Background-High-resolution MRI has been shown to be capable of identifying plaque constituents, such as the necrotic core and intraplaque hemorrhage, in human carotid atherosclerosis. The purpose of this study was to evaluate differential contrast-weighted images, specifically a multispectral MR technique, to improve the accuracy of identifying the lipid-rich necrotic core and acute intraplaque hemorrhage in vivo. Methods and Results-Eighteen patients scheduled for carotid endarterectomy underwent a preoperative carotid MRI examination in a 1.5-T GE Signa scanner using a protocol that generated 4 contrast weightings (T1, T2, proton density, and 3D time of flight). MR images of the vessel wall were examined for the presence of a lipid-rich necrotic core and/or intraplaque hemorrhage. Ninety cross sections were compared with matched histological sections of the excised specimen in a double-blinded fashion. Overall accuracy (95% CI) of multispectral MRI was 87% (80% to 94%), sensitivity was 85% (78% to 92%), and specificity was 92% (86% to 98%). There was good agreement between MRI and histological findings, with a value of ϭ0.69 (0.53 to 0.85). Conclusions-Multispectral MRI can identify the lipid-rich necrotic core in human carotid atherosclerosis in vivo with high sensitivity and specificity. This MRI technique provides a noninvasive tool to study the pathogenesis and natural history of carotid atherosclerosis. Furthermore, it will permit a direct assessment of the effect of pharmacological therapy, such as aggressive lipid lowering, on plaque lipid composition.
Objective-This study evaluates the ability of MRI to quantify all major carotid atherosclerotic plaque components in vivo. Methods and Results-Thirty-one subjects scheduled for carotid endarterectomy were imaged with a 1.5T scanner using time-of-flight-, T1-, proton density-, and T2-weighted images. A total of 214 MR imaging locations were matched to corresponding histology sections. For MRI and histology, area measurements of the major plaque components such as lipid-rich/necrotic core (LR/NC), calcification, loose matrix, and dense (fibrous) tissue were recorded as percentages of the total wall area. Intraclass correlation coefficients (ICCs) were computed to determine intrareader and inter-reader reproducibility. Key Words: atherosclerosis Ⅲ magnetic resonance imaging Ⅲ carotid artery Ⅲ plaque A therosclerosis and its thrombotic complications are the leading cause of morbidity and mortality in industrialized countries. Therefore, the need for new medical therapies and technology to treat and prevent cardiovascular atherosclerotic disease is enormous.Accurate information of atherosclerotic plaque morphology and plaque composition is necessary to identify the "vulnerable plaques" that are likely to cause embolic events. A noninvasive imaging modality that could provide such information would be an invaluable tool in studies of the relationship between plaque composition/morphology and plaque progression/regression. Furthermore, such imaging techniques may be used in clinical trials to monitor the effects of drugs on diseased arteries.B-Mode ultrasonography has been used widely in plaque progression/regression trials that involve either lipidlowering drugs or calcium channel blockers. 1 However, this modality is highly operator dependent, has limited soft tissue contrast, and requires a large number of subjects to detect a significant change in the intima-media thickness. 1 Intravascular ultrasound (IVUS) is used increasingly in atherosclerosis regression/progression trials that study coronary arteries. 2 Although IVUS is highly reproducible 3 and provides tomographic information about the vessel wall, 3 it is an invasive procedure and has limited capacity to discriminate between fibrous and fatty plaques. 4 Recent publications 5-11 have shown that in vivo MRI can identify the main components of the atherosclerotic plaque such as the lipid-rich/necrotic core (LR/NC), calcification, and hemorrhage. In addition, morphological information about the status of the fibrous cap 12 and the American Heart Association (AHA) lesion type 13 can be obtained noninvasively. Moreover, the tomographic orientation of MRI enables the full cross-sectional view of the vessel wall, which can be measured accurately 14 and reproducibly. 15 It has been demonstrated that ex vivo MRI of endarterectomy specimen is able to identify 16 and quantify 17,18 plaque components with high diagnostic accuracy. This study is aimed at evaluating the ability of MRI to quantify all major carotid atherosclerotic plaque components in vivo, using histolog...
Background-Recent studies demonstrated that in vivo and ex vivo MRI can characterize the components of the carotid atherosclerotic plaque, such as fibrous tissue, lipid/necrotic core, calcium, hemorrhage, and thrombus. The purpose of this study was to determine whether in vivo high-resolution multicontrast MRI could accurately classify human carotid atherosclerotic plaque according to the American Heart Association classification. Methods and Results-Sixty consecutive patients (mean age 70 years; 54 males) scheduled for carotid endarterectomy were imaged with a 1.5-T scanner after informed consent was obtained. A standardized protocol was used to obtain 4 different contrast-weighted images (time of flight and T1-, PD-, and T2-weighted) of the carotid arteries. Best voxel size was 0.25ϫ0.25ϫ1 mm 3 . Carotid plaques were removed intact and processed for histological examination. Both MR images and histological sections were independently reviewed, categorized, and compared. Overall, the classification obtained by MRI and the American Heart Association classifications showed good agreement, with Cohen's (95% CI) of 0.74 (0.67 to 0.82) and weighted of 0.79. The sensitivity and specificity, respectively, of MRI classification were as follows: type I-II lesions, 67% and 100%; type III lesions, 81% and 98%; type IV-V lesions, 84% and 90%; type VI lesions, 82% and 91%; type VII lesions, 80% and 94%; and type VIII lesions, 56% and 100%. Conclusions-In vivo high-resolution multicontrast MRI is capable of classifying intermediate to advanced atherosclerotic lesions in the human carotid artery and is also capable of distinguishing advanced lesions from early and intermediate atherosclerotic plaque.
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.
Background-Previous studies suggest that erythrocyte membranes from intraplaque hemorrhage into the necrotic core are a source of free cholesterol and may become a driving force in the progression of atherosclerosis. We have shown that MRI can accurately identify carotid intraplaque hemorrhage and precisely measure plaque volume. We tested the hypothesis that hemorrhage into carotid atheroma stimulates plaque progression. Methods and Results-Twenty-nine subjects (14 cases with intraplaque hemorrhage and 15 controls with comparably sized plaques without intraplaque hemorrhage at baseline) underwent serial carotid MRI examination with a multicontrast weighted protocol (T1, T2, proton density, and 3D time of flight) over a period of 18 months.
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 ϭ0.7, 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 (ϭ0.4, 95% CI: 0.3 to 0.6). Conclusion-Multicontrast MRI can detect and classify carotid intraplaque hemorrhage with high sensitivity and moderate specificity.
Endothelial attachment is the initial step in leukocyte recruitment into developing atherosclerotic lesions. To determine whether vascular cell adhesion molecule-i (VCAM-1) expression may play a role in inflammatory cell recruitment into human atherosclerotic lesions, immunohistochemistry was performed with a polyclonal rabbit antisera, raised against recombinant human VCAM-1, on 24 atherosclerotic coronary plaques and 11 control coronary segments with nonatherosclerotic diffuse intimal thickening from 10 patients. Immunophenotyping was performed on adjacent sections to identify smooth muscle cells, macrophages, and endothelial cells. To confirm VCAM-1-expressing cell types, double immunostaining with VCAM-1 antisera and each of the cell-specific markers and in situ hybridization were performed.All atherosclerotic plaques contained some VCAM-1, compared to 45% of control segments. VCAM-1 was found infrequently on endothelial cells at the arterial lumen in both plaques (21%) and in control segments (27%), but was prevalent in areas of neovascularization and inflammatory infiltrate in the base of plaques. Double immunostaining and in situ hybridization confirmed that most VCAM-1 was expressed by subsets of plaque smooth muscle cells and macrophages. The results document the presence of VCAM-1 in human atherosclerosis, demonstrate VCAM-1 expression by human smooth muscle cells in vivo, and suggest that intimal neovasculature may be an important site of inflammatory cell recruitment into advanced coronary lesions. (J. Clin. Invest. 1993.92:945-951.)
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 (PϽ0.001). 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. Key Words: magnetic resonance imaging Ⅲ contrast media Ⅲ carotid arteries Ⅲ atherosclerosis R ecent investigations have targeted neovasculature as an important factor contributing to atherosclerotic plaque vulnerability. Zamir and Silver 1 speculated that the presence of neovasculature within coronary artery walls may play a role in the pathogenesis of vascular disease. Kumamoto et al 2 showed that intimal neovasculature arising from the adventitial vasa vasorum was associated with inflammatory infiltrate. A role for neovasculature in the recruitment of leukocytes to the shoulder regions of lipid-rich plaques was proposed by de Boer et al. 3 Because such inflammatory cells are present at the sites of plaque rupture, 4 neovasculature may be a contributor to or a marker for vulnerable plaque. Support for this claim is provided by Mofidi et al, 5 who found higher microvessel counts in carotid endarterectomy specimens from symptomatic patients than from asymptomatic ones. Similarly, McCarthy et al 6 found microvessels in symptomatic patients were larger and more irregular in shape.These studies suggest that an imaging tool capable of measuring the extent of plaque neovasculature could be invaluable for identifying high-risk plaques or assessing the response to plaque-stabilizing therapies. A strong contender for measuring plaque neovasculature is MRI using an intravenously injected contrast-enhancing agent. Contrastenhanced (CE) MRI h...
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