The Journal of Thoracic and Cardiovascular Surgery



Standard Operating

Procedures

Imaging Core

Bicuspid Aortic Valve Consortium

(BAVCon)

Version Date:

Approved by:

Table of Contents

1.0 Members of Imaging Core SOP Development Team: 3

2.0 Criteria for Complete Imaging 3

2.1 Inclusion Criteria 3

2.2 Exclusion Criteria 3

3.0 Core Principles of Data Acquisition: 3

4.0 General Principles of Imaging Methods 4

4.1 Assessment of the Bicuspid Aortic Valve 4

4.2 Assessment of the Ascending Aorta 7

4.3 Assessment of Aortic Valve Function 9

4.4 Assessment of Mitral Valve Prolapse 10

5.0 Procedures for Shipping Images to BAVCon Imaging Core 11

5.1 Image processing 11

5.2 Test cases 11

5.3 De-identification of images 11

5.4 Transfer of study images 11

5.5 Query process 12

6.0 Procedures for Receiving Study Media in the Core Laboratory. 14

6.1 Methods for QC Check of Collected Images 14

7.0 Specific Methods for Echocardiographic Imaging 15

7.1 Acquisition and measurement aortic valve peak and mean gradient 15

7.2 Aortic Valve Cusp Morphology 16

7.3 Mitral Valve Prolapse 18

8.0 Specific Methods for CT Imaging 19

8.1 Measurement of the Ascending Aorta 19

9.0 Specific Methods for MRI Imaging 24

1.0 Members of Imaging Core SOP Development Team:

BAvcon-ICORE

Arturo Evangelista (co-chair), Hector Michelena (co-chair), Alessandro Della Corte, Amelia Carro Hevia, Anna Booher, D Woodrow (Woody) Benson, Danny Muehlschlegel, Eduardo Bossone, Elena Ashikhmina, Gisela Teixid-Tur, Giuseppe Limongelli, Maurice Enriquez-Sarano, Patrick Mathieu, Philippe Pibarot, Robert Levine, Rodolfo Citro, Malenka Bissell, Federico Asch, Suhny Abarra, Nandan Anavekar

2.0 Criteria for Complete Imaging

2.1 Inclusion Criteria

1. Patients, identified retrospectively or prospectively, who have undergone echocardiogram (TTE or TEE), or gated MRI or gated CT demonstrating a definite BAV as determined by direct image viewing by one or more imaging core experts.

2. The size of the ascending aorta (root[sinuses], STJ and ascending tubular portion) has to be documented by an imaging study (TTE, TEE, CT or MRI)

3. The type of BAV (BAV phenotype) can be determined by imaging or direct observation (surgical or pathology).

4. A valvular degeneration score will be adjudicated to the aortic valve by imaging.

5. Severely calcified aortic valves may represent an imaging limitation, since it may be impossible to discern their bicuspid nature. In cases where the valve appears bicuspid, but because of the severe calcification, it is unclear whether there is acquired fusion of cusps vs. congenital fusion, the patient should be excluded. If an aortic valve, not previously determined to be bicuspid by imaging, is found to be congenitally fused by pathology, it can be included in the BAVcon registry.

2.2 Exclusion Criteria

1. Patients with “possible” BAV or unclear aortic valve cusp number that remain uncertain after independent review and consensus of 2 or more imaging core experts (not including the initial observer).

2. Patients with aortic valves that have 50%). Partial fusions < 50% or fusion just at the commissures will not be a definite BAV and thus excluded. Complete symmetry (equal cusp size) of the BAV will be described (yes or no, as assessed visually). A simple echocardiographic BAV degeneration scoring system evaluates 3 aspects: Cusp mobility, cusp calcification and cusp thickening. Figure 4 shows a type 1 BAV with raphe (arrow) and commissures at 10-4 o’clock. Figure 5 shows a type 2 BAV with raphe (arrow) and commissures at 1-7 o’clock. Figure 6 shows a basal SAX view obtained from MRI showing types 1 and 2 BAV with raphe. Figure 7 shows that pathologically, BAVs are mostly asymmetric, but there is a 5% or so that can be fully symmetric (equal sized cusps).

Figure 1. Schematic of the aortic valve short axis view. The right coronary cusp is anterior and positioned between the tricuspid valve and pulmonic valve. The left coronary cusp is posterior and related to the left atrium, while the non-coronary cusp is related to the interatrial septum (see figure 2)

[pic]

Figure 2. Clock visualization of the aortic valve for determination of the commissural positions.

[pic]

Figure 3. Cartoon demonstrates BAV phenotypes. Left-top shows a type 1 BAV (10 and 5 o’clock) with complete raphe, asymmetric (the non-fused cusp [non-coronary] is smaller than the fused anterior cusp). Top-middle shows a type 2 BAV (1 and 7 o’clock) with complete raphe and asymmetric (the non-fused cusp [left] is larger than the fused cusp). Top-right shows a type 3 BAV (2 and 8 o’clock, but could be 1 and 7 o’clock or 3 and 9 o’clock) with complete raphe, asymmetric (the non-fused cusp [right] is larger than the fused one).

Left-bottom shows a symmetric type 1 BAV with complete raphe. Bottom-middle shows a symmetrical type 1 BAV symmetric and without raphe (“true BAV”). Bottom-left shows a type 1 BAV with incomplete raphe, visually Asc Ao, Asc Ao > Root, and Asc Ao = Root (see datasheet). This determination is based on the actual measurements. Z-scores and BSA/height correction will be applied to measurements during analysis. An effaced STJ will be visually determined when the sinuses are in “straight” continuation with the sinuses without any angle between them (figure 9) or only a minimal angle can be identified (almost effaced=effaced). Effacement can be present (or not) for the 3 aortic phenotypes described. When looking at the sinuses of Valsalva in short axis, care must be taken to note by visual estimation, if one sinus is significantly larger/asymmetric in size compared to the others (see datasheet---Sinus asymmetry). For example, on figure 5, the left sinus outer length appears significantly larger than the rest. The presence of aortic coarctation will be recorded as assessed by 2-D echo [suprasternal view view of the descending thoracic aorta], color-flow Doppler, peak Doppler gradient and spectral Doppler morphology, or CT/MR as per current definitions.

Figure 8. Full vs. incomplete visualization of the ascending aorta. Note the ample/full visualization of the ascending aorta in A versus the limited one in B.

Modified from Schaefer HEART 2008.

A B

Figure 9. Aortic phenotypes

4.3 Assessment of Aortic Valve Function

Aortic stenosis will be assessed by mean Doppler gradient and peak trans-aortic velocity. If these variables are not present (retrospectively identified patients), then 2-D wide valvular opening will determine the absence of significant stenosis. If there are no Doppler measurements and there is aortic stenosis suspected by 2-D, then it will be classified as insignificant if it appears mild or mild-moderate, and significant if it appears moderate or more. At least another imager from the imaging-core should review these particular cases and if doubt remains, then more experts may review independently and reach a consensus.

Aortic regurgitation (AR) will be assessed by current ASE guidelines (Zoghbi et al. JASE 2003--US guidelines-- and Lancellotti et al. Eur J Echocardiogr 2010, parts 1 and 2—European guidelines--), using all available information. AR will be classified as none, mild, moderate or severe. If doubt remains, particularly for cases without semiquantitative or quantitative assessment (only visual assessment), then one or more core experts may independently review and then reach consensus. Aortic valve function will be also assessed by MRI. Phase contrast sequences with be obtained at the same slice position previously described (sinuses of Valsalva, sinotubular junction, ascending aorta, aortic arch and proximal descending aorta). Maximum velocity across the aortic valve and the regurgitant fraction will be determined. The information at all different levels will be used in order to determine the pulse wave velocity.

One mechanism of AR will be noted/recorded in the datasheet: aortic cusp prolapse. Figure 10 illustrates a common mechanism for AR in BAV patients: Prolapse of the conjoined cusp.

Figure 10. A common mechanism for aortic regurgitation in BAV.

First row is a TTE parasternal long axis view showing a type 1 BAV in systole (A) with doming of the conjoined cusp (anterior cusp, arrow), which prolapses in diastole (B, arrow) generating a very eccentric-posteriorly directed jet towards the mitral valve (C, arrows).

The second row is exactly the same but from a mid-esophageal TEE view at 130 degrees. Note the anterior cusp prolapse (A, arrows) with resulting posteriorly directed jet (B, arrow) towards the mitral valve.

4.4 Assessment of Mitral Valve Prolapse

The presence of mitral valve prolapse will be assessed by current recommendations (>= 2mm posterior displacement beyond the mitral annular plane), on parasternal long axis. A representative tomographic cut will be obtained by MRI if no echo available. Mitral regurgitation will be assessed by current ASE guidelines (Zoghbi et al. JASE 2003--US guidelines-- and Lancellotti et al. Eur J Echocardiogr 2010, parts 1 and 2—European guidelines--). If doubt remains, particularly for cases without semi-quantitative or quantitative assessment (only visual assessment), then one or more core experts may independently review and then reach consensus.

5.0 Procedures for Shipping Images to BAVCon Imaging Core

The purpose of this subheading is to describe the processes and requirement for the management of image data transfer from the BAVCon Clinical Centers (BCCs) to the Imaging Core.

5.1 Image processing

Each BCC is required to copy de-identified study images to a CD or DVD DICOM is the preferred file type but .avi files will also be accepted via email to the imaging core members.

5.2 Test cases

• Prior to initiating full-scale implementation at the BCC, each BCC must send one de-identified test case sample of images to the ICORE. This test case should contain parasternal long and short clips showing the diagnosis of BAV, as well as parasternal color-flow Doppler, and still images of the aorta measurements.

• The CD/DVD must be labeled as a sample test case. The Imaging Core will test the study format compatibility with its workstations. This may be sent in mpeg or .avi files by email as well.

• If the study format is compatible, the site will be informed that the method used in the de-identification and the transfer of the study image is approved and the site must utilize this method for all the study images. This confirmation will be done by email to the site coordinator.

• In the event a site changes the method for copying or de-identification, a new test case should be submitted.

5.3 De-identification of images

• The BCC must de-identify all images, which includes removal of all subject information including such things as name, date of birth, medical record number.

• Images must be identified only by the BAVCon subject ID.

• The date of the procedure must remain visible in the images whenever possible.

5.4 Transfer of study images

• The site will use the approved method of copying study images to a CD or DVD as well as the method of de-identifying subject information.

• Only one study must be copied in one CD/DVD and each CD/DVD must be labeled with the subject ID, modality (Echo, CT, MRI) and date of procedure.

• One Image Transmittal Form (Exhibit 1) must be completed and shipped with each CD/DVD. The transmittal form has been provided to the sites by the BAVcon ICORE, which can be re-sent by email if needed.

•

Imaging Core Image Transmittal Form

(Version 1.0, 1/18/2013)

BAVCon Subject ID:

| | | | | | |

Complete one Transmittal Form for each study sent to the BAVCon Imaging Core. Only one study per CD/DVD is permitted.

1. Date of Image: ______ |______|__________ (MM/DD/YYYY)

2. Type of Image: a. Transthoracic echo

b. Transesophageal echo

b. CT

c. MRI

3. Age (at time of image) | | |

RECORD ONLY IF OBTAINED WITHIN 12 MONTHS OF DATE OF IMAGE (please record the closest possible to imaging date):

4. Height | | | | cm

5. Weight | | | | . |_ | kg

Comments:

Form completed by:

Name Date (MM/DD/YYYY)

6.0 Other Specific Methods for Echocardiographic Imaging

6.1 Acquisition and measurement aortic valve peak and mean gradient, and AVA by continuity equation

The aortic valve area will be calculated by the continuity equation using time-velocity integrals and not peak velocities (Figure 11). The aortic valve function is quantitatively assessed by evaluating continuous wave (CW) Doppler through the valve. This is best accomplished with a non-imaging CW transducer using multiple windows of interrogation, i.e apical, left supraclavicular, suprasternal, right supraclavicular and very importantly: Right parasternal (Figure 12)

The maximum aortic valve velocity must be recorded by aligning the CW beam as parallel as possible to the aortic outflow. The peak and mean gradients are measured by tracing the transaortic valve CW Doppler.

Figure 11. The diagram shows how to calculate the aortic valve area (AVA) by multiplying the square of the LV outfl ow tract (LVOT) diameter obtained in the parasternal long-axis view by 0.785 and then by the TVI calculated by integrating the area under the curve (black-white interface) of the LVOT pulsed-wave spectral Doppler on the apical three-chamber view. Th is is then divided by the TVI of the continuous spectral Doppler signal through the aortic valve. Care must be taken when placing the pulse-wave sample volume near the aortic valve to avoid the high velocity fl ow convergence laminar fl ow area that precedes the aortic valve. Th is would cause overestimation of the AVA (underestimation of the severity of stenosis). Th is is achieved by placing the sample volume 0.5 to 1 cm before the aortic valve

[pic]

Figure 12.

The shown scheme represents the different anatomic positions to sample

for the maximal TVI of the aortic valve. The angle between the systolic fl ow and the beam should

be less than 20° [37] in order to prevent severe underestimation of the aortic valve TVI, which is

one the most common errors in stenosis evaluation (underestimation of severity).

[pic]

6.2 Aortic Valve Cusp Morphology

• Valve calcification

o The valve is assessed for calcification primarily from the parasternal long axis and short axis views. However, due to differences in cardiac anatomy an integrated approach for assessment will require the use of any view and angulations provided to best see the valve leaflets.

o The leaflets are visualized from a zoomed image in which the valve is “opened” to the maximum extent possible.

o Calcification will be reported as follows:

Grading

□ No or minimal “speckles”

□ Mild: 1calcific nodule in 1 cusp

□ Moderate: ≥2 nodules (any cusp or both)

□ Severe: Diffuse calcification involving all leaflets

• Leaflet Mobility

o The leaflets are assessed for mobility primarily from the parasternal long axis and short axis views. However, due to differences in cardiac anatomy an integrated approach for assessment will require the use of any view and angulations provided that best demonstrates the valve leaflets.

o The leaflets are visualized from a zoomed image and the conduit view is

“opened” to the maximum extent possible.

Grading

o Normal- Normal leaflet motion

o Mildly decreased – Small amount of tethering of the cusp tip but full excursion of the cusp body, or mild decreased systolic excursion of both cusps

o Moderately decreased – One cusp noted to have significantly/severe reduced systolic excursion or moderate decreased systolic excursion of both cusps

o Severely decreased – Both cusps noted to have significantly/severe reduced systolic excursion, usually associated with significant stenosis.

• Leaflet Thickening

o Leaflet thickness is assessed primarily from the parasternal long axis and short axis views. However, due to differences in cardiac anatomy an integrated approach for assessment will require the use of any view and angulations provided that best demonstrate the valve leaflets.

Grading (subjective)

o None (0) – Normal thin cusps

o Mild (1) –.

o Moderate(2)

o Severe (3) –

7.0 Specific Methods for CT Imaging

The methods for measuring the aorta described below were adopted by consensus of the members of the BAVCon imaging subcommittee. In order to avoid significant motion artifact during the cardiac cycle which negatively impacts assessment of the ascending aorta, ECG gated examination is recommended without and with intravenous iodinated contrast. The without contrast images will be limited to the heart to assess for aortic valve and coronary calcification. The portion of the examination with intravenous iodinated contrast will allow, in addition to assessment of the thoracic aorta, an assessment of cardiac function through volumetric determination of end systolic, end diastolic chamber volumes and left and right ventricular ejection fraction as well as assessment of the coronary arteries. In the event that iodinated contrast is contraindicated, an ECG gated non contrast study may be performed to acquire aortic measurements with the caveat that assessment of non-calcific atherosclerotic plaque/thrombus will be hindered.

7.1 Measurement of the Ascending Aorta

The segments of the aorta are measured at its maximum and minimum diameter including any thrombus, true or false lumen and excluding any atherosclerosis. Diameter measurements will be obtained by acquiring an imaging plane that is axial to the aorta at the level of measurement (double oblique measurement technique), see figure. This will provide a measurement that is perpendicular to the longitudinal or flow axis of the aorta to correct for the variable geometry of the aorta.

Also measured is the total area of the whole vessel to include thrombus, true and false lumens but excluding atherosclerosis. The latter can only be performed with a contrast enhanced study.

The time point in the cardiac cycle with the least degree of motion artifact is selected and this will be the primary phase dataset used for analysis of the aorta and its branches and the pulmonary artery.

The linear measurements of the aorta are performed from the double oblique plane as described above and demonstrated in figure 13. The measurement is taken from inner edge to inner edge of the vessel in diastole. The maximum diameter is taken from the largest diameter and the minimum diameter is the biggest measurement perpendicular to the maximum. In any segment in which there is a variable dilatation within the same segment, the measurement is taken where the total aorta size is the largest in that segment level (i.e. most aneurysmal level). Figure 14 shows double-oblique measurement of the aortic root (Sinuses of Valsalva). Figures 15, 16 and 17 show actual CT measurements for all aortic segments.

The measurement is reported in millimeters.

Figure 13.

Top-left demonstrates a coronal multiplanar reformation. An imaging plane longitudinal to the aorta results in a subsequent image depicted in top-right through which another plane is aligned longitudinal to the aorta (green) and a plane orthogonal to the latter (red) is also prescribed. The resulting image (bottom) is produced which is a plane that is axial to the ascending aorta at the level of the pulmonary arterial bifurcation.

Double oblique plane

Figure 14. Double-oblique aortic root measurement.

Maximum diameter

Minimum diameter

Figure 15.

Ascending Ao (PA)

ST Junction

Aortic Valve Annulus

Sinus of Valsalva

Aortic Valve Annulus - This is at the level the aortic valve leaflets.

Sinus of Valsalva – This is the largest diameter between the annulus and the STJ.

ST Junction – This is where the aortic root meets the ascending aorta (inflection point).

Ascending Aorta (PA) – This at the level of the PA bifurcation (or 1-2 cm above the STJ)

Ascending Aorta (Largest) – This is the largest diameter between the STJ and the first neck vessel takeoff.

.

Transverse

Arch Isthmus

Proximal Ao Arch

Figure 16.

Proximal Ao arch – this is just proximal to takeoff of the first neck vessel. Transverse arch – This is between first and second neck vessels. Isthmus – This is measured within 1 cm distal to the last neck vessel.

Mid Desc Thoracic Ao

(PA)

Thoracoabdominal Aorta

Suprarenal abdominal aorta

Figure 17.

Mid – descending thoracic Ao (PA) – This is at the level of the PA bifurcation (same spot as the ascending aorta)

Thoracoabdominal Aorta – This is measured at the level of the diaphragm or 2 cm above the celiac artery.

Supra-renal abdominal aorta – Midway between the celiac and superior mesenteric arteries.

9.0 Specific Methods for MRI Imaging

The methods for measuring the aorta described below were adopted by consensus of the members of the BAVCon imaging subcommittee.

The MRI examination will comprise several series without and with intravenous gadolinium contrast. The specific sequences will include steady state free precession sequence for assessment of aortic root caliber and cardiac function, black blood imaging to assess aortic wall thickness and MRA to assess the remaining thoracic aortic measurements. Balanced steady state free precession techniques will generate white blood images in the absence of contrast and produce cine images which will be important in the measurement of the aortic root whose caliber can change during the cardiac cycle. An imaging plane that is axial to the plane of the aortic valve and through the aortic root will allow for assessment of the aortic valve anatomy and will also allow for accurate measurement of the sinuses of Valsalva in both systole and diastole.

Black blood imaging, using spin echo sequences is used to evaluate aortic anatomy and morphology including aortic wall thickness. For the thoracic aorta, contrast enhanced MR angiography is performed with ECG gating at the cost of increased acquisition time for the benefit of motion free images of the aortic root and ascending aorta. The latter is important as a double check of measurements of the aortic root reported from the steady state free precession sequences. The contrast enhanced MR angiogram is obtained as a 3-dimensional volumetric dataset which can be manipulated and viewed in several different imaging planes as described in the assessment of the thoracic aorta using computed tomography. Similarly, aortic measurements should be performed using the double oblique measurement technique which assures that the measurement is taken in a plane that is perpendicular to the flow axis of the aorta. Cine phase contrast imaging can be performed to assess gradients across a stenotic valve or to determine regurgitant volume in the setting of aortic valvular regurgitation and can serve to complement the findings on echocardiographic examination.

The segments of the aorta are measured at its maximum and minimum diameter including any intraluminal thrombus, true or false lumen and excluding any atherosclerosis. Also measured is the total area of the whole vessel to include thrombus, true and false lumens but excluding atherosclerosis.

The linear measurements of the aorta are performed from the double oblique plane of the vessel as described above. Gated gradient echo cine is the best technique for aortic root assessment. The measurement is taken from inner edge to inner edge of the vessel in diastole. The maximum diameter is taken from the largest diameter and the minimum diameter is the biggest measurement perpendicular to the maximum. In any segment in which there is a variable dilatation within the same segment, the measurements are taken where the total aorta size is the largest in that segment level (i.e. most aneurysmal level). The measurement is reported in millimeters.

In cases where 3D datasets (usually angiograms) are not available, 2D measures will be performed from the available oblique 2D projections of the aorta. This can be achieved using black blood imaging technique but requires significant operator dependance to obtain imaging planes that are perpendicular to the flow axis of the aorta at the levels required for measurement. In this setting the mid and distal ascending aorta, mid aortic arch, proximal and distal descending thoracic aorta will need to be identified as points that require measurement including linear as well as area measurements at those prespecified regions Usually only a single measure of diameter and no measure of area will be available from such datasets. Figure 18 demonstrates a double-oblique aortic root (Sinuses of Valsalva) measurement. Figure 19 illustrates measurements of the ascending aorta segments.

Figure 20 illustrates measurements of the ascending aorta segments.

Distensibility:

Acquire SSFP Cine perpendicular to ascending aorta at the level of the pulmonary artery (best to use 3D planning tool). Use the following parameter: 400-mm field of view, 8-mm slice thickness, no gap, 1 number of excitations, flip angle 45°, matrix 224x224, and reconstruction matrix 256x 256. Adjust the number of cardiac phases according to the heart rate to obtain a temporal resolution of approximately 10 seconds as described by Aquato et al (2011).Distensibility is calculated using the following formula:

Distensibility [1 / mmHg] = (max_area - min_area) / pulse_pressure x min_area (Jackson 2009)

Automated tools are available at the University of Oxford, UK.

Pulse wave velocity:

Acquire through-plane phase contrast velocity mapping images with a high temporal resolution (90 phases) perpendicular to the ascending and descending aorta at the level of the pulmonary artery as well as an oblique sagittal black blood (half-Fourier single-shot turbo spin-echo [HASTE] scan sequence) or SSFP cine image of the ascending aorta. Transit time between normalized flow velocity curves is estimated using the half-maximum of the linear fit on the systolic upslope. Automated tools are available at the University of Oxford, UK.

FINAL POINTS FOR DISCUSSION—INPUT APPRECIATED

1)      The study of the aortic arch should be assessed at the mid arch in order to be reproducible in all studies.

2)      We would consider to include the study of the proximal descending aorta at the level of the pulmonary artery.

5)      Although the study of the aortic distensibility by CMR could be controversial, we consider that it can be useful and interesting in these set of patients. So we can perform cine sequences at the level of the ascending aorta, aortic arch and proximal descending aorta. We could also perform phase contrast sequences at the same slice position in order to obtain the pulse wave velocity. We have experience in this setting in a multicenter study with Marfan patients and although we experienced some difficulties in the post-processing we got interesting results.

[pic]

Figure 18.

Maximum diameter

Double oblique plane

Minimum diameter

Figure 19. The segments measured in the ascending aorta as shown in the following images:

Ascending Ao

(PA)

ST Junction

Sinus of Valsalva

Aortic Valve Annulus

Aortic Valve Annulus – This is at the level the aortic valve leaflets.

Sinus of Valsalva – This is the largest diameter between the annulus and the STJ.

ST Junction – This is where the aortic root meets the ascending aorta (inflection point).

Ascending Aorta (PA) – This at the level of the PA bifurcation (or 1-2 cm above the STJ)

Ascending Aorta (Largest) – This is the largest diameter between the STJ and the first neck vessel takeoff.

Figure 20.

Transverse

Arch

Proximal Ao Arch

Proximal Ao arch – this is just proximal to takeoff of the first neck vessel.

Transverse arch – This is between first and second neck vessels.

Isthmus – This is measured within 1 cm distal to the last neck vessel

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