"DOI":"10.1016/j.media.2012.08.003","ISBN":"1361-8423 (Electronic)\\n1361-8415 (Linking)","ISSN":"13618415","PMID":"23085199","abstract":"An early detection of colorectal cancer through colorectal endoscopy is important and widely used in hospitals as a standard medical procedure. During colonoscopy, the lesions of colorectal tumors on the colon surface are visually inspected by a Narrow Band Imaging (NBI) zoom-videoendoscope. By using the visual appearance of colorectal tumors in endoscopic images, histological diagnosis is presumed based on classification schemes for NBI magnification findings. In this paper, we report on the performance of a recognition system for classifying NBI images of colorectal tumors into three types (A, B, and C3) based on the NBI magnification findings. To deal with the problem of computer-aided classification of NBI images, we explore a local feature-based recognition method, bag-of-visual-words (BoW), and provide extensive experiments on a variety of technical aspects. The proposed prototype system, used in the experiments, consists of a bag-of-visual-words representation of local features followed by Support Vector Machine (SVM) classifiers. A number of local features are extracted by using sampling schemes such as Difference-of-Gaussians and grid sampling. In addition, in this paper we propose a new combination of local features and sampling schemes. Extensive experiments with varying the parameters for each component are carried out, for the performance of the system is usually affected by those parameters, e.g. the sampling strategy for the local features, the representation of the local feature histograms, the kernel types of the SVM classifiers, the number of classes to be considered, etc. The recognition results are compared in terms of recognition rates, precision/recall, and F-measure for different numbers of visual words. The proposed system achieves a recognition rate of 96% for 10-fold cross validation on a real dataset of 908 NBI images collected during actual colonoscopy, and 93% for a separate test dataset. ? 2012 Elsevier B.V.","author":[{"dropping-particle":"","family":"Tamaki","given":"Toru","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yoshimuta","given":"Junki","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kawakami","given":"Misato","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Raytchev","given":"Bisser","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kaneda","given":"Kazufumi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yoshida","given":"Shigeto","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Takemura","given":"Yoshito","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Onji","given":"Keiichi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Miyaki","given":"Rie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tanaka","given":"Shinji","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Medical Image Analysis","id":"ITEM-4","issue":"1","issued":{"date-parts":[["2013"]]},"page":"78-100","publisher":"Elsevier B.V.","title":"Computer-aided colorectal tumor classification in NBI endoscopy: Using local features","type":"article-journal","volume":"17"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>224–227</sup>","plainTextFormattedCitation":"224–227","previouslyFormattedCitation":"<sup>225–228</sup>"},"properties":{"noteIndex":0},"schema":""}224–227. A study comprised of 88 patients with 163 lesions to assess the efficacy of color analysis of AFI endoscopy images in the computer-aided differentiation of intramucosal lesions and superficial submucosal cancer from submucosal deep cancer. This method demonstrated sensitivity, specificity and accuracy of 80.0%, 84.4% and 84.1% respectivelyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.3748/wjg.v19.i41.7146","ISBN":"1007-9327 (Print)\\n1007-9327 (Linking)","ISSN":"10079327","PMID":"24222959","abstract":"AIM: To evaluate the efficacy of computer-assisted color analysis of colorectal lesions using a novel auto-fluorescence imaging (AFI) system to distinguish neoplastic lesions from non-neoplastic lesions and to predict the depth of invasion. METHODS: From January 2013 to April 2013, consecutive patients with known polyps greater than 5 mm in size who were scheduled to undergo endoscopic treatment at The Jikei University Hospital were prospectively recruited for this study. All lesions were evaluated using a novel AFI system, and color-tone sampling was performed in a region of interest determined from narrow band imaging or from chromoendoscopy findings without magnification. The green/red (G/R) ratio for each lesion on the AFI images was calculated automatically using a computer-assisted color analysis system that permits real-time color analysis during endoscopic procedures. RESULTS: A total of 88 patients with 163 lesions were enrolled in this study. There were significant differences in the G/R ratios of hyperplastic polyps (non-neoplastic lesions), adenoma/intramucosal cancer/submucosal (SM) superficial cancer, and SM deep cancer (P < 0.0001). The mean ± SD G/R ratios were 0.984 ± 0.118 in hyperplastic polyps and 0.827 ± 0.081 in neoplastic lesions. The G/R ratios of hyperplastic polyps were significantly higher than those of neoplastic lesions (P < 0.001). When a G/R ratio cut-off value of > 0.89 was applied to determine non-neoplastic lesions, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 83.9%, 82.6%, 53.1%, 95.6% and 82.8%, respectively. For neoplastic lesions, the mean G/R ratio was 0.834 ± 0.080 in adenoma/intramucosal cancer/SM superficial cancer and 0.746 ± 0.045 in SM deep cancer. The G/R ratio of adenoma/intramucosal cancer/SM superficial cancer was significantly higher than that of SM deep cancer (P < 0.01). When a G/R ratio cut-off value of < 0.77 was applied to distinguish SM deep cancers, the sensitivity, specificity, PPV, NPV, and accuracy were 80.0%, 84.4%, 29.6%, 98.1% and 84.1%, respectively. CONCLUSION: The novel AFI system with color analysis was effective in distinguishing non-neoplastic lesions from neoplastic lesions and might allow determination of the depth of invasion.","author":[{"dropping-particle":"","family":"Inomata","given":"Hiroko","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tamai","given":"Naoto","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Aihara","given":"Hiroyuki","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sumiyama","given":"Kazuki","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Saito","given":"Shoichi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kato","given":"Tomohiro","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tajiri","given":"Hisao","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"World Journal of Gastroenterology","id":"ITEM-1","issue":"41","issued":{"date-parts":[["2013"]]},"page":"7146-7153","title":"Efficacy of a novel auto-fluorescence imaging system with computer-assisted color analysis for assessment of colorectal lesions","type":"article-journal","volume":"19"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>223</sup>","plainTextFormattedCitation":"223","previouslyFormattedCitation":"<sup>224</sup>"},"properties":{"noteIndex":0},"schema":""}223. Initial work by Garcia-Allende et al. on excised gastrointestinal tissue found that automated morphological analysis of OCT images had sensitivity, specificity and accuracy as high as 99.7%, 99.85% and 99.88%, respectively, for identifying tumour tissue ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1364/BOE.2.002821","ISSN":"2156-7085","PMID":"22091441","abstract":"The impact of digestive diseases, which include disorders affecting the oropharynx and alimentary canal, ranges from the inconvenience of a transient diarrhoea to dreaded conditions such as pancreatic cancer, which are usually fatal. Currently, the major limitation for the diagnosis of such diseases is sampling error because, even in the cases of rigorous adherence to biopsy protocols, only a tiny fraction of the surface of the involved gastrointestinal tract is sampled. Optical coherence tomography (OCT), which is an interferometric imaging technique for the minimally invasive measurement of biological samples, could decrease sampling error, increase yield, and even eliminate the need for tissue sampling provided that an automated, quick and reproducible tissue classification system is developed. Segmentation and quantification of ophthalmologic pathologies using OCT traditionally rely on the extraction of thickness and size measures from the OCT images, but layers are often not observed in nonopthalmic OCT imaging. Distinct mathematical methods, namely Principal Component Analysis (PCA) and textural analyses including both spatial textural analysis derived from the two-dimensional discrete Fourier transform (DFT) and statistical texture analysis obtained independently from center-symmetric autocorrelation (CSAC) and spatial grey-level dependency matrices (SGLDM), have been previously reported to overcome this problem. We propose an alternative approach consisting of a region segmentation according to the intensity variation along the vertical axis and a pure statistical technique for feature quantification, i.e. morphological analysis. Qualitative and quantitative comparisons with traditional approaches are accomplished in the discrimination of freshly-excised specimens of gastrointestinal tissues to exhibit the feasibility of the proposed method for computer-aided diagnosis (CAD) in the clinical setting.","author":[{"dropping-particle":"","family":"Garcia-Allende","given":"P. Beatriz","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Amygdalos","given":"Iakovos","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dhanapala","given":"Hiruni","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Goldin","given":"Robert D.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hanna","given":"George B.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Elson","given":"Daniel S.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Biomedical Optics Express","id":"ITEM-1","issue":"10","issued":{"date-parts":[["2011"]]},"page":"2821","title":"Morphological analysis of optical coherence tomography images for automated classification of gastrointestinal tissues","type":"article-journal","volume":"2"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>220</sup>","plainTextFormattedCitation":"220","previouslyFormattedCitation":"<sup>221</sup>"},"properties":{"noteIndex":0},"schema":""}220. Subsequent in vivo studies by Ughi et al. used a tethered capsule-like device to identify Barrett’s esophagusoesophagus on human volunteers. Results showed sensitivity, specificity and accuracy of 94%, 93% and 94%, respectively. However, the study population was limited with one healthy control and two with esophagealoesophageal abnormalitiesADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1364/BOE.7.000409","ISSN":"2156-7085","author":[{"dropping-particle":"","family":"Ughi","given":"Giovanni J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gora","given":"Michalina J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Swager","given":"Anne-Fré","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Soomro","given":"Amna","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Grant","given":"Catriona","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tiernan","given":"Aubrey","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rosenberg","given":"Mireille","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sauk","given":"Jenny S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nishioka","given":"Norman S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tearney","given":"Guillermo J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Biomedical Optics Express","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2016","2","1"]]},"page":"409","title":"Automated segmentation and characterization of esophageal wall in vivo by tethered capsule optical coherence tomography endomicroscopy","type":"article-journal","volume":"7"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>221</sup>","plainTextFormattedCitation":"221","previouslyFormattedCitation":"<sup>222</sup>"},"properties":{"noteIndex":0},"schema":""}221. These studies demonstrate that CADx has the potential to be used with specific non-WLI modalities to detect various gastrointestinal pathologies.[H1]ConclusionsLooking ahead, several issues need to be addressed to translate this nascent research in non-white light imaging CE into wider clinical practice (Box 1). Many CE devices are being developed with various imaging and sensing modalities to overcome the limitations of WLI, but these are still in early stages of development with many yet to undergo in vivo animal and human trials. Furthermore, the clinical efficacy of the devices that have been used in humans still needs to be verified as the studies conducted to date are typically limited by small sample sizes. Large clinical trials are required to ascertain the diagnostic yield of these non-WLI capsules for various pathologies. The specialization of CE, already seen to some extent with WLI CE devices modified to perform better in different parts of the GI tract, will probably continue. By combining multiple modalities within a single device, the diagnostic potential will be increased beyond what can be achieved with single modality devices. A multimodal approach will facilitate both CADx, as already observed with conventional endoscopy, and virtual biopsy by improving accuracy, sensitivity and specificity. However, the combination of modalities for the diagnosis of specific gastrointestinal diseases still needs to be determined. Other technical challenges include improved localization, which is crucial for virtual biopsy to enable accurate, regular monitoring of pathology. AcknowledgementsThis work was supported by the UK Engineering and Physical Sciences Research Council under the Grant EP/K034537/1, entitled Sonopill and by the European Commission within the framework of the endoscopic versatile robotic guidance, diagnosis and therapy of magnetic-driven soft-tethered endoluminal robots Project-H2020-ICT-24-2015 (EU Project-G.A. number: 688592). The authors wish to acknowledge the support of Mr Vasileios Mitrakos in reviewing this manuscript. 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The efficiency of the PillCam SB2 (Given Imaging) has been widely reported. The CapsoCam capsule (Capso- vision) has four cameras allowing the exploration of the small bowel through 360° lateral viewing. This system does not include a recording system so the capsule has to be retrieved by the patient after expulsion in order for the film to be down- loaded. The aim of this study was to evaluate di- agnostic concordance (kappa value) of the Pill- Cam SB2 and CapsoCam capsules in the same pa- tients. Methods: This was a prospective comparative study in four French referral endoscopy units. Consecutive patients ingested the two capsules 1 hour apart and in a randomized order. Results: In the 73 included patients therewere 13 technical issues (11 CapsoCam, 2 PillCam SB2). Of the 60 patients with analyzable data, and follow- ing expert reviewof all discordant cases, a concor- dant positive diagnosiswas obtained in 23 (38.3%) and a negative diagnosiswas obtained and 26 pa- tients (43.3%). Concordancewas good, with a kap- pa value of 0.63 in analyzable patients, and 46.7% diagnosis with CapsoCam vs. 48.3% with PillCam SB2.CapsoCam and PillCam SB2 procedures iden- tified 81.8% (27/33) and 84.8% (28/33) of positive patients, respectively (P=0.791). In a per lesion a- nalysis, the CapsoCam capsule detected signifi- cantly more lesions (108 vs. 85 lesions; P=0.001). Reading time was longer for CapsoCam proce- dures (32.0 vs. 26.2 minutes; P=0.002). 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The Guideline was also reviewed and endorsed by the British Society of Gastroenterology (BSG). It addresses the roles of small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders. Main recommendations 1 ESGE recommends small-bowel video capsule endoscopy as the first-line investigation in patients with obscure gastrointestinal bleeding (strong recommendation, moderate quality evidence). 2 In patients with overt obscure gastrointestinal bleeding, ESGE recommends performing small-bowel capsule endoscopy as soon as possible after the bleeding episode, optimally within 14 days, in order to maximize the diagnostic yield (strong recommendation, moderate quality evidence). 3 ESGE does not recommend the routine performance of second-look endoscopy prior to small-bowel capsule endoscopy; however whether to perform second-look endoscopy before capsule endoscopy in patients with obscure gastrointestinal bleeding or iron-deficiency anaemia should be decided on a case-by-case basis (strong recommendation, low quality evidence). 4 In patients with positive findings at small-bowel capsule endoscopy, ESGE recommends device-assisted enteroscopy to confirm and possibly treat lesions identified by capsule endoscopy (strong recommendation, high quality evidence). 5 ESGE recommends ileocolonoscopy as the first endoscopic examination for investigating patients with suspected Crohn's disease (strong recommendation, high quality evidence). In patients with suspected Crohn's disease and negative ileocolonoscopy findings, ESGE recommends small-bowel capsule endoscopy as the initial diagnostic modality for investigating the small bowel, in the absence of obstructive symptoms or known stenosis (strong recommendation, moderate quality evidence).ESGE does not recommend routine small-bowel imaging or the use of the PillCam patency capsule prior to capsule endoscopy in these patients (strong recommendation, low quality evidence). In the presence of obstructive symptoms or known stenosis, ESGE recommends that dedicated small bowel cross-sectional imaging modalities such as magnetic resonance enterography/enteroclysis or computed tomography enterography/enteroclysis should be used first (strong recommendation, low quality evidence). 6 In patients with established Crohn's disease, based on ileocolonoscopy findings, ESGE recommends 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The aim of this consensus was to provide guidance on the appropriate use of CE in clinical practice. Methods A systematic literature search identified studies on the use of CE in patients with Crohn's disease, celiac disease, gastrointestinal bleeding, and anemia. The quality of evidence and strength of recommendations were rated using the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Results The consensus includes 21 statements focused on the use of small-bowel CE and colon capsule endoscopy. CE was recommended for patients with suspected, known, or relapsed Crohn's disease when ileocolonoscopy and imaging studies were negative if it was imperative to know whether active Crohn's disease was present in the small bowel. It was not recommended in patients with chronic abdominal pain or diarrhea, in whom there was no evidence of abnormal biomarkers typically associated with Crohn's disease. CE was recommended to assess patients with celiac disease who have unexplained symptoms despite appropriate treatment, but not to make the diagnosis. In patients with overt gastrointestinal bleeding, and negative findings on esophagogastroduodenoscopy and colonoscopy, CE should be performed as soon as possible. CE was recommended only in selected patients with unexplained, mild, chronic iron-deficiency anemia. CE was suggested for surveillance in patients with polyposis syndromes or other small-bowel cancers, who required small-bowel studies. Colon capsule endoscopy should not be substituted routinely for colonoscopy. Patients should be made aware of the potential risks of CE including a failed procedure, capsule retention, or a missed lesion. Finally, standardized criteria for training and reporting in CE should be defined. Conclusions CE generally should be considered a complementary test in patients with gastrointestinal bleeding, Crohn's disease, or celiac disease, who have had negative or inconclusive endoscopic or imaging studies.","author":[{"dropping-particle":"","family":"Enns","given":"Robert A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hookey","given":"Lawrence","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Armstrong","given":"David","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bernstein","given":"Charles N.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Heitman","given":"Steven J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Teshima","given":"Christopher","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Leontiadis","given":"Grigorios I.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tse","given":"Frances","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sadowski","given":"Daniel","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastroenterology","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2017","2"]]},"page":"497-514","publisher":"Elsevier","title":"Clinical Practice Guidelines for the Use of Video Capsule Endoscopy","type":"article-journal","volume":"152"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>6</sup>","plainTextFormattedCitation":"6","previouslyFormattedCitation":"<sup>6</sup>"},"properties":{"noteIndex":0},"schema":""}6Key guidance on the use of CERecommendationEvidence qualityKey guidance on the use of CERecommendationEvidence qualityOGIBFirst-line for investigation of OGIB.StrongModeratePerform CE as soon as possible for overt, OGIB episode.Strong Very low Recommended for selected cases with OGIB and unexplained mild chronic IDA.Strong LowIDAFirst-line for (IDA) following inconclusive results from conventional endoscopy.StrongModerateIncluded under OGIBSmall bowel tumourRecommended when OGIB and IDA are unexplained.StrongModerateNA NANAPolyposis syndromesFor surveillance of small bowel in patients with Familial adenomatous polyposis and Peutz-Jeghers syndrome.StrongModerateFor ongoing surveillance of small bowel in patients with polyposis syndromes.ConditionalVery low CeliacCoeliac diseaseNot recommended for suspected celiaccoeliac disease. Can be considered in patients unable or unwilling to undergo conventional endoscopy.Strong Low Not recommended for suspected celiaccoeliac disease. Can be considered in patients unable or unwilling to undergo conventional endoscopy.Strong Very low Crohn’s diseaseRecommended for suspected Crohn’s disease with negative ileocolonoscopy findings and absence of obstructive symptoms.StrongModerateRecommended for suspected Crohn’s disease with negative ileocolonoscopy findings and absence of obstructive symptoms.Strong Very low colorectal cancerCE can be considered in patients for whom conventional endoscopy is inappropriate or not possible. Grade D*Level 4CE can be considered in patients for whom conventional endoscopy is inappropriate or not possible. 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The engineering requirements to minimise these threats results in an extremely heavy and cumbersome clothing ensemble that increases the internal heat generation of the wearer, while the clothing's thermal properties reduce heat dissipation. This study aimed to evaluate the heat strain encountered wearing EOD protective clothing in simulated environmental extremes across a range of differing work intensities. Eight healthy males [age 25 ± 6 years (mean ± sd), height 180 ± 7 cm, body mass 79 ± 9 kg, VO2max 57 ± 6 ml(.) kg(-1.)min(-1)] undertook nine trials while wearing an EOD9 suit (weighing 33.4 kg). The trials involved walking on a treadmill at 2.5, 4 and 5.5 km ? h(-1) at each of the following environmental conditions, 21, 30 and 37 °C wet bulb globe temperature (WBGT) in a randomised controlled crossover design. The trials were ceased if the participants' core temperature reached 39 °C, if heart rate exceeded 90% of maximum, if walking time reached 60 minutes or due to fatigue/nausea. Tolerance times ranged from 10-60 minutes and were significantly reduced in the higher walking speeds and environmental conditions. In a total of 15 trials (21%) participants completed 60 minutes of walking; however, this was predominantly at the slower walking speeds in the 21 °C WBGT environment. Of the remaining 57 trials, 50 were ceased, due to attainment of 90% maximal heart rate. These near maximal heart rates resulted in moderate-high levels of physiological strain in all trials, despite core temperature only reaching 39 °C in one of the 72 trials.","author":[{"dropping-particle":"","family":"Stewart","given":"Ian B.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Stewart","given":"Kelly L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Worringham","given":"Charles J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Costello","given":"Joseph T.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"PLoS ONE","editor":[{"dropping-particle":"","family":"Hug","given":"Fran?ois","non-dropping-particle":"","parse-names":false,"suffix":""}],"id":"ITEM-1","issue":"2","issued":{"date-parts":[["2014","2","21"]]},"page":"e83740","title":"Physiological Tolerance Times while Wearing Explosive Ordnance Disposal Protective Clothing in Simulated Environmental Extremes","type":"article-journal","volume":"9"},"uris":["",""]}],"mendeley":{"formattedCitation":"<sup>108</sup>","plainTextFormattedCitation":"108","previouslyFormattedCitation":"<sup>108</sup>"},"properties":{"noteIndex":0},"schema":""}108,ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"URL":"","accessed":{"date-parts":[["2018","2","27"]]},"author":[{"dropping-particle":"","family":"Medtronic","given":"","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Medtronic - SmartPill WebPage","id":"ITEM-1","issued":{"date-parts":[["0"]]},"title":"SmartPill - Product Information","type":"webpage"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>228</sup>","plainTextFormattedCitation":"228","previouslyFormattedCitation":"<sup>229</sup>"},"properties":{"noteIndex":0},"schema":""}228, ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1208/s12249-014-0172-1","ISSN":"1530-9932","author":[{"dropping-particle":"","family":"Becker","given":"Dieter","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zhang","given":"Jin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Heimbach","given":"Tycho","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Penland","given":"Robert C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wanke","given":"Christoph","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shimizu","given":"Jeff","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kulmatycki","given":"Kenneth","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"AAPS PharmSciTech","id":"ITEM-1","issue":"6","issued":{"date-parts":[["2014","12","15"]]},"page":"1490-1497","title":"Novel Orally Swallowable IntelliCap? Device to Quantify Regional Drug Absorption in Human GI Tract Using Diltiazem as Model Drug","type":"article-journal","volume":"15"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>241</sup>","plainTextFormattedCitation":"241","previouslyFormattedCitation":"<sup>242</sup>"},"properties":{"noteIndex":0},"schema":""}241BiomarkersIn vivo human trials (Ovesco Hemopill)In vitro trials (all others)Stomach (Ovesco device)ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/TBME.2011.2158543","ISSN":"0018-9294","PMID":"21642037","abstract":"A characterization of gastrointestinal fluids has been performed by means of an electrochemical sensor that has potential for clinical in vivo and in vitro monitoring applications. The sensor comprised a three-electrode cell with a counter, reference, and four working electrodes, Au, Pt, Ir, and Rh. Cyclic voltammetry was used to obtain chemical information from faecal water (in vitro) and gut model (in vivo) fluids. Stable voltammetric responses were obtained for both fluids at these noble metal working electrodes. The responses differed in shape that demonstrated the discrimination capability and the potential for practical use as a tool for gastrointestinal fluid investigation. The analysis of the stability profiles in faecal water over a 14-h duration has indicated a possible adsorption mechanism with the formation of a biolayer on the sensor surface. The stability in gut model fluids over a 42-h duration has demonstrated a more stable profile, but the mechanisms involved are more complicated to determine.","author":[{"dropping-particle":"","family":"Twomey","given":"Karen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Alvarez de Eulate","given":"Eva","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Marchesi","given":"Julian R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kolida","given":"Sofia","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gibson","given":"Glenn","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Arrigan","given":"Damien W. 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This paper presents an alternative wireless device, with electrochemical sensing technique, which behaves autonomously as it travels through the GI tract. The capsule includes a direct access, multi electrode electronic tongue sensor that enables non-specific characterization of gut fluids, aiding in the diagnosis of gastrointestinal diseases such as Crohn's and ulcerative colitis. The sensor, interfaced through a potentiostatic circuit, is capable of performing various voltammetries such as cyclic, square wave and differential pulse techniques. A wireless communication link, operating at 433MHz, delivers measured data to a base station receiver located outside the body. The capsule, powered by a single lithium-ion cell and implemented on a polyimide flexible substrate, is encapsulated in polyether ether ketone (PEEK) material to measure 12mm in diameter and 28mm in length taking volume of approximately 4cm3. The capsule's front end potentiostat compares well with commercial laboratory equipment under the same cell and voltammetry conditions. The electrochemical characterization of the system and its application for electrochemical examination of faecal waters proves its potential as an in vivo GI tract diagnostic tool and other biomedical applications requiring a miniaturized low power sensing device.","author":[{"dropping-particle":"","family":"Caffrey","given":"C. Mc","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Twomey","given":"K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ogurtsov","given":"V.I.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Sensors and Actuators B: Chemical","id":"ITEM-2","issued":{"date-parts":[["2015","10"]]},"page":"8-15","publisher":"Elsevier B.V.","title":"Development of a wireless swallowable capsule with potentiostatic electrochemical sensor for gastrointestinal track investigation","type":"article-journal","volume":"218"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1109/JSEN.2016.2633435","ISSN":"1530-437X","author":[{"dropping-particle":"","family":"Yen","given":"Yi-Kuang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Capua","given":"Eyal","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Naaman","given":"Ron","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Sensors Journal","id":"ITEM-3","issue":"3","issued":{"date-parts":[["2017","2","1"]]},"page":"660-666","title":"Application of a GaAs-Based Sensor for Detecting Hemoglobin in Gastrointestinal Environments","type":"article-journal","volume":"17"},"uris":[""]},{"id":"ITEM-4","itemData":{"DOI":"10.1016/j.bios.2015.11.073","ISSN":"09565663","PMID":"26667093","abstract":"Acute upper gastrointestinal bleedings from ulcers or esophago-gastric varices are life threatening medical conditions which require immediate endoscopic therapy. Despite successful endoscopic hemostasis, there is a significant risk of rebleeding often requiring close surveillance of these patients in the intensive care unit (ICU). Any time delay to recognize bleeding may lead to a high blood loss and increases the risk of death. A novel telemetric real-time bleeding sensor can help indicate blood in the stomach: the sensor is swallowed to detect active bleeding or is anchored endoscopically on the gastrointestinal wall close to the potential bleeding source. By telemetric communication with an extra-corporeal receiver, information about the bleeding status is displayed. In this study the novel sensor, which measures characteristic optical properties of blood, has been evaluated in an ex-vivo setting to assess its clinical applicability and usability. Human venous blood of different concentrations, various fluids, and liquid food were tested. The LED-based sensor was able to reliably distinguish between concentrated blood and other liquids, especially red-colored fluids. In addition, the spectrometric quality of the small sensor (size: 6.5 mm in diameter, 25.5 mm in length) was comparable to a much larger and technically more complex laboratory spectrophotometer. The experimental data confirm the capability of a miniaturized sensor to identify concentrated blood, which could help in the very near future the detection of upper gastrointestinal bleeding and to survey high-risk patients for rebleeding.","author":[{"dropping-particle":"","family":"Schostek","given":"Sebastian","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zimmermann","given":"Melanie","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Keller","given":"Jan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fode","given":"Mario","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Melbert","given":"Michael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schurr","given":"Marc O.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gottwald","given":"Thomas","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Prosst","given":"Ruediger L.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Biosensors and Bioelectronics","id":"ITEM-4","issued":{"date-parts":[["2016","4"]]},"page":"524-529","publisher":"Elsevier","title":"Telemetric real-time sensor for the detection of acute upper gastrointestinal bleeding","type":"article-journal","volume":"78"},"uris":[""]},{"id":"ITEM-5","itemData":{"DOI":"10.1371/journal.pone.0166488","ISSN":"1932-6203","abstract":"There are no ideal means for the diagnosis of intestinal bleeding diseases as of now, particularly in the small intestine. This study investigated an intelligent intestinal bleeding detection capsule system based on color recognition. After the capsule is swallowed, the bleeding detection module (containing a color-sensitive adsorptive film that changes color when absorbing intestinal juice,) is used to identify intestinal bleeding features. A hue-saturation-light color space method can be applied to detect bleeding according to the range of H and S values of the film color. Once bleeding features are recognized, a wireless transmission module is activated immediately to send an alarm signal to the outside; an in vitro module receives the signal and sends an alarm. The average power consumption of the entire capsule system is estimated to be about 2.1mW. Owing to its simplicity, reliability, and effectiveness, this system represents a new approach to the clinical diagnosis of intestinal bleeding diseases.","author":[{"dropping-particle":"","family":"Qiao","given":"Panpan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Liu","given":"Hongying","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yan","given":"Xueping","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jia","given":"Ziru","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pi","given":"Xitian","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"PLOS ONE","editor":[{"dropping-particle":"","family":"Song","given":"Houbing","non-dropping-particle":"","parse-names":false,"suffix":""}],"id":"ITEM-5","issue":"11","issued":{"date-parts":[["2016","11","30"]]},"page":"e0166488","title":"A Smart Capsule System for Automated Detection of Intestinal Bleeding Using HSL Color Recognition","type":"article-journal","volume":"11"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>148–152</sup>","plainTextFormattedCitation":"148–152","previouslyFormattedCitation":"<sup>149–153</sup>"},"properties":{"noteIndex":0},"schema":""}148–152ElectrophysiologyEx vivo trialsSmall BowelADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1007/s11517-009-0567-4","ISSN":"0140-0118","PMID":"20039141","abstract":"A telemetry capsule system was designed and implemented to measure the slow wave activity of the small bowel, which is an important parameter for the diagnosis of gastric diseases. The capsule amplified the slow wave signal from the intraluminal electrodes, and transmitted the digitally sampled data by means of a radio frequency transmitter. The implemented capsule (11 x 21 mm(2)) was smaller than a commercially available capsule endoscope, and it can remain active for more than 18 h. The feasibility of using this capsule was investigated by conducting in vitro experiments, and the average motility signals of the ileum, jejunum, and colon were measured as 6.1, 10.2, and 1.5 cycles per minute, respectively","author":[{"dropping-particle":"","family":"Woo","given":"S H","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cho","given":"J H","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Medical & Biological Engineering & Computing","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2010","3","29"]]},"page":"277-283","title":"Telemetry system for slow wave measurement from the small bowel","type":"article-journal","volume":"48"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>127</sup>","plainTextFormattedCitation":"127","previouslyFormattedCitation":"<sup>128</sup>"},"properties":{"noteIndex":0},"schema":""}127Fluorescent imagingEx vivo trialsSmall Bowel (Demosthenous device)Stomach (Nemiroski device)ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1038/srep18591","ISSN":"2045-2322","PMID":"26678456","abstract":"Fluorescence Imaging (FI) is a powerful technique in biological science and clinical medicine. Current FI devices that are used either for in-vivo or in-vitro studies are expensive, bulky and consume substantial power, confining the technique to laboratories and hospital examination rooms. Here we present a miniaturised wireless fluorescence endoscope capsule with low power consumption that will pave the way for future FI systems and applications. With enhanced sensitivity compared to existing technology we have demonstrated that the capsule can be successfully used to image tissue autofluorescence and targeted fluorescence via fluorophore labelling of tissues. The capsule incorporates a state-of-the-art complementary metal oxide semiconductor single photon avalanche detector imaging array, miniaturised optical isolation, wireless technology and low power design. When in use the capsule consumes only 30.9 mW, and deploys very low-level 468 nm illumination. The device has the potential to replace highly power-hungry intrusive optical fibre based endoscopes and to extend the range of clinical examination below the duodenum. To demonstrate the performance of our capsule, we imaged fluorescence phantoms incorporating principal tissue fluorophores (flavins) and absorbers (haemoglobin). We also demonstrated the utility of marker identification by imaging a 20 μM fluorescein isothiocyanate (FITC) labelling solution on mammalian tissue.","author":[{"dropping-particle":"","family":"Al-Rawhani","given":"Mohammed A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Beeley","given":"James","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cumming","given":"David R. 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In this paper we present a cost-effective ( $500) screening capsule prototype, which is able to detect infrared (IR) fluorescence emitted by indocyanine green (ICG) fluorophore dye. Rather than image, the capsule works as a high-sensitivity fluorometer that records fluorescence levels throughout the small intestine. The presented mixed-signal system has a small size, consumes very little power ( ≈ 6.3 mA) and does not require an external belt and hardware for data collection. By determining fluorescence levels in the intestine, rather than collecting images, we avoid the need for labour intensive video analysis. The whole system is contained within a compact ingestible capsule, that is sized so as to come into close contact with the intestine walls during peristalsis. Ex-vivo experiments, on ICG-impregnated swine intestine, have shown that the prototype system is able to detect low concentrations of ICG in the nanomolar and micromolar region, which is required to detect early cancer in the small intestine.","author":[{"dropping-particle":"","family":"Demosthenous","given":"Panayiota","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pitris","given":"Constantinos","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Georgiou","given":"Julius","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Transactions on Biomedical Circuits and Systems","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2016","4"]]},"page":"467-476","title":"Infrared Fluorescence-Based Cancer Screening Capsule for the Small Intestine","type":"article-journal","volume":"10"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>82</sup>","plainTextFormattedCitation":"82","previouslyFormattedCitation":"<sup>82</sup>"},"properties":{"noteIndex":0},"schema":""}82 ,ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1039/C5LC00770D","ISBN":"1473-0197","ISSN":"1473-0197","PMID":"26490455","abstract":"A swallowable, capsular fluorometer simplifies detection of upper gastrointestinal bleeding by wirelessly detecting presence of fluorescein-spiked blood in the stomach.","author":[{"dropping-particle":"","family":"Nemiroski","given":"Alex","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ryou","given":"Marvin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Thompson","given":"Christopher C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Westervelt","given":"Robert M.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Lab on a Chip","id":"ITEM-1","issue":"23","issued":{"date-parts":[["2015"]]},"page":"4479-4487","title":"Swallowable fluorometric capsule for wireless triage of gastrointestinal bleeding","type":"article-journal","volume":"15"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>83</sup>","plainTextFormattedCitation":"83","previouslyFormattedCitation":"<sup>83</sup>"},"properties":{"noteIndex":0},"schema":""}83Gas sensingIn vivo, human trialsLarge IntestineADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1038/s41928-017-0004-x","ISBN":"2520-1131","ISSN":"2520-1131","abstract":"Ingestible sensors are potentially a powerful tool for monitoring human health. Sensors have been developed that can, for example, provide pH and pressure readings or monitor medication, but capsules that can provide key information about the chemical composition of the gut are still not available. Here we report a human pilot trial of an ingestible electronic capsule that can sense oxygen, hydrogen, and carbon dioxide. The capsule uses a combination of thermal conductivity and semiconducting sensors, and their selectivity and sensitivity to different gases is controlled by adjusting the heating elements of the sensors. Gas profiles of the subjects were obtained while modulating gut microbial fermentative activities by altering their intake of dietary fibre. Ultrasound imaging confirmed that the oxygen-equivalent concentration profile could be used as an accurate marker for the location of the capsule. In a crossover study, variations of fibre intake were found to be associated with differing small intestinal and colonic transit times, and gut fermentation. Regional fermentation patterns could be defined via hydrogen gas profiles. Our gas capsule offers an accurate and safe tool for monitoring the effects of diet of individuals, and has the potential to be used as a diagnostic tool for the gut.","author":[{"dropping-particle":"","family":"Kalantar-Zadeh","given":"Kourosh","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Berean","given":"Kyle J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ha","given":"Nam","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chrimes","given":"Adam F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Xu","given":"Kai","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Grando","given":"Danilla","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ou","given":"Jian Zhen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pillai","given":"Naresh","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Campbell","given":"Jos L.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Brklja?a","given":"Robert","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Taylor","given":"Kirstin M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Burgell","given":"Rebecca E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yao","given":"Chu K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ward","given":"Stephanie A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"McSweeney","given":"Chris S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Muir","given":"Jane G.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gibson","given":"Peter R.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Nature Electronics","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2018"]]},"page":"79-87","publisher":"Springer US","title":"A human pilot trial of ingestible electronic capsules capable of sensing different gases in the gut","type":"article-journal","volume":"1"},"uris":[""]},{"id":"ITEM-2","itemData":{"DOI":"10.1053/j.gastro.2015.07.072","ISSN":"00165085","author":[{"dropping-particle":"","family":"Kalantar-zadeh","given":"Kourosh","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yao","given":"Chu K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Berean","given":"Kyle J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ha","given":"Nam","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ou","given":"Jian Zhen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ward","given":"Stephanie A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pillai","given":"Naresh","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hill","given":"Julian","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cottrell","given":"Jeremy J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dunshea","given":"Frank R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"McSweeney","given":"Chris","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Muir","given":"Jane G.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gibson","given":"Peter R.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Gastroenterology","id":"ITEM-2","issue":"1","issued":{"date-parts":[["2016","1"]]},"page":"37-39","title":"Intestinal Gas Capsules: A Proof-of-Concept Demonstration","type":"article-journal","volume":"150"},"uris":[""]},{"id":"ITEM-3","itemData":{"DOI":"10.1038/srep33387","ISSN":"20452322","abstract":"? 2016 The Author(s). Gastroenterologists are still unable to differentiate between some of the most ordinary disorders of the gut and consequently patients are misdiagnosed. We have developed a swallowable gas sensor capsule for addressing this. The gases of the gut are the by-product of the fermentation processes during digestion, affected by the gut state and can consequently provide the needed information regarding the health of the gut. Here we present the first study on gas sensor capsules for revealing the effect of a medical supplement in an animal (pig) model. We characterise the real-time alterations of gastric-gas in response to environmental heat-stress and dietary cinnamon and use the gas profiles for understanding the bio-physiological changes. Under no heat-stress, feeding increases gastric CO 2 concentration, while dietary cinnamon reduces it due to decrease in gastric acid and pepsin secretion. Alternatively, heat-stress leads to hyperventilation in pigs, which reduces CO 2 concentration and with the cinnamon treatment, CO 2 diminishes even more, resulting in health improvement outcomes. Overall, a good repeatability in gas profiles is also observed. The model demonstrates the strong potential of real-time gas profiler in providing new physiological information that will impact understanding of therapeutics, presenting a highly reliable device for monitoring/diagnostics of gastrointestinal disorders.","author":[{"dropping-particle":"","family":"Ou","given":"Jian Zhen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cottrell","given":"Jeremy J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ha","given":"Nam","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pillai","given":"Naresh","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yao","given":"Chu K.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Berean","given":"Kyle J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ward","given":"Stephanie A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Grando","given":"Danilla","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Muir","given":"Jane G.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Harrison","given":"Christopher J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wijesiriwardana","given":"Udani","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Dunshea","given":"Frank R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gibson","given":"Peter R.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kalantar-Zadeh","given":"Kourosh","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Scientific Reports","id":"ITEM-3","issue":"September","issued":{"date-parts":[["2016"]]},"page":"1-9","publisher":"Nature Publishing Group","title":"Potential of in vivo real-time gastric gas profiling: A pilot evaluation of heat-stress and modulating dietary cinnamon effect in an animal model","type":"article-journal","volume":"6"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>158–160</sup>","plainTextFormattedCitation":"158–160","previouslyFormattedCitation":"<sup>159–161</sup>"},"properties":{"noteIndex":0},"schema":""}158–160Ionizing radiationIn vivo, human trialsLarge IntestineADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1007/s00261-016-1026-y","ISBN":"0026101610","ISSN":"2366-004X","abstract":"? 2017, Springer Science+Business Media New York. Many patients are reluctant to undergo optical colonoscopy for colorectal cancer screening. The Check-Cap colon imaging system is a non-invasive test that comprises an ingestible imaging capsule that emits and detects ultra-low-dose radiation. The capsule generates a 3D reconstruction of the colonic lumen for detection of polyps and cancer. Preliminary preclinical and clinical testing has demonstrated safety and feasibility. Mean radiation dose is estimated at 0.04 mSv. In conclusion, we describe a novel capsule-based, patient-friendly colorectal test that holds potential for non-invasive screening.","author":[{"dropping-particle":"","family":"Kimchy","given":"Yoav","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lifshitz","given":"Ronen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lewkowitz","given":"Shlomo","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bertuccio","given":"Guiseppe","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Arber","given":"Nadir","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gluck","given":"Nathan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Pickhardt","given":"Perry J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Abdominal Radiology","id":"ITEM-1","issue":"5","issued":{"date-parts":[["2017","5","4"]]},"page":"1291-1297","title":"Radiographic capsule-based system for non-cathartic colorectal cancer screening","type":"article-journal","volume":"42"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>103</sup>","plainTextFormattedCitation":"103","previouslyFormattedCitation":"<sup>103</sup>"},"properties":{"noteIndex":0},"schema":""}103,ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1117/12.2254242","ISBN":"978-1-5106-0709-5; 978-1-5106-0710-1","ISSN":"0277-786X","abstract":"An ingestible capsule for colorectal cancer screening, based on ionizing-radiation imaging, has been developed and is in advanced stages of system stabilization and clinical evaluation. The imaging principle allows future patients using this technology to avoid bowel cleansing, and to continue the normal life routine during procedure. The Check-Cap capsule, or C-Scan (R) Cap, imaging principle is essentially based on reconstructing scattered radiation, while both radiation source and radiation detectors reside within the capsule. The radiation source is a custom-made radioisotope encased in a small canister, collimated into rotating beams. While traveling along the human colon, irradiation occurs from within the capsule towards the colon wall. Scattering of radiation occurs both inside and outside the colon segment; some of this radiation is scattered back and detected by sensors onboard the capsule. During procedure, the patient receives small amounts of contrast agent as an addition to his/her normal diet. The presence of contrast agent inside the colon dictates the dominant physical processes to become Compton Scattering and X-Ray Fluorescence (XRF), which differ mainly by the energy of scattered photons. The detector readout electronics incorporates low-noise Single Photon Counting channels, allowing separation between the products of these different physical processes. Separating between radiation energies essentially allows estimation of the distance from the capsule to the colon wall, hence structural imaging of the intraluminal surface. 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A novel prepless X-ray imaging capsule for colon screening is presented; the capsule emits low dose X-rays, which are scattered by ingested contrast agent mixed with colon contents, and sensed by detectors in the capsule to generate high-resolution three-dimensional (3D) imagery of the colon without bowel cleansing. Following preliminary studies with implanted polyps in synthetic colon phantoms, bovine cadaver and live swine, and human experi-ments with dummy capsules (n=75), 49 patients swallowed the capsule with natural excretion in 48 after 73.2±45.4 h. Pedunculated and sessile polyps were clearly seen and validated by subsequent col-onoscopy. Total radiation exposure was ultra low (0.03±0.007 mSv). 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Results in human subjects show that this technique rapidly provides three-dimensional, microstructural images of the upper gastrointestinal tract in a simple and painless procedure, opening up new opportunities for screening for internal diseases.","author":[{"dropping-particle":"","family":"Gora","given":"Michalina J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sauk","given":"Jenny S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Carruth","given":"Robert W.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gallagher","given":"Kevin A.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Suter","given":"Melissa J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Nishioka","given":"Norman S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kava","given":"Lauren E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rosenberg","given":"Mireille","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bouma","given":"Brett E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tearney","given":"Guillermo J.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Nature Medicine","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2013","2","13"]]},"page":"238-240","title":"Tethered capsule endomicroscopy enables less invasive imaging of gastrointestinal tract microstructure","type":"article-journal","volume":"19"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>98</sup>","plainTextFormattedCitation":"98","previouslyFormattedCitation":"<sup>98</sup>"},"properties":{"noteIndex":0},"schema":""}98, ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1364/BOE.6.001146","ISBN":"2156-7085","ISSN":"2156-7085","PMID":"25909001","abstract":"Depth resolved and en face OCT visualization in vivo may have important clinical applications in endoscopy. We demonstrate a high speed, two-dimensional (2D) distal scanning capsule with a micromotor for fast rotary scanning and a pneumatic actuator for precision longitudinal scanning. Longitudinal position measurement and image registration were performed by optical tracking of the pneumatic scanner. The 2D scanning device enables high resolution imaging over a small field of view and is suitable for OCT as well as other scanning microscopies. Large field of view imaging for screening or surveillance applications can also be achieved by proximally pulling back or advancing the capsule while scanning the distal high-speed micromotor. Circumferential en face OCT was demonstrated in living swine at 250 Hz frame rate and 1 MHz A-scan rate using a MEMS tunable VCSEL light source at 1300 nm. Cross-sectional and en face OCT views of the upper and lower gastrointestinal tract were generated with precision distal pneumatic longitudinal actuation as well as proximal manual longitudinal actuation. These devices could enable clinical studies either as an adjunct to endoscopy, attached to an endoscope, or as a swallowed tethered capsule for non-endoscopic imaging without sedation. The combination of ultrahigh speed imaging and distal scanning capsule technology could enable both screening and surveillance applications.","author":[{"dropping-particle":"","family":"Liang","given":"Kaicheng","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Traverso","given":"Giovanni","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lee","given":"Hsiang-Chieh","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ahsen","given":"Osman Oguz","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wang","given":"Zhao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Potsaid","given":"Benjamin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Giacomelli","given":"Michael","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Jayaraman","given":"Vijaysekhar","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Barman","given":"Ross","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cable","given":"Alex","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mashimo","given":"Hiroshi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Langer","given":"Robert","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fujimoto","given":"James G.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Biomedical Optics Express","id":"ITEM-1","issue":"4","issued":{"date-parts":[["2015","4","1"]]},"page":"1146","title":"Ultrahigh speed en face OCT capsule for endoscopic imaging","type":"article-journal","volume":"6"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>99</sup>","plainTextFormattedCitation":"99","previouslyFormattedCitation":"<sup>99</sup>"},"properties":{"noteIndex":0},"schema":""}99Ultrasonography In vivo, animal trialsSmall Bowel (Sonopill device)Entire tract (Stanford device)ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/ULTSYM.2016.7728851","ISBN":"978-1-4673-9897-8","abstract":"We are developing a capsule ultrasound (CUS) device - a pill with the capability to scan the gastrointestinal (GI) tract through ultrasound. In this paper, we discuss the design and fabrication of the main components of the CUS device including the CMUT array, front-end electronics, and the wireless transmitter. We demonstrate a successfully fabricated 128-element CMUT array with polydimethylsiloxane (PDMS)-filled trenches and show their input impedance in air. The front-end electronics, measuring 6 mm by 6 mm and the high-data rate wireless transmitter, measuring 1 mm by 1.76 mm, have been fabricated. Our preliminary power analysis indicates that our total power consumption is less than 20 mW for the CUS device. 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Although WCE provides high quality images of the GI tract, evaluation is limited to the mucosal surface. This work investigates feasibility and design considerations for wireless capsule endoscopic ultrasound (WCEU) that combines the benefits of WCE and ultrasound imaging. This work has two goals: (1) evaluate transducer designs appropriate for WCEU and (2) investigate whether peristalsis can produce sufficient contact to ensure acoustic coupling. Between mechanical scanning (MS) and side-looking array (SLA) designs, MS performs better for both imaging performance and system complexity. In vivo imaging in pigs demonstrates promising results, although the effect of peristalsis and resulting coverage needs further investigation and quantification.","author":[{"dropping-particle":"","family":"Lee","given":"John H.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Traverso","given":"Giovanni","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Schoellhammer","given":"Carl M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Blankschtein","given":"Daniel","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Langer","given":"Robert","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Thomenius","given":"Kai E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Boning","given":"Duane S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Anthony","given":"Brian W.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"2014 IEEE International Ultrasonics Symposium","id":"ITEM-1","issued":{"date-parts":[["2014","9"]]},"page":"734-737","publisher":"IEEE","title":"Towards wireless capsule endoscopic ultrasound (WCEU)","title-short":"Ultrasonics Symposium (IUS), 2014 IEEE Internation","type":"paper-conference"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>64</sup>","plainTextFormattedCitation":"64","previouslyFormattedCitation":"<sup>64</sup>"},"properties":{"noteIndex":0},"schema":""}64 NBI, narrow band imagingTable SEQ Table \* ARABIC 4: Accuracy, sensitivity and specificity of in vivo, computer aided diagnosis for human gastrointestinal pathologies using capsule endoscopy PathologyTotal number of images in datasetNumber of images in dataset with pathologySensitivitySpecificityAccuracyYearReferenceBleeding5000100099.00%94.00%95.00%2014ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/JBHI.2013.2257819","ISBN":"2168-2194 VO - 18","ISSN":"21682194","PMID":"24608063","abstract":"Wireless capsule endoscopy (WCE) can directly take digital images in the gastrointestinal tract of a patient. It has opened a new chapter in small intestine examination. However, a major problem associated with this technology is that too many images need to be manually examined by clinicians. Currently, there is no standard for capsule endoscopy image interpretation and classification. Most state-of-the-art CAD methods often suffer from poor performance, high computational cost, or multiple empirical thresholds. In this paper, a new method for rapid bleeding detection in the WCE video is proposed. We group pixels through superpixel segmentation to reduce the computational complexity while maintaining high diagnostic accuracy. Feature of each superpixel is extracted using the red ratio in RGB space and fed into support vector machine for classification. Also, the influence of edge pixels has been removed in this paper. Comparative experiments show that our algorithm is superior to the existing methods in terms of sensitivity, specificity, and accuracy.","author":[{"dropping-particle":"","family":"Fu","given":"Yanan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zhang","given":"Wei","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mandal","given":"Mrinal","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Meng","given":"Max Q H","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Journal of Biomedical and Health Informatics","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2014"]]},"page":"636-642","title":"Computer-aided bleeding detection in WCE video","type":"article-journal","volume":"18"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>213</sup>","plainTextFormattedCitation":"213","previouslyFormattedCitation":"<sup>214</sup>"},"properties":{"noteIndex":0},"schema":""}21360722093.84%NR92.86%2014ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.4236/jsea.2014.75039","ISSN":"1945-3116","abstract":"Wireless capsule endoscopes (WCEs) have been used widely to detect abnormalities inside regions of the small intestine that are not accessible when using traditional endoscopy techniques. However, an experienced clinician must spend an average of 2 hours to view and analyze the approximately 60,000 images produced during one examination. Therefore, developing a computer-aided system for processing WCE images is crucial. This paper proposes a novel method used for detecting bleeding and ulcers in WCE images. This approach involves using color features to determine the status of the small intestine. The experimental results revealed that the proposed scheme is promising in detecting bleeding and ulcer regions.","author":[{"dropping-particle":"","family":"Yeh","given":"Jinn-Yi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wu","given":"Tai-Hsi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tsai","given":"Wei-Jun","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Software Engineering and Applications","id":"ITEM-1","issue":"05","issued":{"date-parts":[["2014"]]},"page":"422-432","title":"Bleeding and Ulcer Detection Using Wireless Capsule Endoscopy Images","type":"article-journal","volume":"07"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>214</sup>","plainTextFormattedCitation":"214","previouslyFormattedCitation":"<sup>215</sup>"},"properties":{"noteIndex":0},"schema":""}2141004582.30%89.10%NR2012ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"ISBN":"9781457721779","author":[{"dropping-particle":"","family":"Xiaoying Liu, lia Gu, Yaoqin Xie","given":"lun Xiong and Wenjian Qin","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE-EMBS International Conference on Biomedical and Health Informatics","id":"ITEM-1","issue":"Bhi","issued":{"date-parts":[["2012"]]},"page":"737-740","title":"A New Approach to Detecting Ulcer and Bleeding in Wireless Capsule Endoscopy Images","type":"article-journal","volume":"25"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>215</sup>","plainTextFormattedCitation":"215","previouslyFormattedCitation":"<sup>216</sup>"},"properties":{"noteIndex":0},"schema":""}2151005080.00%95.30%94.40%2014ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1007/s10916-014-0025-1","ISBN":"1091601400251","ISSN":"1573689X","PMID":"24696394","abstract":"Wireless Capsule Endoscopy (WCE) is a technology in the field of endoscopic imaging which facilitates direct visualization of the entire small intestine. Many algorithms are being developed to automatically identify clinically important frames in WCE videos. This paper presents a supervised method for automated detection of bleeding regions present in WCE frames or images. The proposed method characterizes the image regions by using statistical features derived from the first order histogram probability of the three planes of RGB color space. Despite being inconsistent and tiresome, manual selection of regions has been a popular technique for creating training data in the studies of capsule endoscopic images. We propose a semi-automatic region-annotation algorithm for creating training data efficiently. All possible combinations of different features are exhaustively analyzed to find the optimum feature set with the best performance. During operation, regions from images are obtained by applying a segmentation method. Finally, a trained neural network recognizes the patterns of the data arising from bleeding and non-bleeding regions.","author":[{"dropping-particle":"","family":"Sainju","given":"Sonu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bui","given":"Francis M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wahid","given":"Khan A.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Medical Systems","id":"ITEM-1","issue":"4","issued":{"date-parts":[["2014"]]},"title":"Automated bleeding detection in capsule endoscopy videos using statistical features and region growing","type":"article-journal","volume":"38"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>198</sup>","plainTextFormattedCitation":"198","previouslyFormattedCitation":"<sup>199</sup>"},"properties":{"noteIndex":0},"schema":""}198240040092.00%96.50%95.75%2016ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/JBHI.2015.2399502","ISBN":"9781479969234","ISSN":"21682194","PMID":"25675468","abstract":"Wireless capsule endoscopy (WCE) enables non-invasive and painless direct visual inspection of a patient's whole digestive tract, but at the price of long time reviewing large amount of images by clinicians. Thus an automatic computer-aided technique to reduce the burden of physicians is highly demanded. In this paper, we propose a novel color feature extraction method to discriminate the bleeding frames from the normal ones, with further localization of the bleeding regions. Our proposal is based on a twofold system. First, we make full use of the color information of WCE images and utilize K-means clustering method on the pixel represented images to obtain the cluster centers, with which we characterize WCE images as words based color histograms. Then we judge the status of a WCE frame by applying support vector machine (SVM) and K nearest neighbor (KNN) methods. Comprehensive experimental results reveal that the best classification performance is obtained with YCbCr color space, cluster number 80 and the SVM. The achieved classification performance reaches 95.75% in accuracy, 0.9771 for AUC, validating that the proposed scheme provides an exciting performance for bleeding classification. Secondly, we propose a two-stage saliency map extraction method to highlight bleeding regions where the first stage saliency map is created by means of different color channels mixer and the second stage saliency map is obtained from the visual contrast. Followed by an appropriate fusion strategy and threshold, we localize the bleeding areas. Quantitative as well as qualitative results show that our methods could differentiate the bleeding areas from neighborhoods correctly.","author":[{"dropping-particle":"","family":"Yuan","given":"Yixuan","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Li","given":"Baopu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Meng","given":"Max Q.H.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Journal of Biomedical and Health Informatics","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2016"]]},"page":"624-630","title":"Bleeding Frame and Region Detection in the Wireless Capsule Endoscopy Video","type":"article-journal","volume":"20"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>216</sup>","plainTextFormattedCitation":"216","previouslyFormattedCitation":"<sup>217</sup>"},"properties":{"noteIndex":0},"schema":""}216120060099.41%98.95%99.19%2015ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.cmpb.2015.09.005","ISSN":"18727565","PMID":"26390947","abstract":"Background and objective: Wireless Capsule Endoscopy (WCE) can image the portions of the human gastrointestinal tract that were previously unreachable for conventional endoscopy examinations. A major drawback of this technology is that a large volume of data are to be analyzed in order to detect a disease which can be time-consuming and burdensome for the clinicians. Consequently, there is a dire need of computer-aided disease detection schemes to assist the clinicians. In this paper, we propose a real-time, computationally efficient and effective computerized bleeding detection technique applicable for WCE technology. Methods: The development of our proposed technique is based on the observation that characteristic patterns appear in the frequency spectrum of the WCE frames due to the presence of bleeding region. Discovering these discriminating patterns, we develop a texture-feature-descriptor-based-algorithm that operates on the Normalized Gray Level Co-occurrence Matrix (NGLCM) of the magnitude spectrum of the images. A new local texture descriptor called difference average that operates on NGLCM is also proposed. We also perform statistical validation of the proposed scheme. Results: The proposed algorithm was evaluated using a publicly available WCE database. The training set consisted of 600 bleeding and 600 non-bleeding frames. This set was used to train the SVM classifier. On the other hand, 860 bleeding and 860 non-bleeding images were selected from the rest of the extracted images to form the test set. The accuracy, sensitivity and specificity obtained from our method are 99.19%, 99.41% and 98.95% respectively which are significantly higher than state-of-the-art methods. In addition, the low computational cost of our method makes it suitable for real-time implementation. Conclusion: This work proposes a bleeding detection algorithm that employs textural features from the magnitude spectrum of the WCE images. Experimental outcomes backed by statistical validations prove that the proposed algorithm is superior to the existing ones in terms of accuracy, sensitivity, specificity and computational cost.","author":[{"dropping-particle":"","family":"Hassan","given":"Ahnaf Rashik","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Haque","given":"Mohammad Ariful","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Computer Methods and Programs in Biomedicine","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2015"]]},"page":"341-353","publisher":"Elsevier Ireland Ltd","title":"Computer-aided gastrointestinal hemorrhage detection in wireless capsule endoscopy videos","type":"article-journal","volume":"122"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>197</sup>","plainTextFormattedCitation":"197","previouslyFormattedCitation":"<sup>198</sup>"},"properties":{"noteIndex":0},"schema":""}1977648193392.32%95.07%94.50%2018ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.bspc.2017.10.011","ISSN":"17468108","abstract":"Capsule Endoscopy (CE) is a non-invasive clinical procedure that allows examination of the entire gastrointestinal tract including parts of small intestine beyond the scope of conventional endoscope. It requires computer-aided approach for the assessment of video frames to reduce diagnosis time. This paper presents a computer-assisted method based on a classifier fusion algorithm which combines two optimized Support Vector Machine (SVM) classifiers to automatically detect bleeding regions present in CE frames. The classifiers are based on RGB and HSV color spaces; the image regions are characterized on the basis of statistical features derived from the first-order histogram probability of respective color channels. A nested cross validation strategy has been adopted for the parameter tuning and feature selection to optimize the classifiers. The optimum feature sets for the best performance are evaluated after exhaustive analysis. The proposed fusion approach achieves an average accuracy of 95%, sensitivity of 94% and specificity of 95.3% for a dataset of 8872 CE frames, which is higher than that obtained from a single classifier. Comparison with the state-of-the-art algorithms exhibits that the proposed method yields superior performance for diverse dataset.","author":[{"dropping-particle":"","family":"Deeba","given":"Farah","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Islam","given":"Monzurul","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Bui","given":"Francis M.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wahid","given":"Khan A.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Biomedical Signal Processing and Control","id":"ITEM-1","issued":{"date-parts":[["2018"]]},"page":"415-424","publisher":"Elsevier Ltd","title":"Performance assessment of a bleeding detection algorithm for endoscopic video based on classifier fusion method and exhaustive feature selection","type":"article-journal","volume":"40"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>196</sup>","plainTextFormattedCitation":"196","previouslyFormattedCitation":"<sup>197</sup>"},"properties":{"noteIndex":0},"schema":""}196Inflammatory and Vascular Lesions1377795.01%83.02%89.01%2014ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/ICIP.2014.7025453","ISBN":"9781479957514","author":[{"dropping-particle":"","family":"Iakovidis","given":"Dimitris K","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Koulaouzidis","given":"Anastasios","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Image Processing (ICIP), 2014 IEEE International Conference on. IEEE","id":"ITEM-1","issued":{"date-parts":[["2014"]]},"page":"2236-2240","title":"Automatic lesion detection in wireless capsule endoscopy - A simple solution for a complex problem","type":"article-journal"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>202</sup>","plainTextFormattedCitation":"202","previouslyFormattedCitation":"<sup>203</sup>"},"properties":{"noteIndex":0},"schema":""}202Common lesions and Angioectasia52374415678.6 – 9.4%92.1%-30.5%91.3%-35.7%2008ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.3748/wjg.14.6929","ISBN":"8628854223","ISSN":"10079327","PMID":"19058327","abstract":"AIM: To investigate and evaluate the feasibility of the computer-aided screening diagnosis for enteric lesions in the capsule endoscopy (CE). METHODS: After developing a series of algorithms for the screening diagnosis of the enteric lesions in CE based on their characteristic colors and contours, the normal and abnormal images obtained from 289 patients were respectively scanned and diagnosed by the CE readers and by the computer-aided screening for the enteric lesions with the image-processed software (IPS). The enteric lesions shown by the images included esoenteritis, mucosal ulcer and erosion, bleeding, space-occupying lesions, angioectasia, diverticula, parasites, etc. The images for the lesions or the suspected lesions confirmed by the CE readers and the computers were collected, and the effectiveness rate of the screening and the number of the scanned images were evaluated, respectively. RESULTS: Compared with the diagnostic results obtained by the CE readers, the total effectiveness rate (sensitivity) in the screening of the commonly-encountered enteric lesions by IPS varied from 42.9% to 91.2%, with a median of 74.2%, though the specificity and the accuracy rates were still low, and the images for the rarely-encountered lesions were difficult to differentiate from the normal images. However, the number of the images screened by IPS was 5000 on average, and only 10%-15% of the original images were left behind. As a result, a large number of normal images were excluded, and the reading time decreased from 5 h to 1 h on average. CONCLUSION: Though the total accuracy and specificity rates by the computer-aided screening for the enteric lesions with IPS are much lower than those by the CE readers, the computer-aided screening diagnosis can exclude a large number of the normal images and confine the enteric lesions to 5000 images on average, which can reduce the workload of the readers in the scanning of the images. This computer-aided screening technique can make a correct diagnosis as efficiently as possible in most of the patients.","author":[{"dropping-particle":"","family":"Gan","given":"Tao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wu","given":"Jun Chao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Rao","given":"Ni Ni","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chen","given":"Tao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Liu","given":"Bing","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"World Journal of Gastroenterology","id":"ITEM-1","issue":"45","issued":{"date-parts":[["2008"]]},"page":"6929-6935","title":"A feasibility trial of computer-aided diagnosis for enteric lesions in capsule endoscopy","type":"article-journal","volume":"14"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>203</sup>","plainTextFormattedCitation":"203","previouslyFormattedCitation":"<sup>204</sup>"},"properties":{"noteIndex":0},"schema":""}203Polyps1896823047.4%90.2%NR2013ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"author":[{"dropping-particle":"V","family":"Mamonov","given":"Alexander","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Figueiredo","given":"Isabel N","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Figueiredo","given":"Pedro N","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tsai","given":"Yen-hsi Richard","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Ices Report 13-10","id":"ITEM-1","issue":"7","issued":{"date-parts":[["2013"]]},"page":"1-16","title":"Automated polyp detection in colon capsule endoscopy by Automated polyp detection in colon capsule endoscopy","type":"article-journal","volume":"33"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>212</sup>","plainTextFormattedCitation":"212","previouslyFormattedCitation":"<sup>213</sup>"},"properties":{"noteIndex":0},"schema":""}212Ulcers1608082.50%100%91.25%2009ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/ROBIO.2009.5420455","ISBN":"9781424447756","author":[{"dropping-particle":"","family":"Li","given":"Baopu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Qi","given":"Lin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Meng","given":"Max Q","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ieee","given":"Fellow","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Fan","given":"Yichen","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Member","given":"Student","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE International Conference on Robotics and Biomimetics","id":"ITEM-1","issued":{"date-parts":[["2009"]]},"page":"2326-2331","title":"Using ensemble classifier for small bowel ulcer detection in wireless capsule endoscopy images","type":"article-journal"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>204</sup>","plainTextFormattedCitation":"204","previouslyFormattedCitation":"<sup>205</sup>"},"properties":{"noteIndex":0},"schema":""}20426013084.51%88.56%86.54%2013ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/CBMS.2013.6627801","ISBN":"9781479910533","ISSN":"10637125","author":[{"dropping-particle":"","family":"Eid","given":"Alexis","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Charisis","given":"Vasileios S.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Hadjileontiadis","given":"Leontios J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Sergiadis","given":"George D.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Proceedings of CBMS 2013 - 26th IEEE International Symposium on Computer-Based Medical Systems","id":"ITEM-1","issued":{"date-parts":[["2013"]]},"page":"273-278","title":"A curvelet-based lacunarity approach for ulcer detection from Wireless Capsule Endoscopy images","type":"article-journal"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>205</sup>","plainTextFormattedCitation":"205","previouslyFormattedCitation":"<sup>206</sup>"},"properties":{"noteIndex":0},"schema":""}2051376596.62%91.67%94.16%2015ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/ECS.2015.7124881","ISBN":"9781479972241","abstract":"? 2015 IEEE. The entire visualization of GastroIntestinal (GI) tract is not possible with conventional endoscopic exams. Wireless Capsule Endoscopy (WCE) is a low risk, painless, noninvasive procedure for diagnosing diseases such as bleeding, polyps, ulcers, and Crohns disease within the human digestive tract, especially the small intestine that was unreachable using the traditional endoscopic methods. However, analysis of massive images of WCE detection is tedious and time consuming to physicians. Hence, researchers have developed software methods to detect these diseases automatically. Thus, the effectiveness of WCE can be improved. In this paper, a novel textural feature extraction method is proposed based on Contourlet transform and Log Gabor filter to distinguish ulcer regions from normal regions. The results show that the proposed method performs well with a high accuracy rate of 94.16% using Support Vector Machine (SVM) classifier in HSV colour space.","author":[{"dropping-particle":"","family":"Koshy","given":"Nimisha Elsa","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gopi","given":"Varun P.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"2nd International Conference on Electronics and Communication Systems, ICECS 2015","id":"ITEM-1","issued":{"date-parts":[["2015"]]},"page":"1725-1729","title":"A new method for ulcer detection in endoscopic images","type":"paper-conference"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>206</sup>","plainTextFormattedCitation":"206","previouslyFormattedCitation":"<sup>207</sup>"},"properties":{"noteIndex":0},"schema":""}206Tumour1206088.60%96.20%92.40%2012ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/TITB.2012.2185807","ISBN":"1089-7771","ISSN":"10897771","PMID":"22287246","abstract":"Tumor in digestive tract is a common disease and wireless capsule endoscopy (WCE) is a relatively new technology to examine diseases for digestive tract especially for small intestine. This paper addresses the problem of automatic recognition of tumor for WCE images. Candidate color texture feature that integrates uniform local binary pattern and wavelet is proposed to characterize WCE images. The proposed features are invariant to illumination change and describe multiresolution characteristics of WCE images. Two feature selection approaches based on support vector machine, sequential forward floating selection and recursive feature elimination, are further employed to refine the proposed features for improving the detection accuracy. Extensive experiments validate that the proposed computer-aided diagnosis system achieves a promising tumor recognition accuracy of 92.4% in WCE images on our collected data.","author":[{"dropping-particle":"","family":"Li","given":"Baopu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Meng","given":"Max Q H","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Transactions on Information Technology in Biomedicine","id":"ITEM-1","issue":"3","issued":{"date-parts":[["2012"]]},"page":"323-329","title":"Tumor recognition in wireless capsule endoscopy images using textural features and SVM-based feature selection","type":"article-journal","volume":"16"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>207</sup>","plainTextFormattedCitation":"207","previouslyFormattedCitation":"<sup>208</sup>"},"properties":{"noteIndex":0},"schema":""}207120060092.33%88.67%90.50%2011ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/j.artmed.2011.01.003","ISBN":"0933-3657","ISSN":"09333657","PMID":"21353503","abstract":"Objective: Capsule endoscopy is useful in the diagnosis of small bowel diseases. However, the large number of images produced in each test is a tedious task for physicians. To relieve burden of physicians, a new computer-aided detection scheme is developed in this study, which aims to detect small bowel tumors for capsule endoscopy. Methods and materials: A novel textural feature based on multi-scale local binary pattern is proposed to discriminate tumor images from normal images. Since tumor in small bowel exhibit great diversities in appearance, multiple classifiers are employed to improve detection accuracy. 1200 capsule endoscopy images chosen from 10 patients' data constitute test data in our experiment. Results: Multiple classifiers based on k-nearest neighbor, multilayer perceptron neural network and support vector machine, which are built from six different ensemble rules, are experimented in three different color spaces. The results demonstrate an encouraging detection accuracy of 90.50%, together with a sensitivity of 92.33% and a specificity of 88.67%. Conclusion: The proposed scheme using color texture features and classifier ensemble is promising for small bowel tumor detection in capsule endoscopy images. ? 2011 Elsevier B.V.","author":[{"dropping-particle":"","family":"Li","given":"Baopu","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Meng","given":"Max Q.H.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lau","given":"James Y.W.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Artificial Intelligence in Medicine","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2011"]]},"page":"11-16","publisher":"Elsevier B.V.","title":"Computer-aided small bowel tumor detection for capsule endoscopy","type":"article-journal","volume":"52"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>211</sup>","plainTextFormattedCitation":"211","previouslyFormattedCitation":"<sup>212</sup>"},"properties":{"noteIndex":0},"schema":""}211180090097.80%96.70%97.30%2016ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1016/pbiomed.2016.01.021","ISBN":"0010-4825","ISSN":"18790534","PMID":"26829705","abstract":"Wireless capsule endoscopy (WCE) has been a revolutionary technique to noninvasively inspect gastrointestinal (GI) tract diseases, especially small bowel tumor. However, it is a tedious task for physicians to examine captured images. To develop a computer-aid diagnosis tool for relieving the huge burden of physicians, the intestinal video data from 89 clinical patients with the indications of potential tumors was analyzed. Out of the 89 patients, 15(16.8%) were diagnosed with small bowel tumor. A novel set of textural features that integrate multi-scale curvelet and fractal technology were proposed to distinguish normal images from tumor images. The second order textural descriptors as well as higher order moments between different color channels were computed from images synthesized by the inverse curvelet transform of the selected scales. Then, a classification approach based on support vector machine (SVM) and genetic algorithm (GA) was further employed to select the optimal feature set and classify the real small bowel images. Extensive comparison experiments validate that the proposed automatic diagnosis scheme achieves a promising tumor classification performance of 97.8% sensitivity and 96.7% specificity in the selected images from our clinical data.","author":[{"dropping-particle":"","family":"Liu","given":"Gang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yan","given":"Guozheng","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Kuang","given":"Shuai","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wang","given":"Yongbing","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Computers in Biology and Medicine","id":"ITEM-1","issued":{"date-parts":[["2016"]]},"page":"131-138","publisher":"Elsevier","title":"Detection of small bowel tumor based on multi-scale curvelet analysis and fractal technology in capsule endoscopy","type":"article-journal","volume":"70"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>208</sup>","plainTextFormattedCitation":"208","previouslyFormattedCitation":"<sup>209</sup>"},"properties":{"noteIndex":0},"schema":""}208300070093.90%93.10%NR2012ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1186/1475-925X-11-3","ISSN":"1475925X","PMID":"22236465","abstract":"BACKGROUND: Wireless capsule endoscopy has been introduced as an innovative, non-invasive diagnostic technique for evaluation of the gastrointestinal tract, reaching places where conventional endoscopy is unable to. However, the output of this technique is an 8 hours video, whose analysis by the expert physician is very time consuming. Thus, a computer assisted diagnosis tool to help the physicians to evaluate CE exams faster and more accurately is an important technical challenge and an excellent economical opportunity. METHOD: The set of features proposed in this paper to code textural information is based on statistical modeling of second order textural measures extracted from co-occurrence matrices. To cope with both joint and marginal non-Gaussianity of second order textural measures, higher order moments are used. These statistical moments are taken from the two-dimensional color-scale feature space, where two different scales are considered. Second and higher order moments of textural measures are computed from the co-occurrence matrices computed from images synthesized by the inverse wavelet transform of the wavelet transform containing only the selected scales for the three color channels. The dimensionality of the data is reduced by using Principal Component Analysis. RESULTS: The proposed textural features are then used as the input of a classifier based on artificial neural networks. Classification performances of 93.1% specificity and 93.9% sensitivity are achieved on real data. These promising results open the path towards a deeper study regarding the applicability of this algorithm in computer aided diagnosis systems to assist physicians in their clinical practice.","author":[{"dropping-particle":"","family":"Barbosa","given":"Daniel C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Roupar","given":"Dalila B.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ramos","given":"Jaime C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tavares","given":"Adriano C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lima","given":"Carlos S.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"BioMedical Engineering Online","id":"ITEM-1","issue":"1","issued":{"date-parts":[["2012"]]},"page":"3","publisher":"BioMed Central Ltd","title":"Automatic small bowel tumor diagnosis by using multi-scale wavelet-based analysis in wireless capsule endoscopy images","type":"article-journal","volume":"11"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>209</sup>","plainTextFormattedCitation":"209","previouslyFormattedCitation":"<sup>210</sup>"},"properties":{"noteIndex":0},"schema":""}20960020097.20%97.40%NR2009ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/IEMBS.2009.5334013","ISBN":"9781424432967","ISSN":"1557-170X","PMID":"19964706","abstract":"Traditional endoscopic methods do not allow the visualization of the entire Gastrointestinal (GI) tract. Wireless Capsule Endoscopy (CE) is a diagnostic procedure that overcomes this limitation of the traditional endoscopic methods. The CE video frames possess rich information about the condition of the stomach and intestine mucosa, encoded as color and texture patterns. It is known for a long time that human perception of texture is based in a multi-scale analysis of patterns, which can be modeled by multi-resolution approaches. Furthermore, modeling the covariance of textural descriptors has been successfully used in classification of colonoscopy videos. Therefore, in the present paper it is proposed a frame classification scheme based on statistical textural descriptors taken from the Discrete Curvelet Transform (DCT) domain, a recent multi-resolution mathematical tool. The DCT is based on an anisotropic notion of scale and high directional sensitivity in multiple directions, being therefore suited to characterization of complex patterns as texture. The covariance of texture descriptors taken at a given detail level, in different angles, is used as classification feature, in a scheme designated as Color Curvelet Covariance. The classification step is performed by a multilayer perceptron neural network. The proposed method has been applied in real data taken from several capsule endoscopic exams and reaches 97.2% of sensitivity and 97.4% specificity. These promising results support the feasibility of the proposed method.","author":[{"dropping-particle":"","family":"Barbosa","given":"Daniel J.C.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Ramos","given":"Jaime","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Correia","given":"José Higino","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lima","given":"Carlos S.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Proceedings of the 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society: Engineering the Future of Biomedicine, EMBC 2009","id":"ITEM-1","issued":{"date-parts":[["2009"]]},"page":"6683-6686","title":"Automatic detection of small bowel tumors in capsule endoscopy based on color curvelet covariance statistical texture descriptors","type":"article-journal"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>210</sup>","plainTextFormattedCitation":"210","previouslyFormattedCitation":"<sup>211</sup>"},"properties":{"noteIndex":0},"schema":""}210NR, not reported .FiguresFig. SEQ Fig. \* ARABIC 1 Examples of images obtained using alternative imaging technologies. a | In-Vitro imaging of porcine bowel using 39 MHz ultrasound capsule endoscopeADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/TMI.2017.2699973","ISBN":"2014061015185","ISSN":"0278-0062","author":[{"dropping-particle":"","family":"Wang","given":"Xingying","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Seetohul","given":"Vipin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Chen","given":"Ruimin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zhang","given":"Zhiqiang","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Qian","given":"Ming","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shi","given":"Zhehao","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Yang","given":"Ge","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Mu","given":"Peitian","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Wang","given":"Congzhi","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Huang","given":"Zhihong","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zhou","given":"Qifa","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Zheng","given":"Hairong","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cochran","given":"Sandy","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Qiu","given":"Weibao","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"IEEE Transactions on Medical Imaging","id":"ITEM-1","issue":"9","issued":{"date-parts":[["2017","9"]]},"page":"1922-1929","title":"Development of a Mechanical Scanning Device With High-Frequency Ultrasound Transducer for Ultrasonic Capsule Endoscopy","type":"article-journal","volume":"36"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>61</sup>","plainTextFormattedCitation":"61","previouslyFormattedCitation":"<sup>61</sup>"},"properties":{"noteIndex":0},"schema":""}61. b | Images of the duodenum in celiaccoeliac disease. The top panel was obtained using white light imaging and the bottom panel was obtained using narrow band imaging. Images courtesy of E. Toth. c | Image of polyps obtained using dye chromoendoscopy using 0.2% indigo carmine. Image courtesy of A. KoulaouzidisFig. SEQ Fig. \* ARABIC 2 Modalities for virtual biopsy. a | Cross-sectional image of intestinal villi captured using optical coherence tomograpyADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1364/BOE.8.002405","ISSN":"2156-7085","PMID":"28663882","abstract":"In this paper, we review the current state of technology development and clinical applications of endoscopic optical coherence tomography (OCT). Key design and engineering considerations are discussed for most OCT endoscopes, including side-viewing and forward-viewing probes, along with different scanning mechanisms (proximal-scanning versus distal-scanning). Multi-modal endoscopes that integrate OCT with other imaging modalities are also discussed. The review of clinical applications of endoscopic OCT focuses heavily on diagnosis of diseases and guidance of interventions. Representative applications in several organ systems are presented, such as in the cardiovascular, digestive, respiratory, and reproductive systems. A brief outlook of the field of endoscopic OCT is also discussed.","author":[{"dropping-particle":"","family":"Gora","given":"Michalina J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Suter","given":"Melissa J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Tearney","given":"Guillermo J.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Li","given":"Xingde","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Biomedical Optics Express","id":"ITEM-1","issue":"5","issued":{"date-parts":[["2017"]]},"page":"2405","title":"Endoscopic optical coherence tomography: technologies and clinical applications [Invited]","type":"article-journal","volume":"8"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>93</sup>","plainTextFormattedCitation":"93","previouslyFormattedCitation":"<sup>93</sup>"},"properties":{"noteIndex":0},"schema":""}93. b | OCT image of hyperplastic polyp ADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1002/jbio.200710017","ISBN":"1864-063X","ISSN":"1864063X","PMID":"19343643","abstract":"In the current paper we present results of application of endoscopic time-domain OCT (EOCT) with lateral scanning by forward looking miniprobe. We analysed material of clinical studies of 554 patients: 164 patients with urinary bladder pathology, and 390 with gastrointestinal tract pathology. We reviewed the materials obtained in different clinics using the OCT device elaborated at the Institute of Applied Physics. We demonstrate results of EOCT application in detection of early cancer and surgery guidance, examples of combined use of OCT and fluorescence imaging. As a result, we show the diagnostic accuracy of EOCT in specific clinical tasks. The sensitivity of EOCT cancer determination in Barrett's esophagus is from 71% to 85% at different stages of neoplasia with specificity 68% for all stages. As for bladder carcinoma, the sensitivity and specificity are 85% and 68%, respectively. In colon dysplasia EOST demonstrates high efficacy: sensitivity 92% and specificity 84%.","author":[{"dropping-particle":"","family":"Zagaynova","given":"E.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gladkova","given":"N.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Shakhova","given":"N.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gelikonov","given":"G.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Gelikonov","given":"V.","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"Journal of Biophotonics","id":"ITEM-1","issue":"2","issued":{"date-parts":[["2008"]]},"page":"114-128","title":"Endoscopic OCT with forward-looking probe: Clinical studies in urology and gastroenterology","type":"article-journal","volume":"1"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>171</sup>","plainTextFormattedCitation":"171","previouslyFormattedCitation":"<sup>172</sup>"},"properties":{"noteIndex":0},"schema":""}171 . c | A slide of haemotoxylin and eosin-stained porcine small bowel, which shows good agreement with a 47MHz micro-ultrasound scan of fresh frozen porcine bowel tissueADDIN CSL_CITATION {"citationItems":[{"id":"ITEM-1","itemData":{"DOI":"10.1109/ULTSYM.2015.0304","ISBN":"978-1-4799-8182-3","abstract":"Capsule endoscopy represents a highly convenient but limited means of imaging inflammatory conditions of the small bowel. The inclusion of high frequency microultrasound into a capsule endoscope has the potential to enhance diagnostic capabilities with subsurface imaging of the bowel wall. Experimental studies on abattoir-obtained porcine small bowel have been carried out as an ethical means to characterize healthy and altered tissue in a preclinical setting as well as to explore other means of imaging pathology. Samples of small bowel were cannulated and perfused with phosphate buffered saline followed by variable dilutions of polystyrene microspheres. All samples were scanned with a purpose built step scanner employing a 47 MHz single element transducer. Results indicated that tissue high frequency ultrasound demonstrated sufficient sensitivity to detect the disruption normal histology with microsphere infusion. The combination of microultrasound and capsule endoscopy has the potential to enhance the diagnostic capabilities with improved qualitative and quantitative dimensions.","author":[{"dropping-particle":"","family":"Cox","given":"Benjamin F.","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Seetohul","given":"Vipin","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Lay","given":"Holly","non-dropping-particle":"","parse-names":false,"suffix":""},{"dropping-particle":"","family":"Cochran","given":"Sandy","non-dropping-particle":"","parse-names":false,"suffix":""}],"container-title":"2015 IEEE International Ultrasonics Symposium (IUS)","id":"ITEM-1","issued":{"date-parts":[["2015","10"]]},"page":"1-4","publisher":"IEEE","title":"Microultraound and small bowel inflammation: Tissue phantom studies","type":"paper-conference"},"uris":[""]}],"mendeley":{"formattedCitation":"<sup>72</sup>","plainTextFormattedCitation":"72","previouslyFormattedCitation":"<sup>72</sup>"},"properties":{"noteIndex":0},"schema":""}72 Box 1 White light imaging capsule endoscopy is limited to surface visualization and limited specificity of diagnosis due to similarities in the mucosal appearance of different small bowel diseases. Research and development of non-white light imaging capsules has increased in recent years.Some of these non-WLI capsules are now commercially available, such as the SmartPill.Most of the non-WLI capsules are still at the prototype stage, and the diagnostic efficacy of their sensing and imaging modalities, as well as their cost-benefit ratio needs to be validated through extensive clinical trials. Non-WLI capsules capable of measuring pH, pressure changes, concentration of chemicals and much more have been developed.One challenge of WLI and non-WLI CE is the need for accurate means of determining the position of the capsule at all times to enable the localization of pathologies for subsequent follow-up.Non-WLI capsules such as those capable of OCT or micro-ultrasound have the potential to provide CE with the capability of providing real-time, in vivo, high-resolution transmural imaging that could remove the need for tissue biopsy. One challenge for clinicians in the future will be the increasing amount of data that will need to be reviewed for diagnosis due to the increased use of WLI and non-WLI CE. This challenge has spurred research into computer aided diagnosis (CADx), whereby algorithms are used to automate the identification and interpretation of pathologiesThe lack of standardized data-sets has impeded the accurate comparison of various CADx algorithms.CADx may require the use of multiple modalities in non-WLI CE to improve accuracy and specificity, which will require challenges related to miniaturization, integration and power consumption of CE systems to be overcome. GlossaryCompton Scattering: The scattering of a photon by a charge particle that results in a decrease in energy of the photon.Cyclic Voltammetry: A type of voltammetric experiment where the potential is varied as a linear function of time. It is one of the most commonly used electrochemical techniques. Micro-cancersPhotobleaching: The permanent loss of fluorescence in a fluorophore due to photon-induced chemical damagePotentiostatic circuit: An electronic circuit that enables the control of the voltage difference between electrodes in an electrochemical cell. Pulse Voltammetry: A type of voltammetric experiment where the varying potential consists of a series of increasing amplitude, with the potential returning to the initial value after each pulse. Quantum yield: Quantum yield refers to the number of times a specific event occurs per photon absorbed by the system in a radiation induced process. Single element transducer: A device that generally consists of a piezoelectric material housed in a casing that can both transmit and receive ultrasound signals. Voltammetry: An electrochemical experiment used to identify a substance by how the current flowing through it changes as the potential is changed.Voltammograms: A plot of cell current versus. the potential arising from a Voltammetry experimentVolumetric Imaging: A sequence of 2D images that are grouped together to form a 3D image of a volume of spaceReferencesADDIN Mendeley Bibliography CSL_BIBLIOGRAPHY 1.Enns, R. A. et al. Clinical Practice Guidelines for the Use of Video Capsule?Endoscopy. Gastroenterology 152, 497–514 (2017).2.Koulaouzidis, A., Iakovidis, D. K., Karargyris, A. & Rondonotti, E. Wireless endoscopy in 2020: Will it still be a capsule? World J. Gastroenterol. 21, 5119–5130 (2015).3.Cox, B. F. B. F. et al. Ultrasound capsule endoscopy: sounding out the future. Ann. Transl. Med. 5, 201–201 (2017).4.Lay, H. et al. In-Vivo Evaluation of Microultrasound and Thermometric Capsule Endoscopes. IEEE Trans. Biomed. Eng. 66, 632–639 (2018).5.Zhang, H. et al. 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