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Lawrence L. Wald, Ph.D. MGH Martinos Center for Biomedical Imaging Michael Jerosch-Herold, PhD

MRI-Based Assessment of Neovasculariation in Carotid Plaque – A Novel Risk Marker for Plaque Rupture. Lawrence L. Wald, Ph.D. MGH Martinos Center for Biomedical Imaging Michael Jerosch-Herold, PhD Brigham & Women’s Hospital. Novel Risk Predictors for Plaque Vulnerability.

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Lawrence L. Wald, Ph.D. MGH Martinos Center for Biomedical Imaging Michael Jerosch-Herold, PhD

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  1. MRI-Based Assessment of Neovasculariation in Carotid Plaque – A Novel Risk Marker for Plaque Rupture Lawrence L. Wald, Ph.D. MGH Martinos Center for Biomedical Imaging Michael Jerosch-Herold, PhD Brigham & Women’s Hospital

  2. Novel Risk Predictors for Plaque Vulnerability • Systemic Markers / Risk Factors • Blood lipids, C-reactive protein, fibrinogen • Plaque-specific markers • Hemodynamic predictors • E.g. wall shear stress • Plaque neovascularization

  3. Neovascularization of Carotid Plaque Neovascularization of the vessel wall appears to be a consistent featureof inflamation and atherosclerotic plaque development. Due to their potential to promote intra-plaque hemorrhage and subsequent cholesterol deposition and plaque growth, plaque microvessels are considered markers of plaque vulnerability.

  4. 3T Imaging of Carotid Plaque 3D T1W imaging of plaque morphology

  5. New 3.0 T Bilateral 8-Channel Carotid Array and Head-Holder for Reynold Carotid Study Head Holder MGH Design Wiggins/Wald Reference: Hinton-Yates et al., TMRI 2007 8- Coils = pair of four 4.8 cm loops Coil mounted on a frame with head-holder consists of two curved paddles

  6. Patient Characteristics

  7. MRI Protocol for Dynamic Contrast Enhancement • T1-weighted 3D fast gradient echo • TR/TE/flip angle: 4.3/2.3 ms/ 20° • 3 mm slices • In-plane resolution: 0.7 x 0.7 mm • Time per dynamic view: 14 s • With new 8-element neck phased array the time per dynamic view is reduced to 10 s.

  8. Image Analysis mm mm • Carotid bifurcation was used as landmark to match MRI, PET, and CEA specimens • MRI: High resolution T1 and T2 spin echo images were used to identify plaque and to match with the CEA specimen. • FDG PET: ROIs were drawn around the CCA and/or ICA at a slice location matching the MRI-defined plaque and CEA specimen levels, using the anatomic landmarks from the CT scan of the PET/CT study. • Quant FDG uptake: For each slice, the arterial Standardized Uptake Value was calculated as the mean pixel activity within the ROI using a standard approach • SUVLBM= tissue activity (Ci/mL) / injected activity (mCi) / LBM (kg) • The arterial SUV (was corrected for blood activity by normalizing it to the average blood SUV estimated from the jugular vein to produce a blood-corrected arterial SUV (arterial tissue-to-background ratio)

  9. SPACE sequence for plaque morphology Isotropic resolution of 0.6 mm

  10. FDG-PET Co-Registered to Carotid MRI

  11. Image Analysis and Determinatin of First Order Capillary Transfer Rate Constant Contrast-Enhancement in Carotid Wall

  12. Kinetic Modeling(Kety-Schmidt Model) Measured in vessel lumen Venous Outflow Arterial Input vb Vascular Permeability Tissue Extraction (Ktrans) ΔCt= vp*ΔCp+ KtransCp • Model Parameters Determined by Optimization • vp vascular volume • Ktrans First order blood-to-tissue transfer rate constant

  13. Plaque Edema on T2 SPACE and Ktrans 03630993-R

  14. High Ktrans in plaque at carotid bifurcation T2 SPACE Area under Signal Curve (2 min. post injection) Ktrans P-NCHLS

  15. Correlation Between FDG PET and MR Ktrans R=0.463 P=0.017

  16. Complex ICA Plaque ECA ICA lumen ICA plaque Dark-Blood T2-w SPACE Ktrans map of ICA wall and plaque Area under SI curve (AUC) (2 min. window) P-NCHLS-R

  17. Plaque Edema and Ktrans Ktrans - ICA SPACE (T2w) ICA 16549180-R

  18. Correspondence between regions with high SI on T2 SPACE and Ktrans map of ICA wall T2 SPACE Ktrans map T2 SPACE above carotid bifurcation P-BSHTT-left

  19. Association between Signal Intensity Level in Carotid Wall with T2 SPACE and Ktrans Perfusion Parameter

  20. Correlation of MRI Parametric Maps with Histology

  21. Macrophage Density by Ktrans Categories R=0.80 P=0.03

  22. Plans • 3 accepted abstracts for May 2010 ISMRM conference • “High Resolution 3D Carotid Plaque Perfusion Mapping and its Association with T2 Hyperintensity” • “3D Isotropic Non-contrast Approach for the Assessment of Carotid Arteries Stenosis at 3T” • “T1 Contrast in MPRAGE for Carotid Plaque Imaging” • Enrollment of more patients scheduled for endarterectomy for comparison with plaque pathology • Future sponsored studies

  23. Acknowledgements • Co-Investigators: Larry Wald (Co-PI), Raymond Kwong, Marcelo Di Carli • Support through Partners Radiology Research Award

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