Nayak L. Polissar

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.

Classification of Human Carotid Atherosclerotic Lesions With In Vivo Multicontrast Magnetic Resonance Imaging

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 0.25×0.25×1 mm3. 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 &kgr; (95% CI) of 0.74 (0.67 to 0.82) and weighted &kgr; 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.

Visualization of Fibrous Cap Thickness and Rupture in Human Atherosclerotic Carotid Plaque In Vivo With High-Resolution Magnetic Resonance Imaging

BackgroundThe results of studies of advanced lesions of atherosclerosis suggest that the thickness of the fibrous cap that overlies the necrotic core distinguishes the stable lesion from one that is at high risk for rupture and thromboembolic events. We have developed a high-resolution MRI technique that can identify the fine structure of the lesion, including the fibrous cap, in vivo. The aim of the present study was to determine the agreement between in vivo MRI and lesion architecture as seen on histology and gross tissue examination to identify fibrous cap thickness and rupture. Methods and ResultsTwenty-two subjects who were scheduled for carotid endarterectomy underwent MRI with a 3-dimensional multiple overlapping thin slab angiography protocol. The appearance of the fibrous cap was categorized as (1) an intact, thick, (2) an intact, thin, or (3) a ruptured fibrous cap on MRI, gross, and histological sections. Thirty-six sites were available for comparison between MRI and histology. There was a high level of agreement between MRI and histological findings: 89% agreement, &kgr; (95% CI)=0.83 (0.67 to 1.0), weighted &kgr;=0.87. Spearman’s correlation coefficient was 0.88 (significant to the 0.01 level). ConclusionsThese findings indicate that high-resolution MRI with a 3-dimensional multiple overlapping thin slab angiography protocol is capable of distinguishing intact, thick fibrous caps from intact thin and disrupted caps in atherosclerotic human carotid arteries in vivo. This noninvasive technique has the potential to permit studies that examine the relationship between fibrous cap changes and clinical outcome and to permit trials that evaluate therapy intended to “stabilize” the fibrous cap.

Quantitative Evaluation of Carotid Plaque Composition by In Vivo MRI

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. MRI measurements of plaque composition were statistically equivalent to those of histology for the LR/NC (23.7 versus 20.3%; P=0.1), loose matrix (5.1 versus 6.3%; P=0.1), and dense (fibrous) tissue (66.3% versus 64%; P=0.4). Calcification differed significantly when measured as a percentage of wall area (9.4 versus 5%; P<0.001). Intrareader and inter-reader reproducibility was good to excellent for all tissue components, with ICCs ranging from 0.73 to 0.95. Conclusions— MRI-based tissue quantification is accurate and reproducible. This application can be used in therapeutic clinical trials and in prospective longitudinal studies to examine carotid atherosclerotic plaque progression and regression.

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.

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.

Prospective Study of Atherosclerotic Disease Progression in the Renal Artery

BACKGROUND The aim of this study was to determine the incidence of and the risk factors associated with progression of renal artery disease in individuals with atherosclerotic renal artery stenosis (ARAS). METHODS AND RESULTS Subjects with >/=1 ARAS were monitored with serial renal artery duplex scans. A total of 295 kidneys in 170 patients were monitored for a mean of 33 months. Overall, the cumulative incidence of ARAS progression was 35% at 3 years and 51% at 5 years. The 3-year cumulative incidence of renal artery disease progression stratified by baseline disease classification was 18%, 28%, and 49% for renal arteries initially classified as normal, <60% stenosis, and >/=60% stenosis, respectively (P=0.03, log-rank test). There were only 9 renal artery occlusions during the study, all of which occurred in renal arteries having >/=60% stenosis at the examination before the detection of occlusion. A stepwise Cox proportional hazards model included 4 baseline factors that were significantly associated with the risk of renal artery disease progression during follow-up: systolic blood pressure >/=160 mm Hg (relative risk [RR]=2.1; 95% CI, 1.2 to 3.5), diabetes mellitus (RR=2.0; 95% CI, 1.2 to 3.3), and high-grade (>60% stenosis or occlusion) disease in either the ipsilateral (RR=1.9; 95% CI, 1.2 to 3.0) or contralateral (RR=1.7; 95% CI, 1.0 to 2.8) renal artery. CONCLUSIONS Although renal artery disease progression is a frequent occurrence, progression to total renal artery occlusion is not. The risk of renal artery disease progression is highest among individuals with preexisting high-grade stenosis in either renal artery, elevated systolic blood pressure, and diabetes mellitus.

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.

Biologic Prosthesis Reduces Recurrence After Laparoscopic Paraesophageal Hernia Repair: A Multicenter, Prospective, Randomized Trial

Objective:Laparoscopic paraesophageal hernia repair (LPEHR) is associated with a high recurrence rate. Repair with synthetic mesh lowers recurrence but can cause dysphagia and visceral erosions. This trial was designed to study the value of a biologic prosthesis, small intestinal submucosa (SIS), in LPEHR. Methods:Patients undergoing LPEHR (n = 108) at 4 institutions were randomized to primary repair −1° (n = 57) or primary repair buttressed with SIS (n = 51) using a standardized technique. The primary outcome measure was evidence of recurrent hernia (≥2 cm) on UGI, read by a study radiologist blinded to the randomization status, 6 months after operation. Results:At 6 months, 99 (93%) patients completed clinical symptomatic follow-up and 95 (90%) patients had an UGI. The groups had similar clinical presentations (symptom profile, quality of life, type and size of hernia, esophageal length, and BMI). Operative times (SIS 202 minutes vs. 1° 183 minutes, P = 0.15) and perioperative complications did not differ. There were no operations for recurrent hernia nor mesh-related complications. At 6 months, 4 patients (9%) developed a recurrent hernia >2 cm in the SIS group and 12 patients (24%) in the 1° group (P = 0.04). Both groups experienced a significant reduction in all measured symptoms (heartburn, regurgitation, dysphagia, chest pain, early satiety, and postprandial pain) and improved QOL (SF-36) after operation. There was no difference between groups in either pre or postoperative symptom severity. Patients with a recurrent hernia had more chest pain (2.7 vs. 1.0, P = 0.03) and early satiety (2.8 vs. 1.3, P = 0.02) and worse physical functioning (63 vs. 72, P = 0.03 per SF-36). Conclusions:Adding a biologic prosthesis during LPEHR reduces the likelihood of recurrence at 6 months, without mesh-related complications or side effects.