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Aeha aha 2002 poster

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Aeha aha 2002 poster

  1. 1. Anatomical Basis for MRI Assessment of Human Atherosclerotic Disease: MRI Dimensions of Post-Mortem Carotid Artery Pairs from 38 Elderly Individuals W. Insull Jr., G. J. Adams, C. B. Bordelon Jr., J. D. Morrisett Baylor College of Medicine, Houston TX Contact Info: William Insull Jr., M.D. winsull@bcm.tmc.edu Joel D. Morrisett, Ph.D. morriset@bcm.tmc.edu
  2. 2. Abstract Carotid artery atherosclerosis is a significant cause of strokes and can be evaluated non-invasively by MRI. The purpose of this study was to determine by MRI and EBCT the anatomical pathology of atherosclerosis in elderly individuals most likely to have fullest expression of atherosclerosis. Pairs of carotid artery segments around the bifurcation were obtained from 38 individuals in the anatomical laboratory after pressure perfusion fixation. They were examined by high resolution MRI using a 1.5T clinical MR system equipped with a phased array coil and by clinical EBCT. We measured the location of the atherosclerotic plaque along the artery, the volumes of the artery wall and lumen, and estimated the plaque volume. The replicate variation for intra- and interscan volumes (coefficients of variation) measured the minimum variances for the clinical MRI scan procedure excluding patient-dependent sources of variance. Both MRI and EBCT showed close bilateral symmetry of lesions for dimensions and calcium content, respectively. Carotid plaques appeared to be single lesions with maximum development at the bifurcation diminishing progressively to terminate about 15 mm distal and proximal to the bifurcation. We identified the implications of these anatomical observations for the concepts of development of atherosclerosis in single carotid lesions and noted potential clinical applications.
  3. 3. Background • Carotid atherosclerosis provides a potentially fruitful site for the study of atherosclerosis development, diagnosis, and treatment. • The carotid artery bifurcation is highly susceptible to atherosclerosis. • The growth and development of carotid lesions is unlimited throughout all ages since lesion size is not restricted by the limits of anatomical geometry of the artery. • Advanced lesions of carotid atherosclerosis occur in populations with high prevalence of atherosclerosis, stages IV to VII by the AHA classification 1995. • All earlier stages of atherosclerotic lesions occur simultaneously with the most advanced lesions, generally distributed radially and sequentially directly adjacent to and contiguous to these most advanced lesions. • The microscopic pathological characteristics of carotid atherosclerosis are similar to atherosclerosis at other clinically significant arterial sites, coronary arteries, peripheral arteries and aorta. • Inter-individual variation in extent of carotid AS is broad within and among populations, similar to wide variance for coronary and aortic disease. • The symmetrical pairing of carotid arteries provides an opportunity to evaluate the variance of atherosclerosis lesions between similar sites within each individual. • Carotid arteries are readily accessible to non-invasive imaging by a variety of techniques, including B mode ultrasound, computed tomography and magnetic resonance imaging.
  4. 4. Purpose Sample Acquisition: • Cadaveric carotid arteries were used as the model. • Fifty perfusion-fixed carotid pairs were excised from human cadavers aged 74±13 (48-98) years. • Of the 50 sample pairs, 38 contained the entire plaque and were suitable for rigorous analysis. 3D Reconstruction of a Carotid Artery from multiple 3mm thick MRI slices. Cadaveric Carotid Artery Specimen To describe the anatomical, pathological, and dimensional characteristics of carotid atherosclerosis in elderly individuals using high resolution MRI 1.5T and EBCT.
  5. 5. Cadaveric Carotid Arteries Useful properties of the cadaveric carotid artery samples: a) Tissue was pressure perfusion fixed before excision, which preserves the tissue and maintains in vivo geometry. b) Most of the periadventitial tissue has been removed, which reduces specimen bulk while retaining essential anatomical features. CCA BIF ICA ECA Single Cadaveric Carotid Artery Sample The common carotid artery (CCA), bifurcation (BIF), external carotid artery (ECA), and internal carotid artery (ICA) are clearly seen.
  6. 6. Properties of Cadaveric Carotid Arteries Essential properties of the cadaveric carotid artery samples: • Contain all three layers of the arterial wall (intima, media, adventitia), and some perivascular soft tissue. • Contain a range of lesion types. • Give reproducible images over >1 year. • Provide stable reference for: • intra-laboratory standardization • inter-laboratory standardization for multicenter clinical trials Other useful attributes: • Enables comparison of left and right carotids from an individual. • Can be analyzed using independent techniques other than MRI (e.g. histology, µCT, FTIR spectroscopy).
  7. 7. Imaging Protocol Samples in EBCT Scanner Ex Vivo Imaging Apparatus 1.5T GE Clinical MRI Scanner An Imatron EBCT scanner and AccuImage software were used to obtain calcification scores for each sample. A 1.5T GE Horizon LX clinical MRI equipped with Pathway phased array coils was used to acquire PDW, T1W, and T2W images with an in-plane spatial resolution of 0.195 mm and a slice thickness of 3mm.
  8. 8. Carotid Artery Volume Quantitation using MRI Measurement Algorithm: • A semiautomatic active contour algorithm was used to define the boundaries of the lumen and the outer wall of the artery. • The generalized gradient vector field force was used as the external force for the active contour algorithm. • The area of each contour was measured and multiplied by the slice thickness to obtain the volume. T2W MRI Image Internal Lumen External Lumen Artery Wall 1. Initial Contours 2. Final Contours 3. Measurements
  9. 9. Plaque Volume Estimation and Assumptions Estimation: • Estimate normal wall thickness as the average minimum wall thickness within each branch of the carotid tree. • Estimate normal wall volume by sweeping a thickness contour around the outer wall. • Plaque Volume = Total Wall Volume – Normal Wall Volume. • Percent Stenosis = Plaque Volume / Estimated Normal Lumen. Assumptions: • A normal, non-diseased wall is represented by the wall with the minimal thickness. • Normal wall thickness remains constant around the artery wall. • Normal wall thickness remains the same within each branch of the carotid. Internal Lumen External Lumen Artery Wall 2. Measurements1. T2W MRI Image Normal Wall Plaque 3. Plaque Estimate
  10. 10. Comparison of Volumes within Artery Pairs Computation and Comparison of Aggregate Volumes: • For comparison purposes, slices were indexed by their distance from the bifurcation. • The bifurcation was defined as the first MRI slice in which both the internal and external lumen were visible as two separate orifices. • Aggregate volumes for nine contiguous slices bounding the bifurcation were computed for each sample. 1. Locate Bifurcation 2. Align Slices by Offset 3. Compute Volumes MRI of Left Carotid Artery MRI of Right Carotid Artery Slice 10 Slice 11 Offset 0 on Left Offset 0 on Right Left Aggregate Volume Right Aggregate Volume
  11. 11. Multiple Contrast Imaging PDW T1W T2W Contiguous 3mm thick MRI slices. I/E2 I/E1 Bifurc. C1 C2 • Tissues were imaged using multiple contrast weightings, including proton density, T1, and T2-weightings. • The different weightings provide differential contrast among principal tissue components (e.g. necrotic core, fibrous cap, calcification, thrombus) within the atherosclerotic plaque. • Cai et al. have demonstrated that it is possible to differentiate between different tissue types using multi-contrast MR imaging in vivo.
  12. 12. LuLu HH RCRC LiLi FCFC SSSS Correlation of Histology and MR Imaging • Cross-sectional MR images closely match histology slices.
  13. 13. Carotid Volume Distributions Slice volume averages were computed for slices at the same offset in the left and right carotid arteries for the 38 pairs. Average Left Slice Volumes at Offset 0 Sample 1 Offset 0 Left + Sample 2 Offset 0 Left Average Right Slice Volumes at Offset 0 Sample 1 Offset 0 Right + Sample 2 Offset 0 Right = =vs.
  14. 14. 0 20 40 60 80 100 120 140 160 C10 C8 C6 C4 C2 B I2/E2 I4/E4 I6/E6 Slice Volume(mm 3 ) Common Internal External Lumen Volume Distributions in the Left and Right Carotids Slice volume profiles measured using the semiautomated active contour algorithm. Distance between slices is 3mm. Dotted lines are left carotid volumes. Solid lines are right carotid volumes.
  15. 15. 0 50 100 150 200 250 300 350 400 C10 C8 C6 C4 C2 B I2/E2 I4/E4 I6/E6 Slice Volume(mm 3 ) Common Internal External Total Artery Volume Distributions in the Left and Right Carotids Slice volume profiles measured using the semiautomated active contour algorithm. Distance between slices is 3mm. Dotted lines are left carotid volumes. Solid lines are right carotid volumes.
  16. 16. 0 50 100 150 200 250 C10 C8 C6 C4 C2 B I2/E2 I4/E4 I6/E6 Slice Volume(mm 3 ) Common Internal External Total Wall Volume Distributions in the Left and Right Carotids Total wall slice volume profiles calculated as total artery volume minus lumen volume. Distance between slices is 3mm. Dotted lines are left carotid volumes. Solid lines are right carotid volumes.
  17. 17. 0 20 40 60 80 100 120 140 C10 C8 C6 C4 C2 B I2/E2 I4/E4 I6/E6 Slice Volume(mm 3 ) Common Internal External Normal Wall Volume Distributions in the Left and Right Carotids Slice volume profiles estimated using the automated plaque estimation algorithm. Distance between slices is 3mm. Dotted lines are left carotid volumes. Solid lines are right carotid volumes.
  18. 18. 0 10 20 30 40 50 60 70 80 C10 C8 C6 C4 C2 B I2/E2 I4/E4 I6/E6 Slice Volume(mm 3 ) Common Internal External Dotted lines are left carotid volumes. Solid lines are right carotid volumes. Plaque Volume Distributions in the Left and Right Carotids Slice volume profiles estimated using the automated plaque estimation algorithm. Distance between slices is 3mm. Plaque volume is concentrated near the bifurcation, with 80% of the plaque within 9mm of the bifurcation in the internal carotid, 12 mm within the external carotid, and 18mm in the common carotid.
  19. 19. 0% 5% 10% 15% 20% 25% 30% 35% 40% 45% 50% C10 C8 C6 C4 C2 B I2/E2 I4/E4 I6/E6 Slice Volume(mm 3 ) Common Internal (Circles) External (Triangles) Percent Stenosis Distributions in the Left and Right Carotids Slice volume profiles estimated using the automated plaque estimation algorithm. Distance between slices is 3mm. Percent stenosis was calculated by dividing the estimated plaque volume by the estimated original lumen. Dotted lines are left carotid volumes. Solid lines are right carotid volumes.
  20. 20. Wall Thickness Distributions • Wall thickness distributions were calculated for each MR slice in the carotid artery. • Averages for each branch were computed by taking the mean of the average wall thickness of each slice within that branch. • Maximums for each branch were computed by finding the largest maximum wall thickness for each slice within that branch. Maximum Wall Thickness
  21. 21. Scatter Plots of the Average and Max Wall Thickness in mm. of the Internal, External and Common Carotid Artery Branches from MRI 0 1 2 3 0 1 2 3 Left Internal RightInternal 0 1 2 3 0 1 2 3 Left External RightExternal 0 1 2 3 0 1 2 3 Left Common RightCommon r=0.63r=0.75r=0.48 0.0 2.5 5.0 7.5 10.0 0.0 2.5 5.0 7.5 10.0 Left Common RightCommon 0.0 2.5 5.0 7.5 0.0 2.5 5.0 7.5 Left Internal RightInternal 0.0 2.5 5.0 7.5 0.0 2.5 5.0 7.5 Left External RightExternal r=0.57r=0.23 r=0.52 Average Wall Thicknesses Maximum Wall Thicknesses
  22. 22. Scatter Plots of the Average Wall Thickness v. the Maximum Wall Thickness in mm. of the Internal, External and Common Carotid Artery Branches from MRI 0 1 2 3 0.0 2.5 5.0 7.5 Left Internal Avg LeftInternalMax 0 1 2 3 0.0 2.5 5.0 7.5 Right Internal Avg RightInternalMax 0 1 2 3 0 1 2 3 4 5 Left External Avg LeftExternalMax 0 1 2 3 0.0 2.5 5.0 7.5 Right External Avg RightExternalMax 0 1 2 3 0.0 2.5 5.0 7.5 10.0 Left Common Avg LeftCommonMax 0 1 2 3 0.0 2.5 5.0 7.5 10.0 Right Common Avg RightCommonMax r=0.73 r=0.85 r=0.74 r=0.71 r=0.79 r=0.53
  23. 23. Aggregate Volumes Statistics Aggregate volumes were computed for nine contiguous slices bounding the bifurcation for each sample in the 38 pairs. vs. Left Aggregate Volume Right Aggregate Volume
  24. 24. 0 500 1000 1500 2000 0 500 1000 1500 2000 Left Lumen RightLumen Scatter Plots of Carotid Artery Aggregate Volumes from MRI 0 1000 2000 3000 4000 0 1000 2000 3000 4000 5000 Left Total Artery RightTotalArtery 0 1000 2000 3000 0 1000 2000 3000 Left Total Wall RightTotalWall0 500 1000 1500 2000 0 500 1000 1500 2000 Left Normal Wall RightNormalWall 0 500 1000 1500 0 500 1000 1500 Left Plaque RightPlaque 0 25 50 75 0 25 50 75 Left Percent Stenosis RightPercentStenosis
  25. 25. Average Carotid Artery Aggregate Volumes from MRI 0 500 1000 1500 2000 2500 3000 3500 Left Lumen Volume Right Lumen Volume Left Total Artery Volume Right Total Artery Volume Left Total Wall Volume Right Total Wall Volume Left Normal Wall Volume Right Normal Wall Volume Left Plaque Volume Right Plaque Volume • Average volumes in mm3 for left and right carotid volumes from MRI. • None of the left v. right volumes were significantly different. • Error bars are standard deviations.
  26. 26. Scatter Plots of Carotid Artery Calcium Volume Scores from EBCT 0 500 1000 1500 2000 0 500 1000 1500 2000 Left Calcium Volume Score RightCalciumVolumeScore 0 1000 2000 3000 0 1000 2000 3000 Left Agatston Score RightAgatstonScore • Two separate scores were computed from the same images. • The Agatston Score is calculated based on calcification area times a scale factor. • The Volume Score uses the isotropic interpolation to calculate the volume of calcification. • The two calcification scores are highly correlated with one another (r=0.997). • The scores are not normally distributed within the population of individuals.
  27. 27. Average Carotid Artery Calcification Scores from EBCT Two separate scores were computed from the same images. The Agatston Score is calculated based on calcification area times a scale factor, whereas the Volume Score uses the isotropic interpolation to calculate the volume of calcification. Left and Right Carotid Artery EBCT Calcification Scores from 38 Sample Pairs Error Bars are Standard Deviations Agatston Score Volume Score -200 0 200 400 600 800 1000 Left Agatston Score Right Agatston Score Left Calcium Volume Score Right Calcium Volume Score
  28. 28. Left v. Right Carotid Volume (MRI) and Agatston Score (EBCT) Concordance Correlations • Lin’s concordance correlation coefficients of left and right carotid volumes from MR and left and right calcification scores from EBCT. • Lin’s concordance correlation coefficient measures the agreement between a pair of variables. • Error bars are 95% confidence intervals. 0.54 0.63 0.71 0.64 0.58 0.51 0.95 0.94 0.0 0.2 0.4 0.6 0.8 1.0 Lumen Volume Total Artery Volume Total Wall Volume Normal Wall Volume Plaque Volume Percent Stenosis Agatston Score Volume Score ConcordanceCorrelationCoefficient
  29. 29. Correlations between Agatston Score (EBCT) and Aggregate Volumes (MRI) Correlations of Agatston Score vs Aggregate Volumes (N=76) Error Bars are 95% Confidence Intervals -0.17 0.27 0.50 0.46 0.44 0.53 -0.60 -0.40 -0.20 0.00 0.20 0.40 0.60 0.80 1.00 Lumen Volume Total Artery Volume Total Wall Volume Normal Wall Volume Plaque Volume Percent Stenosis Aggregate Volume CorrelationCoefficient
  30. 30. Reproducibility Statistics • To test the reproducibility of MRI imaging of the models, two image sets, consisting of two full acquisitions (PDW, T1W, T2W) on four models, were acquired. • Between the two sets the holder was removed from the magnet, the coils were removed from the holder, and the temperature of the water bath was re- equilibrated. • Arterial volumes of each model were quantified using the semiautomated algorithm. • The reproducibility of the measured volumes from the different models is quantified using the coefficient of variation (mean±SD), which is expressed as a percentage. Lumen Total Wall Normal Wall Plaque Within Sets COV (N=8) 0.33±0.24 0.70±0.30 1.01±1.11 2.48±2.14 Between Sets COV (N=4) 2.19±2.00 2.63±1.75 3.96±2.16 4.47±1.56
  31. 31. Summary of Results The anatomical characteristics of the carotid plaques have been described by the average values of the study subjects: • Carotid plaque is a single continuous lesion extending from the common carotid into the internal and external branches, without evidence of discontinuities of structure that indicate multiple plaques at the carotid site. • Lesions are located at the region of the bifurcation, presumably in the area of the carotid bulb, within 15mm proximally and distally from the flow divider. Lesions’ longitudinal development within the artery wall appears to be equal along the common carotid and the internal and external branches. • Lesion bulk is greater in the internal carotid that in the internal carotid. Volumes within the external carotid are 30 to 50% smaller per slice. • The sum of the plaque volumes in the internal and external carotid in the slice most proximal to the bifurcation is equal to the plaque volume in the common carotid slice most proximal to the bifurcation. • The maximum volume of plaque is at the region of the bifurcation. This is probably the region with the most advanced plaque. • Proximal and distal to the region of maximal development, the volume per slice decreases rapidly in a curvilinear fashion.
  32. 32. Discussion of Results 1. Studying elderly patients has the inherent advantage of studying individuals with the fullest development of atherosclerosis due to prolonged exposure to all risk factors. The development of carotid atherosclerosis, raised lesions to the naked eye, is progressive with age and in high risk populations is a companied by increasing occurrence of complicated and calcified lesions. Solberg et al 2. The analysis of variance of MRI measurements of a single cadaveric carotid artery provides an estimate of the minimum variance achievable with the MRI scan procedure alone. This procedure excludes all sources of variance related to patients, as within scan movements, and interscan differences of positioning and movement. This provides as basis for systematic analysis of variance of MRI clinical scans that are essential for estimating sample sizes for studies of treatment effects on the dimensions of the plaque volume. 3. The comparison of pairs of carotids within individual patients shows the strong bilateral symmetry of the disease. This supports the use of analysis of a single artery as an estimate of the burden of atherosclerosis among similar arteries. It also starts to define the inter-arterial variance of atherosclerosis within an individual, the least difference as it occurs between bilaterally symmetrical arteries.
  33. 33. Discussion of Results The analysis provides measurements on the development of atherosclerosis within a single plaque. The results support the following statements: • The plaque region with the greatest volume, at the carotid bifurcation, probably has the plaques most advanced stage of development, and are probably the oldest region of the plaque. • The plaque regions with the smallest detectable volumes, at the proximal and distal edges of the plaque, probably have the earliest stage of development, and are the youngest region of the plaque. • Since plaques appear to grow centrifugally along radial vectors, similar young regions probably occur at the lateral edges of the plaque. • These observations support the concept of the plaques’ centrifugal growth and development along radii from the initial site. • Whether the grades of lesions described by the AHA classification are arranged along the radial vectors of growth requires further study.
  34. 34. Discussion of Results The analysis of the anatomical dimensions of carotid plaques from MRI images has substantial implications for clinical use of MRI: • Diagnosis of atherosclerosis by detection of arterial lesions. • Staging of the development of carotid atherosclerosis. Staging procedures require initially the quantitative measurements of the lesion location and the lesions’ physical dimensions. While plaques’ degree of surface involvement surface, and compositional heterogeneity have been used customarily for staging plaque development, the volume of the plaque can now be used to further define the stage of development. • Rationale for selection of therapy based on the characteristics of the plaque, it’s location, dimensions and composition. • Monitoring therapy developing criteria for significant therapeutic effect, as reduction in plaque volume. • Adjusting therapy if treatment effects are not satisfactory • Guidance to endarterectomy surgeon for dissection to excise lesions.
  35. 35. References and Acknowledgements References • Adams GJ, Simoni DM, Bordelon CB, et al. Stroke. 2002;33:2575- 2580. • Cai J-M, Hatsukami TS, Ferguson MS, et al. Circulation. 2002;106:1368-1373. • Karmonik C, Eldrige C, Vick GW, et al. Am J Cardiol. 2001;88:78E. • Solberg LA, McGarry PA, Moossy J, et al. Ann N Y Acad Sci. 1968;149:956-973. • Stary HC, Chandler AB, Dinsmore RE, et al. Circulation. 1995;92:1355-1374. • Zarins CK, Giddens DP, Bharadvaj BK, et al. Circ. Res. 1983;53:502- 514. Acknowledgements • Funding was provided by grants to Dr. Morrisett from the Welch Foundation (Q1325) and the National Heart, Lung and Blood Institute of the NIH (HL07812 and HL63090. • Gareth Adams was supported in part by a training fellowship from the Keck Center for Computational and Structural Biology of the Gulf Coast Consortia (NLM 5T5LM07093). • EBCT calcification scoring was performed by Darlene Simoni, RT.

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