Baocheng Chu

Association Between Carotid Plaque Characteristics and Subsequent Ischemic Cerebrovascular Events A Prospective Assessment With MRI—Initial 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 ≥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≤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.

Presence of Intraplaque Hemorrhage Stimulates Progression of Carotid Atherosclerotic Plaques A High-Resolution Magnetic Resonance Imaging Study

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. The volumes of wall, lumen, lipid-rich necrotic core, calcification, and intraplaque hemorrhage were measured with a custom-designed image analysis tool. The percent change in wall volume (6.8% versus −0.15%; P=0.009) and lipid-rich necrotic core volume (28.4% versus −5.2%; P=0.001) was significantly higher in the hemorrhage group than in controls over the course of the study. Furthermore, those with intraplaque hemorrhage at baseline were much more likely to have new plaque hemorrhages at 18 months compared with controls (43% versus 0%; P=0.006). Conclusions—Hemorrhage into the carotid atherosclerotic plaque accelerated plaque progression in an 18-month period. Repeated bleeding into the plaque may produce a stimulus for the progression of atherosclerosis by increasing lipid core and plaque volume and creating new destabilizing factors.

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.

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.

Effect of rosuvastatin therapy on carotid plaque morphology and composition in moderately hypercholesterolemic patients: a high-resolution magnetic resonance imaging trial.

BACKGROUND Magnetic resonance imaging (MRI) can noninvasively assess changes in atherosclerotic plaque morphology and composition. The ORION trial assessed the effects of rosuvastatin on carotid plaque volume and composition. METHODS The randomized, double-blind ORION trial used 1.5-T MRI to image carotid atherosclerotic plaques at baseline and after 24 months of treatment. Forty-three patients with fasting low-density lipoprotein cholesterol > or = 100 and < 250 mg/dL and 16% to 79% carotid stenosis by duplex ultrasound were randomized to receive either a low (5 mg) or high (40/80 mg) dose of rosuvastatin. RESULTS After 24 months, 33 patients had matched serial MRI scans to compare by reviewers blinded to clinical data, dosage, and temporal sequence of scans. Low-density lipoprotein cholesterol was significantly reduced from baseline in both the low- and high-dose groups (38.2% and 59.9%, respectively, both P < .001). At 24 months, there were no significant changes in carotid plaque volume for either dosage group. In all patients with a lipid-rich necrotic core (LRNC) at baseline, the mean proportion of the vessel wall composed of LRNC (%LRNC) decreased by 41.4% (P = .005). CONCLUSIONS In patients with moderate hypercholesterolemia, both low- and high-dose rosuvastatin were effective in reducing low-density lipoprotein cholesterol. Furthermore, rosuvastatin was associated with a reduction in %LRNC, whereas the overall plaque burden remained unchanged over the course of 2 years of treatment. These findings provide evidence that statin therapy may have a beneficial effect on plaque volume and composition, as assessed by noninvasive MRI.

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.

Improved suppression of plaque‐mimicking artifacts in black‐blood carotid atherosclerosis imaging using a multislice motion‐sensitized driven‐equilibrium (MSDE) turbo spin‐echo (TSE) sequence

In this study, a turbo spin‐echo (TSE) based motion‐sensitized driven‐equilibrium (MSDE) sequence was used as an alternative black‐blood (BB) carotid MRI imaging scheme. The MSDE sequence was first optimized for more efficient residual blood signal suppression in the carotid bulb of healthy volunteers. Effective contrast‐to‐noise ratio (CNReff) and residual signal‐to‐noise ratio (SNR) in the lumen measured from MSDE images were then compared to those measured from inflow saturation (IS) and double inversion‐recovery (DIR) images. Statistically significant higher CNReff and lower lumen SNR were obtained from MSDE images. To assess MSDE sequence in a clinical carotid protocol, 42 locations from six subjects with 50% to 79% carotid stenosis by duplex ultrasound were scanned with both MSDE and multislice DIR. The comparison showed that MSDE images present significantly higher CNR and lower lumen SNR compared to corresponding multislice DIR images. The vessel wall area and mean wall thickness measurements in MSDE images were slightly but significantly lower than those obtained with other blood suppression techniques. In conclusion, in vivo comparisons demonstrated that MSDE sequence can achieve better blood suppression and provide a more accurate depiction of the lumen boundaries by eliminating plaque mimicking artifacts in carotid artery (CA) imaging. Magn Reson Med 58:973–981, 2007.

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.

Prevalence of American Heart Association type VI carotid atherosclerotic lesions identified by magnetic resonance imaging for different levels of stenosis as measured by duplex ultrasound.

OBJECTIVES Via magnetic resonance imaging (MRI), we sought to determine the prevalence of atherosclerotic American Heart Association type VI lesions (AHA-LT6) (lesions with luminal surface defect, hemorrhage/thrombus, or calcified nodule) in carotid arteries that represented all categories of stenosis as measured by duplex ultrasound. BACKGROUND Arterial stenosis alone has been shown to be a poor predictor of cardiovascular events. Autopsy studies suggest that features associated with AHA-LT6 lesions, rather than the degree of luminal narrowing, characterize the high-risk plaque. METHODS A total of 192 subjects underwent bilateral carotid artery magnetic resonance imaging (MRI) scans at 1.5T after evaluation with ultrasound to determine stenosis. After excluding arteries with a previous endarterectomy, poor image quality, or missing ultrasound data, there were 175 patients with 260 arteries available for analysis. The AHA lesion type was determined by the consensus opinion of 2 experienced carotid MRI reviewers. RESULTS In total, 96 of 260 (37.0%) arteries had >or=1 location with AHA-LT6. Of the arteries with AHA-LT6, 84.4% had hemorrhage, 45.8% had a ruptured fibrous cap, and 14.6% showed other type of complications. Prevalence of AHA-LT6 was an increasing sequence of 8.1% in the 37 arteries with 1% to 15% stenosis, 21.7% in the 60 arteries with 16% to 49% stenosis, 36.8% in the 114 arteries with 50% to 79% stenosis, and 77.6% in the 49 arteries with 80% to 99% stenosis. CONCLUSIONS Complicated AHA-LT6 are frequently found in arteries with <or=50% stenosis. These findings indicate that complex lesions develop in a substantial number of arteries in the absence of high-grade stenosis. Ongoing prospective studies will determine the predictive value of vulnerable plaque features, as visualized by MRI, for risk of subsequent ischemic events.

Sample Size Calculation for Clinical Trials Using Magnetic Resonance Imaging for the Quantitative Assessment of Carotid Atherosclerosis

PURPOSE To provide sample size calculation for the quantitative assessment of carotid atherosclerotic plaque using non-invasive magnetic resonance imaging in multi-center clinical trials. METHODS. As part of a broader double-blind randomized trial of an experimental pharmaceutical agent, 20 asymptomatic placebo-control subjects were recruited from 5 clinical sites for a multi-center study. Subjects had 4 scans in 13 weeks on GE 1.5 T scanners, using TOF, T1-/PD-/T2- and contrast-enhanced Tl-weighted images. Measurement variability was assessed by comparing quantitative data from the index carotid artery over the four time points. The wall/outer wall (W/OW) ratio was calculated as wall volume divided by outer wall volume. The percent lipid-rich/necrotic core (%LR/NC) and calcification (%Ca) were measured as a proportion of the vessel wall. For %LR/NC and %Ca, only those subjects that exhibited LR/NC or Ca components were used in the analysis. RESULTS Measurement error was 5.8% for wall volume, 3.2% for W/OW ratio, 11.1% for %LR/NC volume and 18.6% for %Ca volume. Power analysis based on these values shows that a study with 14 participants in each group could detect a 5% change in W/OW ratio, 10% change in wall volume, and 20% change in %LR/NC volume (power = 80%, p < .05). The calculated measurement errors presume any true biological changes were negligible over the 3 months that subjects received placebo. CONCLUSION In vivo MRI is capable of quantifying plaque volume and plaque composition, such as %lipid-rich/necrotic core and %calcification, in the clinical setting of a multi-center trial with low inter-scan variability. This study provides the basis for sample size calculation of future MRI trials.