Spiral.imperial.ac.uk



The Influence of Inspiratory Effort and Emphysema on Pulmonary Nodule Volumetry ReproducibilityIntroductionPulmonary nodule volumetry applications have played a central role in the nodule management algorithms of several European lung cancer screening trialsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/thoraxjnl-2011-200736", "ISSN" : "1468-3296 (Electronic)", "PMID" : "22286927", "abstract" : "BACKGROUND: The effects of low-dose CT screening on disease stage shift, mortality and overdiagnosis are unclear. Lung cancer findings and mortality rates are reported at the end of screening in the Danish Lung Cancer Screening Trial. METHODS: 4104 men and women, healthy heavy smokers/former smokers were randomised to five annual low-dose CT screenings or no screening. Two experienced chest radiologists read all CT scans and registered the location, size and morphology of nodules. Nodules between 5 and 15 mm without benign characteristics were rescanned after 3 months. Growing nodules (>25% volume increase and/or volume doubling time<400 days) and nodules >15 mm were referred for diagnostic workup. In the control group, lung cancers were diagnosed and treated outside the study by the usual clinical practice. RESULTS: Participation rates were high in both groups (screening: 95.5%; control: 93.0%; p<0.001). Lung cancer detection rate was 0.83% at baseline and mean annual detection rate was 0.67% at incidence rounds (p=0.535). More lung cancers were diagnosed in the screening group (69 vs. 24, p<0.001), and more were low stage (48 vs 21 stage I-IIB non-small cell lung cancer (NSCLC) and limited stage small cell lung cancer (SCLC), p=0.002), whereas frequencies of high-stage lung cancer were the same (21 vs 16 stage IIIA-IV NSCLC and extensive stage SCLC, p=0.509). At the end of screening, 61 patients died in the screening group and 42 in the control group (p=0.059). 15 and 11 died of lung cancer, respectively (p=0.428). CONCLUSION: CT screening for lung cancer brings forward early disease, and at this point no stage shift or reduction in mortality was observed. More lung cancers were diagnosed in the screening group, indicating some degree of overdiagnosis and need for longer follow-up.", "author" : [ { "dropping-particle" : "", "family" : "Saghir", "given" : "Zaigham", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dirksen", "given" : "Asger", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ashraf", "given" : "Haseem", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bach", "given" : "Karen Skjoldstrup", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brodersen", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clementsen", "given" : "Paul Frost", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dossing", "given" : "Martin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansen", "given" : "Hanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kofoed", "given" : "Klaus Fuglsang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Larsen", "given" : "Klaus Richter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mortensen", "given" : "Jann", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rasmussen", "given" : "Jakob Fraes", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seersholm", "given" : "Niels", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Skov", "given" : "Birgit Guldhammer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thorsen", "given" : "Hanne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tonnesen", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pedersen", "given" : "Jesper Holst", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Thorax", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012", "4" ] ] }, "language" : "eng", "page" : "296-301", "publisher-place" : "England", "title" : "CT screening for lung cancer brings forward early disease. The randomised Danish Lung Cancer Screening Trial: status after five annual screening rounds with low-dose CT.", "type" : "article-journal", "volume" : "67" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1183/09031936.00197712", "ISBN" : "0031107044", "ISSN" : "09031936", "PMID" : "23845716", "abstract" : "Several medical associations recommended lung cancer screening by low-dose computed tomography scanning for high-risk groups. Counselling of the candidates on the potential harms and benefits and their lung cancer risk is a prerequisite for screening. In the NELSON trial, screenings are considered positive for (part) solid lung nodules with a volume >500 mm3 and for (part) solid or nonsolid nodules with a volume-doubling time <400 days. For this study, the performance of the NELSON strategy in three screening rounds was evaluated and risk calculations were made for a follow-up period of 5.5 years. 458 (6%) of the 7582 participants screened had a positive screen result and 200 (2.6%) were diagnosed with lung cancer. The positive screenings had a predictive value of 40.6% and only 1.2% of all scan results were false-positive. In a period of 5.5 years, the risk of screen-detected lung cancer strongly depends on the result of the first scan: 1.0% after a negative baseline result, 5.7% after an indeterminate baseline and 48.3% after a positive baseline. The screening strategy yielded few positive and false-positive scans with a reasonable positive predictive value. The 5.5-year lung cancer risk calculations aid clinicians in counselling candidates for lung cancer screening with low-dose computed tomography.", "author" : [ { "dropping-particle" : "", "family" : "Horeweg", "given" : "Nanda", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aalst", "given" : "Carlijn M.", "non-dropping-particle" : "Van Der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vliegenthart", "given" : "Rozemarijn", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Yingru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Xie", "given" : "Xueqian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scholten", "given" : "Ernst Th", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mali", "given" : "Willem", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Thunnissen", "given" : "Erik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weenink", "given" : "Carla", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groen", "given" : "Harry J M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lammers", "given" : "Jan Willem J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nackaerts", "given" : "Kristiaan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosmalen", "given" : "Joost", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oudkerk", "given" : "Matthijs", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koning", "given" : "Harry J.", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Respiratory Journal", "id" : "ITEM-2", "issue" : "6", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "1659-1667", "title" : "Volumetric computed tomography screening for lung cancer: Three rounds of the NELSON trial", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1136/thoraxjnl-2015-207140", "abstract" : "Background Lung cancer screening using low-dose CT (LDCT) was shown to reduce lung cancer mortality by 20% in the National Lung Screening Trial.Methods The pilot UK Lung Cancer Screening (UKLS) is a randomised controlled trial of LDCT screening for lung cancer versus usual care. A population-based questionnaire was used to identify high-risk individuals. CT screen-detected nodules were managed by a pre-specified protocol. Cost effectiveness was modelled with reference to the National Lung Cancer Screening Trial mortality reduction.Results 247\u2005354 individuals aged 50\u201375\u2005years were approached; 30.7% expressed an interest, 8729 (11.5%) were eligible and 4055 were randomised, 2028 into the CT arm (1994 underwent a CT). Forty-two participants (2.1%) had confirmed lung cancer, 34 (1.7%) at baseline and 8 (0.4%) at the 12-month scan. 28/42 (66.7%) had stage I disease, 36/42 (85.7%) had stage I or II disease. 35/42 (83.3%) had surgical resection. 536 subjects had nodules greater than 50\u2005mm3 or 5\u2005mm diameter and 41/536 were found to have lung cancer. One further cancer was detected by follow-up of nodules between 15 and 50\u2005mm3 at 12\u2005months. The baseline estimate for the incremental cost-effectiveness ratio of once-only CT screening, under the UKLS protocol, was \u00a38466 per quality adjusted life year gained (CI \u00a35542 to \u00a312\u2005569).Conclusions The UKLS pilot trial demonstrated that it is possible to detect lung cancer at an early stage and deliver potentially curative treatment in over 80% of cases. Health economic analysis suggests that the intervention would be cost effective\u2014this needs to be confirmed using data on observed lung cancer mortality reduction.Trial registration ISRCTN 78513845. ", "author" : [ { "dropping-particle" : "", "family" : "Field", "given" : "J K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Duffy", "given" : "S W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baldwin", "given" : "D R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Whynes", "given" : "D K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Devaraj", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brain", "given" : "K E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Eisen", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gosney", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Green", "given" : "B A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Holemans", "given" : "J A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kavanagh", "given" : "T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kerr", "given" : "K M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ledson", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lifford", "given" : "K J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McRonald", "given" : "F E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nair", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Page", "given" : "R D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Parmar", "given" : "M K B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rassl", "given" : "D M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rintoul", "given" : "R C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Screaton", "given" : "N J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wald", "given" : "N J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weller", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williamson", "given" : "P R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yadegarfar", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hansell", "given" : "D M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Thorax ", "id" : "ITEM-3", "issued" : { "date-parts" : [ [ "2015", "12", "8" ] ] }, "note" : "10.1136/thoraxjnl-2015-207140", "title" : "UK Lung Cancer RCT Pilot Screening Trial: baseline findings from the screening arm provide evidence for the potential implementation of lung cancer screening", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1097/CEJ.0b013e328351e1b6", "ISSN" : "1473-5709 (Electronic)", "PMID" : "22465911", "abstract" : "The efficacy and cost-effectiveness of low-dose spiral computed tomography (LDCT) screening in heavy smokers is currently under evaluation worldwide. Our screening program started with a pilot study on 1035 volunteers in Milan in 2000 and was followed up in 2005 by a randomized trial comparing annual or biennial LDCT with observation, named Multicentric Italian Lung Detection. This included 4099 participants, 1723 randomized to the control group, 1186 to biennial LDCT screening, and 1190 to annual LDCT screening. Follow-up was stopped in November 2011, with 9901 person-years for the pilot study and 17 621 person-years for Multicentric Italian Lung Detection. Forty-nine lung cancers were detected by LDCT (20 in biennial and 29 in the annual arm), of which 17 were identified at baseline examination; 63% were of stage I and 84% were surgically resectable. Stage distribution and resection rates were similar in the two LDCT arms. The cumulative 5-year lung cancer incidence rate was 311/100 000 in the control group, 457 in the biennial, and 620 in the annual LDCT group (P=0.036); lung cancer mortality rates were 109, 109, and 216/100 000 (P=0.21), and total mortality rates were 310, 363, and 558/100 000, respectively (P=0.13). Total mortality in the pilot study was similar to that observed in the annual LDCT arm at 5 years. There was no evidence of a protective effect of annual or biennial LDCT screening. Furthermore, a meta-analysis of the four published randomized trials showed similar overall mortality in the LDCT arms compared with the control arm.", "author" : [ { "dropping-particle" : "", "family" : "Pastorino", "given" : "Ugo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rossi", "given" : "Marta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosato", "given" : "Valentina", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marchiano", "given" : "Alfonso", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sverzellati", "given" : "Nicola", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Morosi", "given" : "Carlo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fabbri", "given" : "Alessandra", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Galeone", "given" : "Carlotta", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Negri", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sozzi", "given" : "Gabriella", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pelosi", "given" : "Giuseppe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vecchia", "given" : "Carlo", "non-dropping-particle" : "La", "parse-names" : false, "suffix" : "" } ], "container-title" : "European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)", "id" : "ITEM-4", "issue" : "3", "issued" : { "date-parts" : [ [ "2012", "5" ] ] }, "language" : "eng", "page" : "308-315", "publisher-place" : "England", "title" : "Annual or biennial CT screening versus observation in heavy smokers: 5-year results of the MILD trial.", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[1\u20134]", "plainTextFormattedCitation" : "[1\u20134]", "previouslyFormattedCitation" : "[1\u20134]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[1–4]. Semi-automated nodule volumetry offers benefits compared to manual electronic caliper diameter measurements as it is more reproducibleADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1148/radiol.2312030241", "ISBN" : "2312030241", "ISSN" : "0033-8419", "PMID" : "15128991", "abstract" : "PURPOSE: To evaluate software designed to calculate pulmonary nodule volume in three dimensions. MATERIALS AND METHODS: Fifty-four solid noncalcified pulmonary nodules measuring 5-18 mm in diameter were studied with computed tomographic (CT) volumetric software. Baseline CT examinations were performed for various indications by using four-detector row multisection CT units, 1.25- or 2.50-mm sections, and a standard reconstruction algorithm. The percentage of successful nodule segmentations, as well as intraobserver variability, interreader agreement, and global repeatability of calculated volumes, was determined on the basis of consecutive measurements performed three times by three different radiologists by using the Bland and Altman method. The software was used to calculate the doubling time of 22 nodules for which a final diagnosis and comparable CT scans were available. RESULTS: Fifty-two (96%) of the 54 nodules were successfully segmented, allowing their volume to be calculated. Repeatability was high: There was no variation in the nine measurements of 35 (67%) of the 52 nodules. The coefficient of variation for the remaining 17 nodules (33%) was 2.26%. Bland and Altman 95% limits of acceptability, calculated on the basis of log-transformed data, yielded a maximum software measurement error of 6.38% of the previous volume measurement. Doubling time ranged from 4 to 188 years for the 13 benign nodules and from 37 to 216 days for the nine malignant nodules. CONCLUSION: Software volumetric analysis yielded repeatable estimates for 96% of the nodules examined. All software-calculated doubling times were in keeping with the benign or malignant nature of the nodules.", "author" : [ { "dropping-particle" : "", "family" : "Revel", "given" : "Marie-Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lefort", "given" : "Catherine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bissery", "given" : "Alvine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bienvenu", "given" : "Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aycard", "given" : "Laetitia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chatellier", "given" : "Gilles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frija", "given" : "Guy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Radiology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "459-466", "title" : "Pulmonary nodules: preliminary experience with three-dimensional evaluation.", "type" : "article-journal", "volume" : "231" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1148/radiol.2312030167", "ISSN" : "0033-8419", "PMID" : "15128990", "abstract" : "PURPOSE: To evaluate the intra- and interreader agreement of two-dimensional computed tomographic (CT) measurements of pulmonary nodules less than 2 cm in diameter. MATERIALS AND METHODS: Three readers independently made three serial measurements of each of 54 pulmonary nodules measuring 3-18 mm that had been observed on standard-dose multisection CT images obtained in 24 patients who ranged in age from 36 to 81 years (mean age, 54.6 years). There were 14 women (58%), who ranged in age from 43 to 81 years (mean age, 58.9 years), and 10 men (42%), who ranged in age from 36 to 65 years (mean age, 48.5 years). The largest transverse cross-sectional diameter of each nodule was measured at picture archiving and communication system, or PACS, workstations by using high-spatial-resolution reconstructed CT images and identical window settings. Intra- and interreader agreement were determined by using methods described by Bland and Altman: the coefficient of repeatability for intrareader agreement, and methods derived from the 95% limits of agreement defined by Bland and Altman for interreader agreement. RESULTS: The repeatability coefficients were 1.70, 1.32, and 1.51 mm for readers 1, 2, and 3, respectively. The 95% limits of agreement for the difference among readers were -1.73 and 1.73. CONCLUSION: Two-dimensional CT measurements are not reliable in the evaluation of small noncalcified pulmonary nodules.", "author" : [ { "dropping-particle" : "", "family" : "Revel", "given" : "Marie-Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bissery", "given" : "Alvine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bienvenu", "given" : "Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aycard", "given" : "Laetitia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lefort", "given" : "Catherine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frija", "given" : "Guy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Radiology", "id" : "ITEM-2", "issue" : "2", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "453-458", "title" : "Are two-dimensional CT measurements of small noncalcified pulmonary nodules reliable?", "type" : "article-journal", "volume" : "231" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[5, 6]", "plainTextFormattedCitation" : "[5, 6]", "previouslyFormattedCitation" : "[5, 6]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[5, 6]. Superior reproducibility is of paramount importance if true nodule growth is to be distinguished from spurious measurement imprecision. Furthermore, volumetry can be used to calculate nodule volume doubling times (VDT) on serial CT scans. Recently, volumetry and the VDT have been integrated into clinical guidelines for the investigation of pulmonary nodules issued by the British Thoracic SocietyADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/thoraxjnl-2015-207168", "author" : [ { "dropping-particle" : "", "family" : "Callister", "given" : "M E J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Baldwin", "given" : "D R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Akram", "given" : "A R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Barnard", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cane", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Draffan", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Franks", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gleeson", "given" : "F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graham", "given" : "R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Malhotra", "given" : "P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokop", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rodger", "given" : "K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Subesinghe", "given" : "M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Waller", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Woolhouse", "given" : "I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Group", "given" : "British Thoracic Society Pulmonary Nodule Guideline Development", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Thorax ", "id" : "ITEM-1", "issue" : "Suppl 2 ", "issued" : { "date-parts" : [ [ "2015", "8", "1" ] ] }, "note" : "10.1136/thoraxjnl-2015-207168", "page" : "ii1-ii54", "title" : "British Thoracic Society guidelines for the investigation and management of pulmonary nodules: accredited by NICE", "type" : "article-journal", "volume" : "70 " }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[7]", "plainTextFormattedCitation" : "[7]", "previouslyFormattedCitation" : "[7]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[7].Reproducible pulmonary nodule volumetry requires successful nodule segmentation, a process that in part relies on predefined density thresholdsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1118/1.598605", "ISSN" : "0094-2405 (Print)", "PMID" : "10436889", "abstract" : "A multi-criterion algorithm for automatic delineation of small pulmonary nodules on helical CT images has been developed. In a slice-by-slice manner, the algorithm uses density, gradient strength, and a shape constraint of the nodule to automatically control segmentation process. The multiple criteria applied to separation of the nodule from its surrounding structures in lung are based on the fact that typical small pulmonary nodules on CT images have high densities, show a distinct difference in density at the boundary, and tend to be compact in shape. Prior to the segmentation, a region-of-interest containing the nodule is manually selected on the CT images. Then the segmentation process begins with a high density threshold that is decreased stepwise, resulting in expansion of the area of nodule candidates. This progressive region growing approach is terminated when subsequent thresholds provide either a diminished gradient strength of the nodule contour or significant changes of nodule shape from the compact form. The shape criterion added to the algorithm can effectively prevent the high density surrounding structures (e.g., blood vessels) from being falsely segmented as nodule, which occurs frequently when only the gradient strength criterion is applied. This has been demonstrated by examples given in the Results section. The algorithm's accuracy has been compared with that of radiologist's manual segmentation, and no statistically significant difference has been found between the nodule areas delineated by radiologist and those obtained by the multi-criterion algorithm. The improved nodule boundary allows for more accurate assessment of nodule size and hence nodule growth over a short time period, and for better characterization of nodule edges. This information is useful in determining malignancy status of a nodule at an early stage and thus provides significant guidance for further clinical management.", "author" : [ { "dropping-particle" : "", "family" : "Zhao", "given" : "B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yankelevitz", "given" : "D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reeves", "given" : "A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Henschke", "given" : "C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Medical physics", "id" : "ITEM-1", "issue" : "6", "issued" : { "date-parts" : [ [ "1999", "6" ] ] }, "language" : "eng", "page" : "889-895", "publisher-place" : "UNITED STATES", "title" : "Two-dimensional multi-criterion segmentation of pulmonary nodules on helical CT images.", "type" : "article-journal", "volume" : "26" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[8]", "plainTextFormattedCitation" : "[8]", "previouslyFormattedCitation" : "[8]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[8]. Segmentation is, therefore, potentially affected by the density of lung surrounding a nodule - a factor that is in turn inevitably influenced by inspiratory level and the presence of any emphysema adjacent to the noduleADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00330-014-3418-0", "ISSN" : "1432-1084 (Electronic)", "PMID" : "25218764", "abstract" : "OBJECTIVES: One objective was to evaluate the air trapping index (ATI), measured by inspiration/expiration CT, in COPD patients and nonsmokers. Another objective was to assess the association between the pulmonary function test (PFT) and CT parameters such as ATI or other indices, separately in the whole lung, in emphysema, and in hyperinflated and normal lung areas. METHODS: One hundred and thirty-eight COPD patients and 29 nonsmokers were included in our study. The ATI, the emphysema index (EI), the gas trapping index (Exp -856) and expiration/inspiration ratio of mean lung density (E/Iratio of MLD) were measured on CT. The values of the whole lung, of emphysema, and of hyperinflated and normal lung areas were compared and then correlated with various PFT parameters. RESULTS: Compared with nonsmokers, COPD patients showed a higher ATI in the whole lung and in each lung lesion (all P < 0.05). The ATI showed a higher correlation than EI with FEF25-75%, RV and RV/TLC, and was comparable to Exp -856 and the E/I ratio of MLD. The ATI of emphysema and hyperinflated areas on CT showed better correlation than the normal lung area with PFT parameters. CONCLUSIONS: Detailed analysis of density change at inspiration and expiration CT of COPD can provide new insights into pulmonary functional impairment in each lung area. KEY POINTS: * COPD patients show significant air trapping in the lung. * The air trapping index is a comparable parameter to other CT indices. * Air trapping of emphysema and hyperinflated lung areas relates to functional loss. * The emphysema area changes more, with less air trapping than other areas.", "author" : [ { "dropping-particle" : "", "family" : "Kim", "given" : "Eun Young", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Seo", "given" : "Joon Beom", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Hyun Joo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Namkug", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Eunsol", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Sang Min", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oh", "given" : "Sang Young", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hwang", "given" : "Hye Jeon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oh", "given" : "Yeon-Mok", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Sang-Do", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European radiology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2015", "2" ] ] }, "language" : "eng", "page" : "541-549", "publisher-place" : "Germany", "title" : "Detailed analysis of the density change on chest CT of COPD using non-rigid registration of inspiration/expiration CT scans.", "type" : "article-journal", "volume" : "25" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[9]", "plainTextFormattedCitation" : "[9]", "previouslyFormattedCitation" : "[9]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[9]. However, there is little data concerning the effects of inspiratory effort and local emphysema on nodule volumetry reproducibility. Furthermore, the limited data that is available, particularly regarding inspiratory effort, is conflictingADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1229-6929", "PMID" : "17143027", "abstract" : "OBJECTIVE: To evaluate how changes in lung volume affect volumetric measurements of lung nodules using a multi-detector row CT. MATERIALS AND METHODS: Ten subjects with asthma or chronic bronchitis who had one or more lung nodules were included. For each subject, two sets of CT images were obtained at inspiration and at expiration. A total of 33 nodules (23 nodules > or =3 mm) were identified and their volume measured using a semiautomatic volume measurement program. Differences between nodule volume on inspiration and expiration were compared using the paired t-test. Percent differences, between on inspiration and expiration, in nodule attenuation, total lung volume, whole lung attenuation, and regional lung attenuation, were computed and compared with percent difference in nodule volume determined by linear correlation analysis. RESULTS: The difference in nodule volume observed between inspiration and expiration was significant (p < 0.01); the mean percent difference in lung nodule volume was 23.1% for all nodules and for nodules > or =3 mm. The volume of nodules was measured to be larger on expiration CT than on inspiration CT (28 out of 33 nodules; 19 out of 23 nodules > or =3 mm). A statistically significant correlation was found between the percent difference of lung nodule volume and lung volume or regional lung attenuation (p < 0.05) for nodules > or =3 mm. CONCLUSION: Volumetric measurements of pulmonary nodules were significantly affected by changes in lung volume. The variability in this respiration-related measurement should be considered to determine whether growth has occurred in a lung nodule.", "author" : [ { "dropping-particle" : "", "family" : "Goo", "given" : "Jin Mo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Kwang Gi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gierada", "given" : "David S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Castro", "given" : "Mario", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bae", "given" : "Kyongtae T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Korean journal of radiology : official journal of the Korean Radiological Society", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "243-248", "title" : "Volumetric measurements of lung nodules with multi-detector row CT: effect of changes in lung volume.", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1016/j.acra.2007.01.008", "ISSN" : "1076-6332 (Print)", "PMID" : "17368218", "abstract" : "RATIONALE AND OBJECTIVES: We sought to determine how measures of nodule diameter and volume on computed tomography (CT) vary with changes in inspiratory level. MATERIALS AND METHODS: CT scans were performed with inspiration suspended at total lung capacity (TLC) and then at residual volume (RV) in 41 subjects, in whom 75 indeterminate lung nodules were detected. A fully automated contouring program was used to segment the lungs; followed by segmentation of all nodules and the corresponding lobe using semiautomated contouring in both TLC and RV scans. The percent changes in lung and lobar volumes between TLC and RV were correlated with percent changes in nodule diameters and volumes. RESULTS: Both nodule diameter and volume varied nonuniformly from TLC to RV-some nodules decreased in size, while others increased. There was a 16.8% mean change in absolute volume across all nodules. Stratified by size, the mean value of the absolute percent volume changes for nodules > or =5 mm and <5 mm were not significantly different (P = .26). Stratified by maximum attenuation, the mean value of the absolute percent volume changes between the TLC and RV series for noncalcified (17.7%, SD = 13.1) and completely calcified nodules (8.6% SD = 5.7) were significantly different (P < .05). CONCLUSION: Significant differences in nodule size were measured between TLC and RV scans. This has important implications for standardizing acquisition protocols in any setting where size and, more important, size change are being used for purposes of lung cancer staging, nodule characterization, or treatment response assessment.", "author" : [ { "dropping-particle" : "", "family" : "Petkovska", "given" : "Iva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "Matthew S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldin", "given" : "Jonathan G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Hyun J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McNitt-Gray", "given" : "Michael F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abtin", "given" : "Fereidoun G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghurabi", "given" : "Raffi J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aberle", "given" : "Denise R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Academic radiology", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2007", "4" ] ] }, "language" : "eng", "page" : "476-485", "publisher-place" : "United States", "title" : "The effect of lung volume on nodule size on CT.", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1148/radiol.2452061054", "ISBN" : "10.1148/radiol.2452061054", "ISSN" : "0033-8419", "PMID" : "17923508", "abstract" : "PURPOSE: To prospectively assess the precision of semiautomated volume measurements of pulmonary nodules at low-dose multi-detector row computed tomography (CT) and to investigate the influence of nodule size, segmentation algorithm, and inspiration level. MATERIALS AND METHODS: This study had institutional review board approval; written informed consent was obtained from all patients. Between June 2004 and March 2005, 20 patients (15 men, five women; age range, 40-84 years; mean age, 57 years) referred for chest CT for known lung metastases underwent two additional low-dose chest CT examinations without contrast material (collimation, 16 x 0.75 mm). Between these examinations, patients got off and on the table to simulate the conditions for a follow-up examination. Noncalcified solid pulmonary nodules between 15 and 500 mm(3) that did not abut vessel or pleura were measured in both studies by using widely applied commercial semiautomated software. Interscan variability was established with the Bland and Altman approach. The impact of nodule shape (spherical or nonspherical) on measurement variability was assessed by using one-way analysis of variance, while the contributions of mean nodule volume and change in lung volume were investigated with univariate linear regression for completely (group A) and incompletely (group B) segmented nodules. RESULTS: Two hundred eighteen eligible nodules (volume range, 16.4-472.7 mm(3); 106 spherical, 112 nonspherical) were evaluated. The 95% confidence interval for difference in measured volumes was -21.2%, 23.8% (mean difference, 1.3%). The precision of nodule segmentation was highly dependent on nodule shape (P < .001) and was weakly related to inspiration level for completely segmented nodules (r = -0.20; P < .047), while mean nodule volume did not show any effect (P = .15 and P = .81 for group A and B nodules, respectively). CONCLUSION: Variation of semiautomated volume measurements of pulmonary nodules can be substantial. Segmentation represents the most important factor contributing to measurement variability, while change in inspiration level has only a weak effect for completely segmented nodules.", "author" : [ { "dropping-particle" : "", "family" : "Gietema", "given" : "Hester a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schaefer-Prokop", "given" : "Cornelia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mali", "given" : "Willem P T M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groenewegen", "given" : "Gerard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokop", "given" : "Mathias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Radiology", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "888-894", "title" : "Pulmonary nodules: Interscan variability of semiautomated volume measurements with multisection CT-- influence of inspiration level, nodule size, and segmentation performance.", "type" : "article-journal", "volume" : "245" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[10\u201312]", "plainTextFormattedCitation" : "[10\u201312]", "previouslyFormattedCitation" : "[10\u201312]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[10–12], and has resulted in calls for further clarificationADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1148/radiographics.29.2.0290637", "ISSN" : "0271-5333", "author" : [ { "dropping-particle" : "", "family" : "Hochhegger", "given" : "Bruno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "RadioGraphics", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2009", "3", "1" ] ] }, "note" : "doi: 10.1148/radiographics.29.2.0290637", "page" : "637-638", "publisher" : "Radiological Society of North America", "title" : "Re: Respiratory Instructions for CT Examinations of the Lungs", "type" : "article-journal", "volume" : "29" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[13]", "plainTextFormattedCitation" : "[13]", "previouslyFormattedCitation" : "[13]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[13]. In this study, we aimed to assess interscan variability by testing the ability to detect the absence of nodule growth between two scans performed on the same day, in which any perceived difference in nodule volume can be attributed to imperfect reproducibility (i.e. interscan variability). Specifically, we investigated the effect of inspiratory effort on volumetry reproducibility by comparing nodule volumes on full-inspiratory versus end-expiratory CT scans. Additionally, we investigated whether the degree of variability was influenced by the presence of emphysema local to the nodule. Materials and MethodsPatient SelectionThis retrospective study had institutional review board approval and patient consent was not required. Baseline full-inspiratory and end-expiratory CT scans undertaken on the same attendance for patients with severe emphysema under consideration for bronchoscopic lung volume reduction as part of a bronchoscopic lung volume reduction trial were retrospectively reviewed. CTs in which lung nodules were reported were selected for the study. The final study population comprised 88 nodules in 24 patients with emphysema (mean age: 64 years; range: 49 – 79 years; 20 [83%] male).Image AcquisitionFull-inspiratory and end-expiratory scans were undertaken on the same attendance. Patients remained supine on the scanner between acquisitions. All scans were performed without contrast media on a 128 detector row scanner (Somatom Definition Edge, Siemens, Erlangen, Germany). CTs were acquired using 120 kVp tube voltage, 70-110 mAs according to body habitus (patients weighing less than 50 kg received 70mAs; 50-90 kg :90 mAs; >90kg :110 mAs) with dose modulation turned off, 0.5 s rotation time, 128 x 0.6 mm collimation, pitch 0.8. Images were reconstructed using a medium kernel (B40f), 1 mm slice thickness and 1 mm increment.Nodule VolumetryCTs were analysed by a radiologist using the Oncology package on SyngoVia version VA30A (Siemens, Erlangen, Germany). Using the inspiratory axial dataset, non-calcified solid pulmonary nodules identified in the CT report were confirmed and measured by a radiologist and any additional solid non-calcified nodules ≥15mm 3 were also recorded and measured. Nodules were individually recorded by slice number and lobe. Nodule size was evaluated using semi-automatic nodule volumetry, requiring the radiologist to place a ‘seed point’ within the nodule. This provided an inspiratory nodule volume (mm3). Corresponding nodules were identified on the expiratory series and expiratory nodule volumes were similarly calculated. Nodules where segmentation was judged to be unsatisfactory on inspiratory CT were excluded.Local Emphysema CalculationLocal emphysema calculation was performed by a radiologist using the inspiratory dataset, also employing SyngoVia Oncology package (Siemens, Erlangen, Germany). A segmentation region of interest was manually drawn circumferentially around each nodule, extending approximately 1 cm beyond the edge of the nodule, taking care to avoid adjacent bronchial, pleural or vascular structures. The volume of the segmented region with a density of ≤ -950 HU, taken to represent emphysemaADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00330-012-2683-z", "ISSN" : "0938-7994", "abstract" : "OBJECTIVES: To determine the optimal threshold by quantitatively assessing the extent of emphysema at the level of the entire lung and at the level of individual lobes using a large, diverse dataset of CT examinations. METHODS: This study comprises 573 chest CT examinations acquired from different subjects (222 none, 83 mild, 141 moderate, 63 severe, and 64 very severe obstruction). The extent of emphysema was quantified using the percentage of the low attenuation area (LAA%) divided by the total lung or lobe volume(s). The correlations between the extent of emphysema, and pulmonary functions and the five-category classification were assessed using Pearson and Spearman\u2019s correlation coefficients, respectively. When quantifying emphysema using a density mask, a wide range of thresholds from \u2212850 to \u22121000 HU were used. RESULTS: The highest correlations of LAA% with the five-category classification and PFT measures ranged from \u2212925 to \u2212965 HU for each individual lobe and the entire lung. However, the differences between the highest r and those obtained at \u2212950 HU are relatively small. CONCLUSION: Although there are variations in the optimal cut-off thresholds for individual lobes, the single threshold of \u2212950 HU is still an acceptable threshold for density-based emphysema quantification. ", "author" : [ { "dropping-particle" : "", "family" : "Wang", "given" : "Zhimin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gu", "given" : "Suicheng", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Leader", "given" : "Joseph K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kundu", "given" : "Shinjini", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tedrow", "given" : "John R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sciurba", "given" : "Frank C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gur", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siegfried", "given" : "Jill M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pu", "given" : "Jiantao", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European radiology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2013", "4", "1" ] ] }, "page" : "975-984", "title" : "Optimal Threshold in CT Quantification of Emphysema", "type" : "article-journal", "volume" : "23" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[14]", "plainTextFormattedCitation" : "[14]", "previouslyFormattedCitation" : "[14]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[14], was automatically calculated by using a “Hounsfield Unit Statistics” function within the Oncology application. By subtracting the known volume of the nodule, the percentage of surrounding lung with a density of ≤ -950 HU could be obtained – this constituted local emphysema extent (Figure 1). A second radiologist also measured local emphysema extent so as to quantify inter-observer variation.Inspiratory and Expiratory Lung Volumes and overall emphysema extentLung volumes on inspiratory and expiratory scans were calculated automatically using Pulmo 3D on SyngoVia (Siemens, Erlangen, Germany). The percentage reduction in lung volume at expiration was calculated. The same software was also used to quantify overall total lung emphysema extent using -950HU cut-off.StatisticsDifferences in inspiratory and expiratory nodule volume were compared using Bland-Altman statistics. The influences of nodule size, percentage reduction in lung volume at expiration, and local emphysema extent on nodule volume variability were tested with multiple linear regression. Differences in nodule volume change between lobar location of nodules was evaluated using t-test.Interobserver agreement for absolute extent of local emphysema was tested using interclass correlation co-efficient. Weighted kappa statistic was used to assess observer agreement for severity of local emphysema within the region of interest, whereby local emphysema severity was graded, post hoc, into 5 evenly distributed groups: group 0 = no emphysema, group 1 = emphysema between > 0% and < 10%, group 2 = between 10% and 20%, group 3= between 20% and 30%, group 4 = between 30% and 40%, group 5 ≥ 40%. Medcalc statistical software was used for all statistical analyses.ResultsEight nodules were excluded due to inadequate segmentation. The final study group comprised 88 nodules in 24 patients. 59 nodules were located in the upper or middle lobes and 29 were located in the lower lobes. Median (range) nodule diameter was 7mm (3mm – 25mm). Median (range) inspiratory nodule volume was 110mm3 (17mm3-4100mm3).Median (range) expiratory nodule volume was 116.5mm3 (18mm3-4061mm3). Median (range) inspiratory lung volume was 8372 ml (4960 – 10406 ml), and all patients achieved a reduction in lung volume on the expiratory scans, with a median (range) percentage reduction lung volume on expiratory scans of 25.3% (10.1 - 38.9%). Median (range) overall extent of emphysema was 36% (7.4% - 57.1%). On per nodule analysis, 59 of 88 nodules (67%) showed an increase in nodule volume at expiration (Figure 2). Mean difference in nodule volume between expiration and inspiration was + 7.5% (CI -24.1, 39.1%) (Figure 3). There was no difference in the mean nodule volume change between upper/middle lobe nodules (+7.2%) versus lower lobe nodules (8.2%) (p=0.8).Nodule size, percentage reduction in lung volume at expiration, and local emphysema extent had no relationship with lung nodule volume variability on linear regression. Median (range) local emphysema extent was 17.0% (0 - 90.9%). Interobserver agreement for local emphysema extent was good (interclass correlation co-efficient for absolute local emphysema extent 0.89, and weighted kappa for local emphysema severity grouping 0.87). DiscussionKnowledge of the impact of respiratory level on pulmonary nodule volumetry reproducibility is essential when assessing for true growth (and, thus, malignant potential) of pulmonary nodules on follow-up scans performed at different stages in the respiratory cycle.We hypothesized that with greater inspiration, the reduction in lung density surrounding lung nodules would cause better demarcation between nodule and lung, and hence produce smaller nodule volumes compared to expiratory scans. While we observed that the majority (67%) of nodules demonstrated an increase in volume at expiration, some nodules also reduced in size, and the overall average increase was small (+7.5%). Furthermore, we found no relationship between percentage change in lung volume at expiration and nodule volumetry variability.While there was a small number of nodules where variability was >40%, our results suggest that degree of inspiration may not be a hugely important factor in influencing nodule volumetry, especially when one considers that the magnitude of the changes that we observed is likely to be less substantial in clinical practice. Normally, sequential CTs will likely have been acquired using similar breathing instructions, with comparatively smaller changes in lung volumes. In fact, Gietema et al investigated the effects of inspiratory effort on nodule volume reproducibility by comparing measurements obtained on CT scans repeated on patients on the same day with identical breathing instructions (in contrast to our study of intentionally different levels of respiration). They concluded that the precision of nodule volumetry was weakly related to inspiratory effort (r = - 0.20; P < 0.047)ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1148/radiol.2452061054", "ISBN" : "10.1148/radiol.2452061054", "ISSN" : "0033-8419", "PMID" : "17923508", "abstract" : "PURPOSE: To prospectively assess the precision of semiautomated volume measurements of pulmonary nodules at low-dose multi-detector row computed tomography (CT) and to investigate the influence of nodule size, segmentation algorithm, and inspiration level. MATERIALS AND METHODS: This study had institutional review board approval; written informed consent was obtained from all patients. Between June 2004 and March 2005, 20 patients (15 men, five women; age range, 40-84 years; mean age, 57 years) referred for chest CT for known lung metastases underwent two additional low-dose chest CT examinations without contrast material (collimation, 16 x 0.75 mm). Between these examinations, patients got off and on the table to simulate the conditions for a follow-up examination. Noncalcified solid pulmonary nodules between 15 and 500 mm(3) that did not abut vessel or pleura were measured in both studies by using widely applied commercial semiautomated software. Interscan variability was established with the Bland and Altman approach. The impact of nodule shape (spherical or nonspherical) on measurement variability was assessed by using one-way analysis of variance, while the contributions of mean nodule volume and change in lung volume were investigated with univariate linear regression for completely (group A) and incompletely (group B) segmented nodules. RESULTS: Two hundred eighteen eligible nodules (volume range, 16.4-472.7 mm(3); 106 spherical, 112 nonspherical) were evaluated. The 95% confidence interval for difference in measured volumes was -21.2%, 23.8% (mean difference, 1.3%). The precision of nodule segmentation was highly dependent on nodule shape (P < .001) and was weakly related to inspiration level for completely segmented nodules (r = -0.20; P < .047), while mean nodule volume did not show any effect (P = .15 and P = .81 for group A and B nodules, respectively). CONCLUSION: Variation of semiautomated volume measurements of pulmonary nodules can be substantial. Segmentation represents the most important factor contributing to measurement variability, while change in inspiration level has only a weak effect for completely segmented nodules.", "author" : [ { "dropping-particle" : "", "family" : "Gietema", "given" : "Hester a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schaefer-Prokop", "given" : "Cornelia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mali", "given" : "Willem P T M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groenewegen", "given" : "Gerard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokop", "given" : "Mathias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Radiology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "888-894", "title" : "Pulmonary nodules: Interscan variability of semiautomated volume measurements with multisection CT-- influence of inspiration level, nodule size, and segmentation performance.", "type" : "article-journal", "volume" : "245" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[12]", "plainTextFormattedCitation" : "[12]", "previouslyFormattedCitation" : "[12]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[12]. The unpredictable impact of respiratory level we observed is also concordant with the findings of a previous study by Petkovska et al, who compared nodule volumes on CT performed at total lung capacity and then at residual volume. In their study of 75 nodules, nodule volume (and diameter) varied non-uniformly from total lung capacity to residual volume, with some nodules decreasing in size, while others increasedADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.acra.2007.01.008", "ISSN" : "1076-6332 (Print)", "PMID" : "17368218", "abstract" : "RATIONALE AND OBJECTIVES: We sought to determine how measures of nodule diameter and volume on computed tomography (CT) vary with changes in inspiratory level. MATERIALS AND METHODS: CT scans were performed with inspiration suspended at total lung capacity (TLC) and then at residual volume (RV) in 41 subjects, in whom 75 indeterminate lung nodules were detected. A fully automated contouring program was used to segment the lungs; followed by segmentation of all nodules and the corresponding lobe using semiautomated contouring in both TLC and RV scans. The percent changes in lung and lobar volumes between TLC and RV were correlated with percent changes in nodule diameters and volumes. RESULTS: Both nodule diameter and volume varied nonuniformly from TLC to RV-some nodules decreased in size, while others increased. There was a 16.8% mean change in absolute volume across all nodules. Stratified by size, the mean value of the absolute percent volume changes for nodules > or =5 mm and <5 mm were not significantly different (P = .26). Stratified by maximum attenuation, the mean value of the absolute percent volume changes between the TLC and RV series for noncalcified (17.7%, SD = 13.1) and completely calcified nodules (8.6% SD = 5.7) were significantly different (P < .05). CONCLUSION: Significant differences in nodule size were measured between TLC and RV scans. This has important implications for standardizing acquisition protocols in any setting where size and, more important, size change are being used for purposes of lung cancer staging, nodule characterization, or treatment response assessment.", "author" : [ { "dropping-particle" : "", "family" : "Petkovska", "given" : "Iva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brown", "given" : "Matthew S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Goldin", "given" : "Jonathan G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Hyun J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McNitt-Gray", "given" : "Michael F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abtin", "given" : "Fereidoun G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ghurabi", "given" : "Raffi J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aberle", "given" : "Denise R", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Academic radiology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2007", "4" ] ] }, "language" : "eng", "page" : "476-485", "publisher-place" : "United States", "title" : "The effect of lung volume on nodule size on CT.", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[11]", "plainTextFormattedCitation" : "[11]", "previouslyFormattedCitation" : "[11]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[11]. Our results also need to be considered alongside the fact that there is inherent variability in nodule size estimation using volumetry, regardless of breathing effort; with previous studies demonstrating inter-scan variability in nodule volume in the order of +/- 20%ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1148/radiol.2312030241", "ISBN" : "2312030241", "ISSN" : "0033-8419", "PMID" : "15128991", "abstract" : "PURPOSE: To evaluate software designed to calculate pulmonary nodule volume in three dimensions. MATERIALS AND METHODS: Fifty-four solid noncalcified pulmonary nodules measuring 5-18 mm in diameter were studied with computed tomographic (CT) volumetric software. Baseline CT examinations were performed for various indications by using four-detector row multisection CT units, 1.25- or 2.50-mm sections, and a standard reconstruction algorithm. The percentage of successful nodule segmentations, as well as intraobserver variability, interreader agreement, and global repeatability of calculated volumes, was determined on the basis of consecutive measurements performed three times by three different radiologists by using the Bland and Altman method. The software was used to calculate the doubling time of 22 nodules for which a final diagnosis and comparable CT scans were available. RESULTS: Fifty-two (96%) of the 54 nodules were successfully segmented, allowing their volume to be calculated. Repeatability was high: There was no variation in the nine measurements of 35 (67%) of the 52 nodules. The coefficient of variation for the remaining 17 nodules (33%) was 2.26%. Bland and Altman 95% limits of acceptability, calculated on the basis of log-transformed data, yielded a maximum software measurement error of 6.38% of the previous volume measurement. Doubling time ranged from 4 to 188 years for the 13 benign nodules and from 37 to 216 days for the nine malignant nodules. CONCLUSION: Software volumetric analysis yielded repeatable estimates for 96% of the nodules examined. All software-calculated doubling times were in keeping with the benign or malignant nature of the nodules.", "author" : [ { "dropping-particle" : "", "family" : "Revel", "given" : "Marie-Pierre", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lefort", "given" : "Catherine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bissery", "given" : "Alvine", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bienvenu", "given" : "Marie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Aycard", "given" : "Laetitia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chatellier", "given" : "Gilles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Frija", "given" : "Guy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Radiology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "459-466", "title" : "Pulmonary nodules: preliminary experience with three-dimensional evaluation.", "type" : "article-journal", "volume" : "231" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s00330-008-1229-x", "ISSN" : "09387994", "PMID" : "19018537", "abstract" : "We compared interexamination variability of CT lung nodule volumetry with six currently available semi-automated software packages to determine the minimum change needed to detect the growth of solid lung nodules. We had ethics committee approval. To simulate a follow-up examination with zero growth, we performed two low-dose unenhanced CT scans in 20 patients referred for pulmonary metastases. Between examinations, patients got off and on the table. Volumes of all pulmonary nodules were determined on both examinations using six nodule evaluation software packages. Variability (upper limit of the 95% confidence interval of the Bland-Altman plot) was calculated for nodules for which segmentation was visually rated as adequate. We evaluated 214 nodules (mean diameter 10.9 mm, range 3.3 mm-30.0 mm). Software packages provided adequate segmentation in 71% to 86% of nodules (p < 0.001). In case of adequate segmentation, variability in volumetry between scans ranged from 16.4% to 22.3% for the various software packages. Variability with five to six software packages was significantly less for nodules >or=8 mm in diameter (range 12.9%-17.1%) than for nodules <8 mm (range 18.5%-25.6%). Segmented volumes of each package were compared to each of the other packages. Systematic volume differences were detected in 11/15 comparisons. This hampers comparison of nodule volumes between software packages.", "author" : [ { "dropping-particle" : "", "family" : "Hoop", "given" : "Bartjan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gietema", "given" : "Hester", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ginneken", "given" : "Bram", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zanen", "given" : "Pieter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groenewegen", "given" : "Gerard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokop", "given" : "Mathias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Radiology", "id" : "ITEM-2", "issue" : "4", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "800-808", "title" : "A comparison of six software packages for evaluation of solid lung nodules using semi-automated volumetry: What is the minimum increase in size to detect growth in repeated CT examinations", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] }, { "id" : "ITEM-3", "itemData" : { "DOI" : "10.1148/radiol.2452061054", "ISBN" : "10.1148/radiol.2452061054", "ISSN" : "0033-8419", "PMID" : "17923508", "abstract" : "PURPOSE: To prospectively assess the precision of semiautomated volume measurements of pulmonary nodules at low-dose multi-detector row computed tomography (CT) and to investigate the influence of nodule size, segmentation algorithm, and inspiration level. MATERIALS AND METHODS: This study had institutional review board approval; written informed consent was obtained from all patients. Between June 2004 and March 2005, 20 patients (15 men, five women; age range, 40-84 years; mean age, 57 years) referred for chest CT for known lung metastases underwent two additional low-dose chest CT examinations without contrast material (collimation, 16 x 0.75 mm). Between these examinations, patients got off and on the table to simulate the conditions for a follow-up examination. Noncalcified solid pulmonary nodules between 15 and 500 mm(3) that did not abut vessel or pleura were measured in both studies by using widely applied commercial semiautomated software. Interscan variability was established with the Bland and Altman approach. The impact of nodule shape (spherical or nonspherical) on measurement variability was assessed by using one-way analysis of variance, while the contributions of mean nodule volume and change in lung volume were investigated with univariate linear regression for completely (group A) and incompletely (group B) segmented nodules. RESULTS: Two hundred eighteen eligible nodules (volume range, 16.4-472.7 mm(3); 106 spherical, 112 nonspherical) were evaluated. The 95% confidence interval for difference in measured volumes was -21.2%, 23.8% (mean difference, 1.3%). The precision of nodule segmentation was highly dependent on nodule shape (P < .001) and was weakly related to inspiration level for completely segmented nodules (r = -0.20; P < .047), while mean nodule volume did not show any effect (P = .15 and P = .81 for group A and B nodules, respectively). CONCLUSION: Variation of semiautomated volume measurements of pulmonary nodules can be substantial. Segmentation represents the most important factor contributing to measurement variability, while change in inspiration level has only a weak effect for completely segmented nodules.", "author" : [ { "dropping-particle" : "", "family" : "Gietema", "given" : "Hester a", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schaefer-Prokop", "given" : "Cornelia M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mali", "given" : "Willem P T M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groenewegen", "given" : "Gerard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokop", "given" : "Mathias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Radiology", "id" : "ITEM-3", "issue" : "3", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "888-894", "title" : "Pulmonary nodules: Interscan variability of semiautomated volume measurements with multisection CT-- influence of inspiration level, nodule size, and segmentation performance.", "type" : "article-journal", "volume" : "245" }, "uris" : [ "" ] }, { "id" : "ITEM-4", "itemData" : { "DOI" : "10.1007/s00330-003-2132-0", "ISBN" : "0938-7994", "ISSN" : "09387994", "PMID" : "14615902", "abstract" : "The aim of this study was to assess the in vivo measurement precision of a software tool for volumetric analysis of pulmonary nodules from two consecutive low-dose multi-row detector CT scans. A total of 151 pulmonary nodules (diameter 2.2-20.5 mm, mean diameter 7.4+/-4.5 mm) in ten subjects with pulmonary metastases were examined with low-dose four-detector-row CT (120 kVp, 20 mAs (effective), collimation 4x1 mm, normalized pitch 1.75, slice thickness 1.25 mm, reconstruction increment 0.8 mm; Somatom VolumeZoom, Siemens). Two consecutive low-dose scans covering the whole lung were performed within 10 min. Nodule volume was determined for all pulmonary nodules visually detected in both scans using the volumetry tool included in the Siemens LungCare software. The 95% limits of agreement between nodule volume measurements on different scans were calculated using the Bland and Altman method for assessing measurement agreement. Intra- and interobserver agreement of volume measurement were determined using repetitive measurements of 50 randomly selected nodules at the same scan by the same and different observers. Taking into account all 151 nodules, 95% limits of agreement were -20.4 to 21.9% (standard error 1.5%); they were -19.3 to 20.4% (standard error 1.7%) for 105 nodules <10 mm. Limits of agreement were -3.9 to 5.7% for intraobserver and -5.5 to 6.6% for interobserver agreement. Precision of in vivo volumetric analysis of nodules with an automatic volumetry software tool was sufficiently high to allow for detection of clinically relevant growth in small pulmonary nodules.", "author" : [ { "dropping-particle" : "", "family" : "Wormanns", "given" : "Dag", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kohl", "given" : "Gerhard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klotz", "given" : "Ernst", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Marheine", "given" : "Anke", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Beyer", "given" : "Florian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heindel", "given" : "Walter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Diederich", "given" : "Stefan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Radiology", "id" : "ITEM-4", "issue" : "1", "issued" : { "date-parts" : [ [ "2004" ] ] }, "page" : "86-92", "title" : "Volumetric measurements of pulmonary nodules at multi-row detector CT: In vivo reproducibility", "type" : "article-journal", "volume" : "14" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[5, 12, 15, 16]", "plainTextFormattedCitation" : "[5, 12, 15, 16]", "previouslyFormattedCitation" : "[5, 12, 15, 16]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[12, 15, 16].It could be anticipated that local emphysema would improve nodule volumetry reproducibility by reducing adjacent lung density, thereby improving nodule edge crispness and segmentation. However, we found no relationship between local emphysema extent and lung nodule volume variability. This result contrasts with a study by Goo et al which found a statistically significant correlation between inspiratory and expiratory nodule volumes and what they referred to as ‘regional emphysema’ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "1229-6929", "PMID" : "17143027", "abstract" : "OBJECTIVE: To evaluate how changes in lung volume affect volumetric measurements of lung nodules using a multi-detector row CT. MATERIALS AND METHODS: Ten subjects with asthma or chronic bronchitis who had one or more lung nodules were included. For each subject, two sets of CT images were obtained at inspiration and at expiration. A total of 33 nodules (23 nodules > or =3 mm) were identified and their volume measured using a semiautomatic volume measurement program. Differences between nodule volume on inspiration and expiration were compared using the paired t-test. Percent differences, between on inspiration and expiration, in nodule attenuation, total lung volume, whole lung attenuation, and regional lung attenuation, were computed and compared with percent difference in nodule volume determined by linear correlation analysis. RESULTS: The difference in nodule volume observed between inspiration and expiration was significant (p < 0.01); the mean percent difference in lung nodule volume was 23.1% for all nodules and for nodules > or =3 mm. The volume of nodules was measured to be larger on expiration CT than on inspiration CT (28 out of 33 nodules; 19 out of 23 nodules > or =3 mm). A statistically significant correlation was found between the percent difference of lung nodule volume and lung volume or regional lung attenuation (p < 0.05) for nodules > or =3 mm. CONCLUSION: Volumetric measurements of pulmonary nodules were significantly affected by changes in lung volume. The variability in this respiration-related measurement should be considered to determine whether growth has occurred in a lung nodule.", "author" : [ { "dropping-particle" : "", "family" : "Goo", "given" : "Jin Mo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kim", "given" : "Kwang Gi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gierada", "given" : "David S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Castro", "given" : "Mario", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bae", "given" : "Kyongtae T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Korean journal of radiology : official journal of the Korean Radiological Society", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "243-248", "title" : "Volumetric measurements of lung nodules with multi-detector row CT: effect of changes in lung volume.", "type" : "article-journal", "volume" : "7" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[10]", "plainTextFormattedCitation" : "[10]", "previouslyFormattedCitation" : "[10]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[10]. It is unclear whether this difference in findings relates to real variation on the impact of emphysema between the two studies or is due to differences in technique of emphysema measurement. We used a novel method of measuring local emphysema extent by analysing a segmentation region of interest immediately circumferential to each nodule; by contrast, Goo et al measured ‘regional emphysema’ in a region of interest adjacent to the pulmonary nodule, arguably analysing lung which would not directly impact on nodule segmentation. A limitation of our study is that the results are only valid for the software we used. In addition, we limited analysis to only include solid nodules, excluding subsolid nodules which are known to encompass their own technical challenges with regards to nodule segmentation. Also, although we hypothesize that expiration would tend to increase nodule volumes due to an increase in surrounding lung density, we did not specifically evaluate this relationship. However, by evaluating dedicated CTs performed at inspiration and expiration, our data provides additional evidence to suggest that effects of respiratory level on nodule reproducibility remain relatively inconsequential compared to those of scan acquisition, reconstruction and software factorsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00330-008-1229-x", "ISSN" : "09387994", "PMID" : "19018537", "abstract" : "We compared interexamination variability of CT lung nodule volumetry with six currently available semi-automated software packages to determine the minimum change needed to detect the growth of solid lung nodules. We had ethics committee approval. To simulate a follow-up examination with zero growth, we performed two low-dose unenhanced CT scans in 20 patients referred for pulmonary metastases. Between examinations, patients got off and on the table. Volumes of all pulmonary nodules were determined on both examinations using six nodule evaluation software packages. Variability (upper limit of the 95% confidence interval of the Bland-Altman plot) was calculated for nodules for which segmentation was visually rated as adequate. We evaluated 214 nodules (mean diameter 10.9 mm, range 3.3 mm-30.0 mm). Software packages provided adequate segmentation in 71% to 86% of nodules (p < 0.001). In case of adequate segmentation, variability in volumetry between scans ranged from 16.4% to 22.3% for the various software packages. Variability with five to six software packages was significantly less for nodules >or=8 mm in diameter (range 12.9%-17.1%) than for nodules <8 mm (range 18.5%-25.6%). Segmented volumes of each package were compared to each of the other packages. Systematic volume differences were detected in 11/15 comparisons. This hampers comparison of nodule volumes between software packages.", "author" : [ { "dropping-particle" : "", "family" : "Hoop", "given" : "Bartjan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gietema", "given" : "Hester", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ginneken", "given" : "Bram", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zanen", "given" : "Pieter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Groenewegen", "given" : "Gerard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokop", "given" : "Mathias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Radiology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2009" ] ] }, "page" : "800-808", "title" : "A comparison of six software packages for evaluation of solid lung nodules using semi-automated volumetry: What is the minimum increase in size to detect growth in repeated CT examinations", "type" : "article-journal", "volume" : "19" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1007/s00330-009-1634-9", "ISSN" : "09387994", "PMID" : "19921204", "abstract" : "OBJECTIVE: To assess volumetric measurement variability in pulmonary nodules detected at low-dose chest CT with three reconstruction settings. METHODS: The volume of 200 solid pulmonary nodules was measured three times using commercially available semi-automated software of low-dose chest CT data-sets reconstructed with 1 mm section thickness and a soft kernel (A), 2 mm and a soft kernel (B), and 2 mm and a sharp kernel (C), respectively. Repeatability coefficients of the three measurements within each setting were calculated by the Bland and Altman method. A three-level model was applied to test the impact of reconstruction setting on the measured volume. RESULTS: The repeatability coefficients were 8.9, 22.5 and 37.5% for settings A, B and C. Three-level analysis showed that settings A and C yielded a 1.29 times higher estimate of nodule volume compared with setting B (P = 0.03). The significant interaction among setting, nodule location and morphology demonstrated that the effect of the reconstruction setting was different for different types of nodules. Low-dose CT reconstructed with 1 mm section thickness and a soft kernel provided the most repeatable volume measurement. CONCLUSION: A wide, nodule-type-dependent range of agreement between volume measurements with different reconstruction settings suggests strict consistency is required for serial CT studies.", "author" : [ { "dropping-particle" : "", "family" : "Wang", "given" : "Ying", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bock", "given" : "Geertruida H.", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Klaveren", "given" : "Rob J.", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ooyen", "given" : "Peter", "non-dropping-particle" : "Van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tukker", "given" : "Wim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zhao", "given" : "Yingru", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Dorrius", "given" : "Monique D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Proen\u00e7a", "given" : "Rozemarijn Vliegenthart", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Post", "given" : "Wendy J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oudkerk", "given" : "Matthijs", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Radiology", "id" : "ITEM-2", "issue" : "5", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "1180-1187", "title" : "Volumetric measurement of pulmonary nodules at low-dose chest CT: Effect of reconstruction setting on measurement variability", "type" : "article-journal", "volume" : "20" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[15, 17]", "plainTextFormattedCitation" : "[15, 17]", "previouslyFormattedCitation" : "[15, 17]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[15, 17]. Indeed, our findings are likely to be a conservative representation of the effects of respiration on nodule volumetry reproducibility compared to daily clinical practice where differences in patients’ response to identical breathing instructions on consecutive scans would normally be less pronounced. ConclusionRespiratory effort has a modest but unpredictable effect on pulmonary nodule volumetry measurements, of doubtful clinical significance compared to inherent interscan variability. Local emphysema extent showed no effect on inspiratory and expiratory variability in this study.ReferencesADDIN Mendeley Bibliography CSL_BIBLIOGRAPHY 1. Saghir Z, Dirksen A, Ashraf H, et al. CT screening for lung cancer brings forward early disease. The randomised Danish Lung Cancer Screening Trial: status after five annual screening rounds with low-dose CT. Thorax 2012; 67:296–301.2. Horeweg N, Van Der Aalst CM, Vliegenthart R, et al. Volumetric computed tomography screening for lung cancer: Three rounds of the NELSON trial. Eur Respir J 2013; 42:1659–1667. 3. Field JK, Duffy SW, Baldwin DR, et al. UK Lung Cancer RCT Pilot Screening Trial: baseline findings from the screening arm provide evidence for the potential implementation of lung cancer screening. Thorax 2016; 71(2):161-70.4. Pastorino U, Rossi M, Rosato V, et al. Annual or biennial CT screening versus observation in heavy smokers: 5-year results of the MILD trial. Eur J Cancer Prev 2012; 21:308–315. 5. Revel M-P, Lefort C, Bissery A, et al. Pulmonary nodules: preliminary experience with three-dimensional evaluation. Radiology 2004; 231:459–466. 6. Revel M-P, Bissery A, Bienvenu M, et al. Are two-dimensional CT measurements of small noncalcified pulmonary nodules reliable? Radiology 2004; 231:453–458. 7. Callister MEJ, Baldwin DR, Akram AR, et al. British Thoracic Society guidelines for the investigation and management of pulmonary nodules: accredited by NICE. Thorax 2015; 70 :ii1–ii54. 8. Zhao B, Yankelevitz D, Reeves A, Henschke C Two-dimensional multi-criterion segmentation of pulmonary nodules on helical CT images. Med Phys 1999; 26:889–895. 9. Kim EY, Seo JB, Lee HJ, et al. Detailed analysis of the density change on chest CT of COPD using non-rigid registration of inspiration/expiration CT scans. Eur Radiol 2015; 25:541–549. 10. Goo JM, Kim KG, Gierada DS, et al. Volumetric measurements of lung nodules with multi-detector row CT: effect of changes in lung volume. Korean J Radiol 2006; 7:243–248.11. Petkovska I, Brown MS, Goldin JG, et al. The effect of lung volume on nodule size on CT. Acad Radiol 2007; 14:476–485. 12. Gietema HA, Schaefer-Prokop CM, Mali WP, et al. Pulmonary nodules: Interscan variability of semiautomated volume measurements with multisection CT-- influence of inspiration level, nodule size, and segmentation performance. Radiology 2007; 245:888–894.13. Hochhegger B Re: Respiratory Instructions for CT Examinations of the Lungs. Letters to the Editor, RadioGraphics 2009; 29:637–638.14. Wang Z, Gu S, Leader JK, et al. Optimal Threshold in CT Quantification of Emphysema. Eur Radiol 2013; 23:975–984.15. de Hoop B, Gietema H, van Ginneken B, et al. A comparison of six software packages for evaluation of solid lung nodules using semi-automated volumetry: What is the minimum increase in size to detect growth in repeated CT examinations. Eur Radiol 2009; 19:800–808.16. Wormanns D, Kohl G, Klotz E, et al. Volumetric measurements of pulmonary nodules at multi-row detector CT: In vivo reproducibility. Eur Radiol 2004; 14:86–92.17. Wang Y, De Bock GH, Van Klaveren RJ, et al. Volumetric measurement of pulmonary nodules at low-dose chest CT: Effect of reconstruction setting on measurement variability. Eur Radiol 2010; 20:1180–1187. Figure LegendsFigure 1Local emphysema extent was calculated by extending a segmentation area circumferentially around each nodule by approximately 1 cm, and using the “Hounsfield Unit Statistics” function within the Oncology application on SyngoVia Oncology package (Siemens, Erlangen, Germany) to calculate the percentage of surrounding lung with density of ≤ -950 HU.Figure 2(a) Right upper lobe nodule in patient with emphysema. Inspiratory CT (b) shows nodule volume as 0.261 mls,?which increased on expiratory?CT (c) to 0.329 mls.Figure 3Bland Altman plot display of inspiratory and expiratory pulmonary nodule volumes. ................
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