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Background: Intensive lipid-lowering therapy with statins reduces levels of low-density lipoprotein (LDL)-cholesterol (C) and improves plaque volume and composition in patients with cardiovascular disease. Furthermore, rosuvastatin ameliorated carotid stenosis in the ASTEROID study, and altered the composition of plaques in a predominantly Caucasian study population in the ORION study. However, it is not known whether statin therapy achieves similar quantitative improvement in carotid artery plaque in other ethnic groups., Methods and Results: Fifty patients with hypercholesterolemia (LDL-C >or=120 mg/dl) and a maximum carotid intima-media thickness >or=1.8 mm will be enrolled and treated with rosuvastatin at a dose of 5 mg/day for 96 weeks. The primary endpoints will be the percent change of carotid plaque volume and the change in plaque composition after 96 weeks of treatment, as evaluated by magnetic resonance imaging., Conclusions: The CHALLENGER study will provide a noninvasive assessment of the changes in carotid plaque volume and composition achieved by reduction of LDL levels in Japanese patients with carotid stenosis on long-term rosuvastatin therapy.

The purpose of this in vivo MRI study was to quantify changes in atherosclerotic plaque morphology prospectively and to identify factors that may alter the rate of progression in plaque burden. Sixty-eight asymptomatic subjects with >or=50% stenosis, underwent serial carotid MRI examinations over an 18-month period. Clinical risk factors for atherosclerosis, and medications were documented prospectively. The wall and total vessel areas, matched across time-points, were measured from cross-sectional images. The normalized wall index (NWI=wall area/total vessel area), as a marker of disease severity, was documented at baseline and at 18 months. Multiple regression analysis was used to correlate risk factors and morphological features of the plaque with the rate of progression/regression. On average, the wall area increased by 2.2% per year (P=0.001). Multiple regression analysis demonstrated that statin therapy (P=0.01) and a normalized wall index >0.64 (P=0.001) were associated with a significantly reduced rate of progression in mean wall area. All other documented risk factors were not significantly associated with changes in wall area. Findings from this study suggest that increased normalized wall index and the use of statin therapy are associated with reduced rates of plaque progression amongst individuals with advanced, asymptomatic carotid atherosclerosis.

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.

Background and Purpose: MRI is able to quantify carotid plaque size and composition with good accuracy and reproducibility and provides an opportunity to prospectively examine the relationship between plaque features and subsequent cerebrovascular events. We tested the hypothesis that the characteristics of carotid plaque, as assessed by MRI, are possible predictors of future ipsilateral cerebrovascular events., Methods: A total of 154 consecutive subjects who initially had an asymptomatic 50% to 79% carotid stenosis by ultrasound with > or =12 months of follow-up were included in this study. Multicontrast-weighted carotid MRIs were performed at baseline, and participants were followed clinically every 3 months to identify symptoms of cerebrovascular events., Results: Over a mean follow-up period of 38.2 months, 12 carotid cerebrovascular events occurred ipsilateral to the index carotid artery. Cox regression analysis demonstrated a significant association between baseline MRI identification of the following plaque characteristics and subsequent symptoms during follow-up: presence of a thin or ruptured fibrous cap (hazard ratio, 17.0; P< or =0.001), intraplaque hemorrhage (hazard ratio, 5.2; P=0.005), larger mean intraplaque hemorrhage area (hazard ratio for 10 mm2 increase, 2.6; P=0.006), larger maximum %lipid-rich/necrotic core (hazard ratio for 10% increase, 1.6; P=0.004), and larger maximum wall thickness (hazard ratio for a 1-mm increase, 1.6; P=0.008)., Conclusions: Among patients who initially had an asymptomatic 50% to 79% carotid stenosis, arteries with thinned or ruptured fibrous caps, intraplaque hemorrhage, larger maximum %lipid-rich/necrotic cores, and larger maximum wall thickness by MRI were associated with the occurrence of subsequent cerebrovascular events. Findings from this prospective study provide a basis for larger multicenter studies to assess the risk of plaque features for subsequent ischemic events.

MRI is a promising noninvasive technique for characterizing atherosclerotic plaque composition in vivo, with an end-goal of assessing plaque vulnerability. Because of limitations arising from acquisition time, achievable resolution, contrast-to-noise ratio, patient motion, and the effects of blood flow, automatically identifying plaque composition remains a challenging task in vivo. In this article, a segmentation method using maximum a posteriori probability Bayesian theory is presented that divides axial, multi-contrast-weighted images into regions of necrotic core, calcification, loose matrix, and fibrous tissue. Key advantages of the method are that it utilizes morphologic information, such as local wall thickness, and coupled active contours to limit the impact from noise and artifacts associated with in vivo imaging. In experiments involving 142 sets of multi-contrast images from 26 subjects undergoing carotid endarterectomy, segmented areas of each of these tissues per slice agreed with histologically confirmed areas with correlations (R(2)) of 0.78, 0.83, 0.41, and 0.82, respectively. In comparison, manually identifying areas blinded to histology yielded correlations of 0.71, 0.76, 0.33, and 0.78, respectively. These results show that in vivo automatic segmentation of carotid MRI is feasible and comparable to or possibly more accurate than manual review for quantifying plaque composition., (Magn Reson Med, 2006. (c) 2006 Wiley-Liss, Inc.)