MRI and MRA of the Carotid Arteries Robert L. Greenman Department of Radiology Beth Israel Deaconess Medical Center

MRI of the CAROTID ARTERIES Review Pathogenesis/Progression Intima-Media Thickness (IMT) Studies Plaque Constituents Morphology Stable vs Unstable (Vulnerable) Survey of Methods and Results Most Published Results - 1.5T Recent 3T Carotid MRI Studies

MRI of CAROTID ARTERIES Stroke (1999 Statistics) Worldwide 4.4 Million Deaths/Year 5,000 Disabilities/Million Persons United States 750,000 Strokes/Year 1/3 Stroke Patients Die 1/2 of Survivors are Disabled Gorelick, PB, et al Statement from National Stroke Assoc. JAMA 1999; 281:1112-1120

MRI of CAROTID ARTERIES Acute Ischemic Attack Disruption of Atherosclerotic Plaques Cause of many Embolic Strokes

ATHEROSCLEROSIS Intimal Disease Inflammatory Disease Response of the Intima to Injury Ross, R. “Atherosclerosis - An Inflammatory Disease”. N Engl J Med 1999; 340:115-126 Davies, MJ, Woolf, N. “Atherosclerosis: what it is and why does it occur?. Br Heart J; 1993: 69;S 3-11

ARTERIAL PLAQUE COMPOSITION Major Components Lipids Lipid-Containing “Foam Cells” (Macrophages) Macrophages Connective Tissue Matrix Proteins - Collagen Strengthens, Holds Plaque Together Other Components Calcification

ATHEROGENESIS Endothelial Injury/Dysfunction Lipids are a Major Cause of Injury Adhesion and Migration of Luekocytes Immune/Inflammatory Response Migration of Lipids (Normal and Oxidized) Uptake of Lipid by Macrophages Smooth Muscle Proliferation

ATHEROGENESIS Endothelial Injury/Dysfunction Causes Elevated and Modified LDL Free Radicals Cigarette Smoking Hypertension Diabetes Genetic Alterations Infectious Microorganisms

ATHEROGENESIS Endothelial Injury/Dysfunction Immune/Inflammatory Response Increased Adhesiveness Increased Permeability Procoagulant Properties Release of Growth Factors Thickening of Artery Wall and “Remodeling”

ATHEROGENESIS Plaque Formation Modified Lipids Migrate Into Intima Ingested by Macrophages Uptake is Unregulated “Foam Cells” Smooth Muscle Proliferation and Migration Release of Growth Factors

ATHEROGENESIS Plaque Formation Foam Cells Burst - Necrotic Lipid Core Smooth Muscle Proliferation Release of Growth Factors

ATHEROGENESIS Unstable (Vulnerable) Plaque Necrotic Lipid Core Grows Large Fibrous Cap Wears Thin - Ruptures Thrombus

CAROTID PLAQUES Unstable (Vulnerable) Plaque Large Core Necrotic Lipid Intraplaque Hemorrage Unstable Fibrous Cap

CAROTID IMAGING ULTRASOUND Modality of Choice: 2D Ultrasound B-mode Ultrasound Noninvasive Safe Inexpensive Measurements Intima-Media Thickness (IMT) Vessel Geometry Lumen Diameter Distensibility

CAROTID IMT MRI vs US Difficulties with Carotid US Relative position of jawbone WRT bifurcation Vessel tortuosity Calcification Large Intra- and Interobserver Variability

CAROTID IMAGING MRI vs US Little MRA - Mostly MRI Soft Tissue Contrast Lipid, Smooth Muscle, Fibrous Tissue MR Signal Independent of Angle Flow Sensitive Simultaneous Information on: Vessel Lumen Vessel Wall

FSE Black Blood Imaging

T2-W FSE (Dark Blood)

CAROTID IMT MEASUREMENTS Longitudinal Studies Study Progression of Atherosclerosis Risk Factor for Stroke ?? Risk Factor for Cardiovascular Disease ??

CAROTID IMT MEASUREMENTS IMT and Brain Infarction Touboul, et al. Circulation 102:313-318, 2000

CAROTID IMT MEASUREMENTS IMT of Common Carotid Artery Some Studies Suggest IMT Related to Cardiovascular Risk Factors Prevalence of Atherosclerosis of Peripheral Coronary Femoral

CAROTID IMT MEASUREMENTS Increased IMT Associated with Age Howard, et al. 1993 Hypertension Zanchetti, et al. 1998 Diabetes Kawamori, et al. 1992 Hyperlipidemia Poli, et al. 1988 Increased IMT Associated with CAD Crouse, et al. Circulation: 92:1141-1147, 1995

CAROTID IMT MEASUREMENTS Study: Risk Factors that Predict Stroke/MI Iglesias, et al. (Subset “Rotterdam Study”) 374 Subjects - Stroke or MI 1496 Controls Mean Follow-up: 4.2 years Results/Conclusions Significant association between Carotid IMT and Stroke and MI Predictive Value Low When Combined With Other Clinical Observations Iglesias, et al. Stroke: 32:1532-1538, 2001

CAROTID IMT MRI vs US MRI Studies of IMT Measurement Results Crowe, et al. JMRI: 21:282-289, 2005 2D US vs 3D MRI (Black-Blood TSE) 10 Healthy Subjects, 5 Hypertensive Patients Results Bland-Altman Analysis Mean Diff. MRI & US - 1.2% Significant Difference in IMT (P<0.05) Between Hypertensive &Non-Hypertensive for Both Methods

CAROTID IMT MRI vs US Wall Thickness Measurements 3D-TSE MRI vs US Crowe, et al, 2005 JMRI;21:282-289

CAROTID IMT MRI vs US Crowe, et al, 2005 JMRI;21:282-289 Wall Thickness Measurements 3D-TSE MRI vs US Crowe, et al, 2005 JMRI;21:282-289

CAROTID IMT MRI vs US Correlation Study DIR Black Blood MRI vs US 17 Patients Intermediate/High Framingham Cardiovascular Risk Score Results Significant Correlation R = 0.72, p < 0.05 Mani, et al. J Cardiovasc Magn R 8:529-534 2006

CAROTID CE-MRA Identifies Luminal Narrowing Not Plaque Size 100% Sensitivity 92% Specificity Compare to Conventional MRA Wutke, et al. Stroke 33:1522-1529 2002 Not Plaque Size Vessel May Remodel Can Overestimate Extent of Stenosis

Image of the entire vascular region from the aortic arch to the intracranial vessels Wutke, R. et al. Stroke 2002;33:1522-1529 Copyright ©2002 American Heart Association

MRI of CAROTID PLAQUES Non-Invasive MRI Signal Intensities Based on Tissue Biochemical Environment Soft Tissue Contrast Lipid vs Smooth Muscle, Fibrous Tissue Vessel wall/Lumen Contrast Flexibility in Achieving Desired Contrast

MRI of CAROTID PLAQUES Dark Blood Sequences Bright Blood Sequences T2-Weighted T1-Weighted PD- Weighting (Proton Density) Bright Blood Sequences 2D and 3D Time-of-Flight (TOF) Others Magnetization Transfer (MT) Diffusion Sensitive

MRI of CAROTID PLAQUES MRI Contrast of Atherosclerotic Plaque Yuan, C, et al. Radiology 2001; 221:285-299

MRI of CAROTID PLAQUES MRI Contrast Mechanisms Identification of: Lipid Core Calcium Deposits Fibrous Connective Tissue Intraplaque Hemorrhage

1.5T MRI STUDIES Multiple Weightings – T2W, T1W, PDW Shinnar, et al. Arterioscler Thromb Vasc Biol 1999;19:2756-2761 Yuan, et al. Radiology 2001; 221:285-299 Fibrous Cap Thickness Measurement Hatsukami, et al. Circulation 2000;102:959-964 Contrast Enhanced Yuan, et al. J Magn Reson Imaging 2002; 15:62-67

MRI of CAROTID PLAQUES T2-Weighting Delineates Lipid Core and Thrombus Yuan, C, et al. Radiology 2001; 221:285-299

MRI of CAROTID PLAQUES Multiple-Weighting Study Mitsumori, L, et al. JMRI 2003 17:410-420

MRI of CAROTID PLAQUES Multiple-Weighting Study Lipid Core/Fibrous Cap Mitsumori, L, et al. JMRI 2003 17:410-420

MRI of CAROTID PLAQUES Multiple-Weighting Study Pitfall of DIR-BB FSE studies Mitsumori, L, et al. JMRI 2003 17:410-420

MRI of CAROTID PLAQUES Multiple-Weighting Study Calcification Mitsumori, L, et al. JMRI 2003 17:410-420

MRI of CAROTID PLAQUES 3D TOF (Bright Blood) Imaging Parameters: Bright Lumen/Dark Fibrous Tissue Identify Unstable Fibrous Caps in vivo Imaging Parameters: TR = 23 ms TE = 3.8 ms 2 Signal Averages Scan Time = 2 - 4 Min.

MRI of CAROTID PLAQUES 3D TOF (Bright Blood) Spatial Resolution Slice Thickness = 2 mm Acquisition Matrix: Size = 256 x 256 Voxel Size = 0.5 x 0.5 x 2 mm Zero Filled: Matrix = 512 x 512 Zero Filled Voxel Size = 0.25 x 0.25 x 2 mm

MRI of CAROTID PLAQUES 3D TOF (Bright Blood) Unstable Fibrous Cap Detection Yuan, C, et al. Radiology 2001; 221:285-299

MRI of Neovasculature Neovasculature in Plaques Associated with Infiltration of Inflammatory Cells Plaque Destabilization Involved In Recruitment of Leukocytes Inflammatory Cells Present at Rupture Sites Measurement of Neovasculature may Identify Vulnerable Plaques Contrast-Enhanced MRI

MRI of Neovasculature MRI of Neovasculature Kerwin, et al. Circulation 107:851-856 2003

1.5T to 3.0T Comparisons All Studies Evaluated Black-Blood Anumula, et al, Acad Radiol;2006 12:1521-1526 Compared Multi-coil Arrays Univ. Pennsylvania (FW Wehrli) Yarnykh, et al, JMRI;2006 23:691-698 Compared Multicontrast Univ. Washington (C. Yuan) Koktzoglou, et al,JMRI;2006 23:699-705 Compared Multi-slice Northwestern & Mt Sinai (L Debiao, ZA Fayad) Greenman, et al. MRI 2007 In Press Vessel Wall Sharpness with Field Strength and Spatial Resolution

1.5T to 3.0T Comparisons Conclusions of studies 3.0T Improves SNR CNR SNR can be traded for higher spatial resolution

Purpose Apply Edge Detection to Evaluate effect of Spatial Resolution Static Field Strength Carotid Imaging Methods: 2D-TOF (GRE) 2D Black-Blood (Double-IR FSE)

Edge Detection Have Been Used to Evaluate and Compare Vessel Edge Definition Coronary Arteries (Bright Blood) Compare Results of Acquisition Schemes Deriche Algorithm First-order derivative Create derivative or “edge” images Vessel sharpness: “The average edge value along the calculated vessel border” … “Higher edge values correspond to better vessel definition.” Botnar, et al, Circulation 1999;99:3139-3148 Weber, et al, JMRI 2004;20:395-402 Deriche, R, IEEE Trans PAMI. 1990;12:78-87 (“Fast algorithms for low-level vision”)

METHODS Compared Spatial Resolution/Field Strength: 0.27 mm X 0.27 mm X 2.0 mm 1.5T and 3.0T; n = 12 (1.5T-H, 3.0T-H) 0.55 mm x 0.55 mm x 2.0 mm (Zero-Filled 2X) 1.5T only; n= 5 (1.5T-L) 2D DIR Black Blood FSE 2D Gradient Echo Time-of-Flight

2D-TOF Results

DIR-BB Results

Gradient Value Comparison

Carotid Edge Values

MRI of CAROTID PLAQUES Identify Stable/Unstable Plaques Follow Progression of Plaque Development Monitor Therapies

CONCLUSIONS 3.0 Tesla MRI Offers Improved Signal-to-Noise Ratio – Resolution IMT Measurements May Be Able To Identify Unstable Plaques Improved Accuracy: Measurement Cap Thickness May Improve Monitoring of Interventional Therapies