William S. Kerwin

In Vivo Quantitative Measurement of Intact Fibrous Cap and Lipid-Rich Necrotic Core Size in Atherosclerotic Carotid Plaque: Comparison of High-Resolution, Contrast-Enhanced Magnetic Resonance Imaging and Histology

Background— Previous studies with contrast-enhanced magnetic resonance imaging (CEMRI) have shown that the fibrous cap (FC) in atherosclerotic carotid plaques enhances with gadolinium-based contrast agents. Conversely, the lipid-rich necrotic core (LR-NC), lacking both vasculature and matrix, shows no or only slight enhancement. The goal of this study was to assess whether CEMRI can be used to accurately measure the dimensions of the intact FC and LR-NC. Methods and Results— Twenty-one patients scheduled for carotid endarterectomy were imaged with a 1.5-T scanner. Precontrast images and CEMRI were obtained. One hundred eight locations with an intact FC were matched between MRI and the excised histology specimens. Quantitative measurements of FC length along the lumen circumference, FC area, and LR-NC area were collected from CEMRI images and histology sections. Blinded comparison of corresponding MR images and histology slices showed moderate to good correlation for length (r=0.73, P<0.001) and area (r=0.80, P<0.001) of the intact FC. The mean percentage LR-NC areas (LR-NC area/wall area) measured by CEMRI and histology were 30.1% and 32.7%, respectively, and were strongly correlated across locations (r=0.87, P<0.001). Conclusions— In vivo high-resolution CEMRI is capable of quantitatively measuring the dimensions of the intact FC and LR-NC. These new parameters may be useful to evaluate plaque vulnerability and provide continuous variables for characterizing the intact FC and LR-NC in progression and regression studies.

Contrast-enhanced high resolution MRI for atherosclerotic carotid artery tissue characterization.

To determine if a gadolinium‐based contrast agent provides additional information for characterization of human plaque tissues, particularly neovasculature. Although high‐resolution magnetic resonance imaging (MRI) has been used to identify plaque constituents in advanced atherosclerosis, some constituents, such as neovascularized tissue, defy detection.

Hemorrhage in the Atherosclerotic Carotid Plaque: A High-Resolution MRI Study

Background and Purpose— High-resolution, multicontrast magnetic resonance imaging (MRI) has developed into an effective tool for the identification of carotid atherosclerotic plaque components, such as necrotic core, fibrous matrix, and hemorrhage/thrombus. Factors that may lead to plaque instability are lipid content, thin fibrous cap, and intraplaque hemorrhage. Determining the age of intraplaque hemorrhage can give insight to the history and current condition of the biologically active plaque. The aim of this study was to develop criteria for the identification of the stages of intraplaque hemorrhage using high-resolution MRI. Methods— Twenty-seven patients, scheduled for carotid endarterectomy (CEA), were imaged on a 1.5-T GE SIGNA scanner (sequences: 3-dimensional time of flight, double-inversion recovery, T1-weighted (T1W), PDW and T2W). Two readers, blinded to histology, reviewed MR images and grouped hemorrhage into fresh, recent, and old categories using a modified cerebral hemorrhage criteria. The CEA specimens were serially sectioned and graded as to presence and stage of hemorrhage. Results— Hemorrhage was histologically identified and staged in 145/189 (77%) of carotid artery plaque locations. MRI detected intraplaque hemorrhage with high sensitivity (90%) but moderate specificity (74%). Moderate agreement in classifying stages occurred between MRI and histology (Cohen κ = 0.7, 95% CI: 0.5 to 0.8 for reviewer 1 and 0.4, 95% CI: 0.2 to 0.6 for reviewer 2), with moderate agreement between the 2 MRI readers (κ = 0.4, 95% CI: 0.3 to 0.6). Conclusion— Multicontrast MRI can detect and classify carotid intraplaque hemorrhage with high sensitivity and moderate specificity.

Quantitative Magnetic Resonance Imaging Analysis of Neovasculature Volume in Carotid Atherosclerotic Plaque

Background—Neovasculature within atherosclerotic plaques is believed to be associated with infiltration of inflammatory cells and plaque destabilization. The aim of the present investigation was to determine whether the amount of neovasculature present in advanced carotid plaques can be noninvasively measured by dynamic, contrast-enhanced MRI. Methods and Results—A total of 20 consecutive patients scheduled for carotid endarterectomy were recruited to participate in an MRI study. Images were obtained at 15-second intervals, and a gadolinium contrast agent was injected coincident with the second of 10 images in the sequence. The resulting image intensity within the plaque was tracked over time, and a kinetic model was used to estimate the fractional blood volume. For validation, matched sections from subsequent endarterectomy were stained with ULEX and CD-31 antibody to highlight microvessels. Finally, all microvessels within the matched sections were identified, and their total area was computed as a fraction of the plaque area. Results were obtained from 16 participants, which showed fractional blood volumes ranging from 2% to 41%. These levels were significantly higher than the histological measurements of fractional vascular area. Nevertheless, the 2 measurements were highly correlated, with a correlation coefficient of 0.80 (P <0.001). Conclusions—Dynamic contrast-enhanced MRI provides an indication of the extent of neovasculature within carotid atherosclerotic plaque. MRI therefore provides a means for prospectively studying the link between neovasculature and plaque vulnerability.

In vivo accuracy of multisequence MR imaging for identifying unstable fibrous caps in advanced human carotid plaques.

To evaluate the in vivo accuracy of a multisequence MRI technique for prospectively identifying one feature of the vulnerable plaque—an unstable fibrous cap—in human carotid atherosclerosis.

Differentiation of Intraplaque Versus Juxtaluminal Hemorrhage/Thrombus in Advanced Human Carotid Atherosclerotic Lesions by In Vivo Magnetic Resonance Imaging

Background—Intraplaque hemorrhage and juxtaluminal hemorrhage/thrombus may differ in cause and clinical implications. This study tested the hypothesis that MRI can distinguish between intraplaque hemorrhage and juxtaluminal hemorrhage/thrombus and investigated the association between hemorrhage and underlying lesion types. Methods and Results—Twenty-six patients scheduled for carotid endarterectomy were imaged with a 1.5-T GE scanner by a multicontrast-weighted MRI technique. Hemorrhages were identified with previously established MRI criteria, and differentiations were made between intraplaque and juxtaluminal hemorrhage/thrombus. Corresponding histology was used to confirm the magnetic resonance findings. Tissues underlying areas of hemorrhage/thrombus were histologically categorized according to modified American Heart Association criteria. Of 190 matched sections, 140 contained areas of hemorrhage by histology, of which MRI correctly detected 134. The sensitivity and specificity for MRI to correctly identify cross sections that contained hemorrhage were 96% and 82%, respectively. Furthermore, MRI was able to distinguish juxtaluminal hemorrhage/thrombus from intraplaque hemorrhage with an accuracy of 96%. The distribution of lesion types underlying hemorrhages differed significantly (P=0.004). Intraplaque hemorrhage had an underlying lipid-rich type IV/V lesion in 55% of histological sections, whereas juxtaluminal hemorrhage/thrombus had an underlying calcified lesion type VII in 70% of sections. Conclusions—In vivo high-resolution MRI can detect and differentiate intraplaque hemorrhage from juxtaluminal hemorrhage/thrombus with good accuracy. The association of hemorrhage and lesion types suggests potential differences in origin. Noninvasive MRI therefore provides a possible tool for prospectively studying differences in origin of plaque hemorrhage and the association of plaque progression and instability.

Carotid Plaque Composition Differs Between Ethno-Racial Groups An MRI Pilot Study Comparing Mainland Chinese and American Caucasian Patients

Objective—Ethnicity-based research may identify new clues to the pathogenesis of atherosclerotic disease. Therefore, we sought to determine whether carotid lesions differ between 20 Chinese and 20 Caucasian Americans by MRI. Methods and Results—Inclusion criteria were >50% stenosis as measured by duplex ultrasound and recent symptoms attributed to carotid artery disease. The patients were imaged in 2 centers (Beijing, China and Seattle, Wash) using a standardized protocol. Both carotid arteries were reviewed quantitatively (lumen, wall, outer wall, tissue components) and morphologically (lesion types, fibrous cap status). Significant differences between the Chinese and Americans were found for the mean size of the lipid/necrotic core (13.6 versus 7.8 mm2; P=0.002), percentage of slices with calcified type VII lesions (1.6 versus 12.4%; P=0.03), and percentage of slices with early type III lesions (19.3 versus 9.3%; P=0.02). Furthermore, the mean outer wall area in the common carotid artery was larger in the Chinese population (P=0.007). Conclusions—This pilot study suggests that composition and morphology of atherosclerotic lesions in symptomatic carotid disease differ between ethno-racial groups. Quantitative MRI-based review of carotid atherosclerosis comparing plaque morphology and composition between ethno-racial groups is feasible, and future MRI studies may improve our understanding of the pathophysiology of this disease.

MR imaging of adventitial vasa vasorum in carotid atherosclerosis

Vasa vasorum in the adventitia of atherosclerotic arteries may play a role in plaque progression. In this investigation, a method for characterizing vasa vasorum in the carotid artery is proposed, in which the perfusion properties of the adventitia are probed via dynamic contrast‐enhanced (DCE) MRI. A parametric “vasa vasorum image” is automatically generated that depicts the plasma volume (vp) and transfer constant (Ktrans). The average Ktrans within the adventitia is proposed as a quantitative measurement related to the extent of the vasa vasorum. In 25 subjects with lesions meeting the requirements for carotid endarterectomy (CEA) significantly higher adventitial Ktrans of 0.155 ± 0.045 min–1 was observed, compared to 0.122 ± 0.029 min–1 in the remaining 20 subjects with moderate disease (P < 0.01). In the 25 subjects with endarterectomy specimens, histological evaluation showed that adventitial Ktrans was significantly correlated with the amount of neovasculature (R = 0.41; P = 0.04) and macrophages (R = 0.49; P = 0.01) in the excised plaque. In the remaining 20 subjects without histology, elevated adventitial Ktrans was significantly correlated with the log of C‐reactive protein (CRP) levels (R = 0.57; P = 0.01) and was elevated in active smokers compared to nonsmokers (0.141 ± 0.036 vs. 0.111 ± 0.017 min–1; P = 0.02). Because these factors are all associated with higher risk of atherosclerotic complications, these results suggest that adventitial Ktrans may be a marker of risk as well. Magn Reson Med 59:507–514, 2008.

Magnetic Resonance Imaging of Carotid Atherosclerosis: Plaque Analysis

Objectives: The Computer-Aided System for CArdiovascular Disease Evaluation (CASCADE) has been developed for streamlined, automated analysis of carotid artery magnetic resonance imaging to measure atherosclerotic plaque burden and composition in vivo. The purpose of this investigation was to assess the performance of CASCADE compared with manual outlining. Methods: Magnetic resonance images were obtained from 26 subjects with 16% to 79% carotid artery stenosis by duplex ultrasound who were imaged twice in a 2-week period with a multiple-slice, multiple-contrast magnetic resonance imaging protocol as part of the Outcome of Rosuvastatin treatment on carotid artery atheroma: a magnetic resonance Imaging ObservatioN trial. Manual outlining was used to identify the boundaries of the lumen, wall, necrotic core (NC), and calcifications. After 6 months, the analysis was repeated using CASCADE. For each data set, the contours were used to compute the maximal normalized wall index (NWI; wall area divided by total vessel area), maximal wall thickness (WT), and the average NC and calcified (CA) areas per slice. Agreement between manual and automated reviews and the scan-scan measurement reproducibilities were evaluated. Results: Pearson correlation between manual and automated analyses was 0.94 for maximal NWI, 0.86 for maximal WT, 0.84 for NC, and 0.96 for CA. Intraclass correlation coefficients for manual and automated analyses were 0.90 and 0.97 for maximal NWI, 0.89 and 0.95 for maximal WT, 0.95 and 0.87 for NC, and 0.96 and 0.94 for CA, respectively. Conclusions: Automated analysis tools are capable of providing accurate and reproducible measurements of carotid atherosclerotic burden and composition when compared with manually outlined results.

MRI of Atherosclerosis

The emergence of high‐resolution, rapid imaging methods has enabled MRI to noninvasively image the fine internal structure of atherosclerotic artery walls. This capability has, in turn, captured the interest of clinicians, who see it as an opportunity to assess disease severity based on the characteristics of atherosclerotic lesions themselves, rather than only their effects on the vessel lumen. MRI of atherosclerosis thus has the potential to be used in medical treatment decisions or to assess the effects of experimental treatment options. Given this potential, a number of research groups have been investigating MRI of atherosclerosis in an effort to establish the ability of MRI to determine atherosclerotic plaque burden, detect plaque composition, and ultimately identify vulnerable plaque before it leads to a clinical event. In this review, the current state of the art is summarized for the three primary vessel targets: the carotid artery, the aorta, and the coronary arteries. J. Magn. Reson. Imaging 2004;19:710–719.