MRI-Based Assessment of Neovasculariation in Carotid Plaque – A Novel Risk Marker

for Plaque RuptureLawrence L. Wald, Ph.D.

MGH Martinos Center for Biomedical Imaging

Michael Jerosch-Herold, PhDBrigham & Women’s Hospital

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

Neovascularization of Carotid PlaqueNeovascularization of Carotid Plaque

• Neovascularization of the vessel wall Neovascularization of the vessel wall appears to be a consistent featureappears to be a consistent feature of of inflamation and atherosclerotic plaque inflamation and atherosclerotic plaque developmentdevelopment. .

• Due to their potential to promote intra-Due to their potential to promote intra-plaque hemorrhage and subsequent plaque hemorrhage and subsequent cholesterol deposition and plaque growth, cholesterol deposition and plaque growth, plaque microvessels are considered plaque microvessels are considered markers of plaque vulnerabilitymarkers of plaque vulnerability..

3T Imaging of Carotid Plaque

3D T1W imaging of plaque morphology

New 3.0 T Bilateral 8-Channel Carotid Array and Head-Holder for Reynold Carotid Study

Coil mounted on a frame with head-holder consists of two curved paddles

MGH DesignWiggins/Wald

Reference: Hinton-Yates et al., TMRI 2007

8- Coils = pair of four 4.8 cm loops

Head Holder

Patient CharacteristicsPatient Characteristics

N=33N=33

AgeAge 71±971±9

MaleMale 16 (48%)16 (48%)

DiabetesDiabetes 11 (33%)11 (33%)

HypertensionHypertension 21 (64%)21 (64%)

SmokingSmoking 6 (18%)6 (18%)

History of CV diseaseHistory of CV disease 17 (52%)17 (52%)

Prior MIPrior MI 4 (12%)4 (12%)

TIA/StrokeTIA/Stroke 5 (15%)5 (15%)

SymptomaticSymptomatic 10 (30%)10 (30%)

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.

Image AnalysisImage Analysis

• Carotid bifurcation was used as landmark to match MRI, Carotid bifurcation was used as landmark to match MRI, PET, and CEA specimensPET, and CEA specimens

• MRIMRI: High resolution T1 and T2 spin echo images were : High resolution T1 and T2 spin echo images were used to identify plaque and to match with the CEA used to identify plaque and to match with the CEA specimen.specimen.

• FDG PETFDG PET: ROIs were drawn around the CCA and/or ICA : ROIs were drawn around the CCA and/or ICA at a slice location matching the MRI-defined plaque and at a slice location matching the MRI-defined plaque and CEA specimen levels, using the anatomic landmarks from CEA specimen levels, using the anatomic landmarks from the CT scan of the PET/CT study. the CT scan of the PET/CT study.

• Quant FDG uptakeQuant FDG uptake: For each slice, the arterial : For each slice, the arterial Standardized Uptake Value was calculated as the mean Standardized Uptake Value was calculated as the mean pixel activity within the ROI using a standard approachpixel activity within the ROI using a standard approach

– SUVSUVLBMLBM= tissue activity (= tissue activity (Ci/mL) / injected activity (mCi) / LBM (kg)Ci/mL) / injected activity (mCi) / LBM (kg)

• The arterial SUV (was corrected for blood activity by The arterial SUV (was corrected for blood activity by normalizing it to the average blood SUV estimated from normalizing it to the average blood SUV estimated from the jugular vein to produce a blood-corrected arterial SUV the jugular vein to produce a blood-corrected arterial SUV (arterial tissue-to-background ratio)(arterial tissue-to-background ratio)

mmmm

mmmm

Isotropic resolution of 0.6 mm

SPACE sequence for plaque morphology

FDG-PET Co-Registered to Carotid MRI

Image Analysis and Determinatin of First Order Capillary Transfer Rate Constant

Contrast-Enhancement in Carotid Wall

Kinetic Modeling(Kety-Schmidt Model)

Arterial Input Venous Outflow

Tissue Extraction Tissue Extraction (K(Ktranstrans))

vvbb

Model Parameters Determined by Optimization• vp vascular volume• Ktrans First order blood-to-tissue transfer rate constant

Measured in vessel lumen

ΔCt= vp* ΔCp + KtransCp

Vascular Permeability

Plaque Edema on T2 SPACE and Ktrans

03630993-R

KtransArea under Signal Curve(2 min. post injection)

T2 SPACE

P-NCHLS

High High KKtrans trans in plaque at carotid in plaque at carotid

bifurcationbifurcation

Correlation Between FDG PET and Correlation Between FDG PET and MR Ktrans MR Ktrans

R=0.463P=0.017

ECA

ICAlumen

ICA plaque

Ktrans map of ICA wall and plaque

P-NCHLS-R

Area under SI curve (AUC)(2 min. window)

Complex ICA PlaqueComplex ICA Plaque

Dark-Blood T2-w SPACE

Plaque Edema and Ktrans

16549180-R

Ktrans - ICA SPACE (T2w) ICA

Correspondence between regions with high Correspondence between regions with high SI on T2 SPACE and SI on T2 SPACE and KKtranstrans map of ICA wall map of ICA wall

P-BSHTT-left

Ktrans mapT2 SPACE above carotid

bifurcation

T2 SPACE

Association between Signal Intensity Level in Carotid Association between Signal Intensity Level in Carotid Wall with Wall with T2T2 SPACE and SPACE and KKtranstrans Perfusion Parameter Perfusion Parameter

Correlation of MRI Parametric Maps with Histology

Macrophage Density by Ktrans Macrophage Density by Ktrans CategoriesCategories

R=0.80P=0.03

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

Acknowledgements

• Co-Investigators: Larry Wald (Co-PI), Raymond Kwong, Marcelo Di Carli

• Support through Partners Radiology Research Award