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Previous studies demonstrated that men were more likely to have plaque rupture and are at greater risk for myocardial infarction and stroke than women. We evaluated differences in carotid plaque characteristics by MRI between men and women with mild-moderate atherosclerosis and elevated ApoB levels. One hundred eighty-two subjects (104 men and 78 women) with CAD or carotid stenosis (≥ 15% by ultrasound), ApoB ≥ 120 mg/dL and carotid MRI scan were included. Percent wall volume (%WV) was calculated as (wall volume/total vessel volume) × 100%. Three major plaque compositions, fibrous tissue (FT), calcification (CA) and lipid rich necrotic core (LRNC), were identified and quantified using published MRI criteria. Adventitial and plaque neovascularization as fractional plasma volume (V p ) and permeability as transfer constant (K trans ) were analyzed using kinetic modeling. These characteristics were compared between men and women. Men, compared to women, were younger (54 ± 8 vs. 58 ± 8 years, p = 0.01), had higher rate of previous MI (46 vs. 26%, p = 0.005) but lower proportions of metabolic syndrome (37 vs. 59%, p = 0.003). After adjusting for between-gender differences, men were significantly more likely to have LRNC (OR 2.22, 95% CI 1.04-4.89, p = 0.04) and showed significantly larger %LRNC than women (diff = 4.3%, 95% CI 1.6-6.9%, p = 0.002), while %WV, FT, and CA were similar between men and women. There were no statistically significant differences in adventitial and plaque V p or K trans . Men were significantly more likely to have LRNC and had larger LRNC than women. However, men and women showed relatively similar levels of adventitial and plaque neovascularization and permeability.Trial registration: NCT00715273 at ClinicalTrials.gov. Registered 15 July 2008, retrospectively registered.

Objectives: The aim of this study was to investigate whether and what carotid plaque characteristics predict systemic cardiovascular outcomes in patients with clinically established atherosclerotic disease., Background: Advancements in atherosclerosis imaging have allowed assessment of various plaque characteristics, some of which are more directly linked to the pathogenesis of acute cardiovascular events compared to plaque burden., Methods: As part of the event-driven clinical trial AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes), subjects with clinically established atherosclerotic disease underwent multicontrast carotid magnetic resonance imaging (MRI) to detect plaque tissue composition and high-risk features. Prospective associations between MRI measurements and the AIM-HIGH primary endpoint (fatal and nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome, and symptom-driven revascularization) were analyzed using Cox proportional hazards survival models., Results: Of the 232 subjects recruited, 214 (92.2%) with diagnostic image quality constituted the study population (82% male, mean age 61 ± 9 years, 94% statin use). During median follow-up of 35.1 months, 18 subjects (8.4%) reached the AIM-HIGH endpoint. High lipid content (hazard ratio [HR] per 1 SD increase in percent lipid core volume: 1.57; p = 0.002) and thin/ruptured fibrous cap (HR: 4.31; p = 0.003) in carotid plaques were strongly associated with the AIM-HIGH endpoint. Intraplaque hemorrhage had a low prevalence (8%) and was marginally associated with the AIM-HIGH endpoint (HR: 3.00; p = 0.053). High calcification content (HR per 1 SD increase in percent calcification volume: 0.66; p = 0.20), plaque burden metrics, and clinical risk factors were not significantly associated with the AIM-HIGH endpoint. The associations between carotid plaque characteristics and the AIM-HIGH endpoint changed little after adjusting for clinical risk factors, plaque burden, or AIM-HIGH randomized treatment assignment., Conclusions: Among patients with clinically established atherosclerotic disease, carotid plaque lipid content and fibrous cap status were strongly associated with systemic cardiovascular outcomes. Markers of carotid plaque vulnerability may serve as novel surrogate markers for systemic atherothrombotic risk., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: Plaque neovasculature is a major route for lipoprotein and leukocyte ingress into plaques, and has been identified as a risk factor for carotid plaque disruption. Vp, a variable derived from pharmacokinetic modeling of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), correlates with plaque neovasculature density. Because lipid-lowering therapy has been associated with regression of neovasculature in animal models, we sought to determine clinical correlates of carotid plaque neovasculature (as assessed by Vp) in participants on statin therapy for established cardiovascular disease., Methods: 98 participants from an AIM-HIGH sub-study underwent DCE-MRI of their carotid arteries. Expert readers who were blinded to all clinical variables analyzed the MR images to measure carotid plaque Vp in all participants. Associations between Vp and duration of statin therapy and other clinical risk factors were analyzed., Results: Prior duration of statin treatment at enrollment ranged from <1 year (21%) 1-5 years (40%) and >5 years (39%). In univariate analyses, shorter duration of statin therapy (P = 0.01), the presence of metabolic syndrome (P = 0.02), and higher body mass index (P = 0.01) and lipoprotein(a) (P = 0.01) were all significantly associated with higher baseline Vp values. In multivariate analyses, significant associations remained between shorter duration of statin therapy (P = 0.004) and lipoprotein(a) (P = 0.04)., Conclusions: These are the first human, in vivo findings suggesting a relationship between duration of statin therapy and regression of carotid plaque neovasculature. Future longitudinal studies are warranted both to confirm this finding and to address whether changes in neovasculature may translate into change in risk for plaque disruption. CLINICALTRIALS., Gov Identifiers: NCT00880178, NCT01178320 and NCT00120289., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To investigate whether short-term, intensive lipid therapy leads to changes in microvascular characteristics, as measured by using dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging., Materials and Methods: Institutional review board approval and informed consent were obtained for this HIPAA-compatible study. Subjects with established coronary artery disease or carotid artery stenosis of 15% or greater determined by using ultrasonography and with levels of apolipoprotein B of 120 mg/dL (1.2 g/L) or greater were enrolled in an ongoing study (clinical trial NCT00715273). All received intensive lipid therapy to achieve targeted high- and low-density lipoprotein cholesterol levels and underwent serial serum monitoring including high-sensitivity C-reactive protein (HsCRP) level measurements. Carotid artery MR imaging examinations including morphologic and DCE MR images were obtained at baseline and 1 year after treatment. In subjects with advanced lesions (>2 mm thick), MR image analysis was performed, including measurement of lipid-rich necrotic core size and kinetic modeling of DCE MR images to assess changes in the transfer constant (K(trans)). The differences in K(trans) between baseline and 1-year follow-up were compared by using the Wilcoxon signed rank test, and associations were assessed by using the Spearman rank correlation coefficient., Results: Twenty-eight subjects with interpretable DCE MR imaging results at both baseline and 1-year follow-up were included. After 1 year of treatment, a significant reduction was found in mean K(trans) (0.085 min(-1) ± 0.037 [standard deviation] to 0.067 min(-1) ± 0.028, P = .02). Reduction in K(trans) was not significantly correlated with observed reductions in lipid-rich necrotic core size or reductions in HsCRP level., Conclusion: These findings suggest that DCE MR imaging may be a useful imaging method for the assessment of the therapeutic response of the vasa vasorum in patients with atherosclerotic plaque.

Purpose: To determine if better flow suppression can meaningfully improve the reproducibility of measurements associated with carotid atherosclerotic disease, particularly for lumen and wall areas., Materials and Methods: Eighteen subjects with carotid artery stenosis identified by duplex ultrasound (11 with 16%-49% stenosis; 7 with 50%-79% stenosis) underwent two carotid magnetic resonance imaging (MRI) examinations on a 3T scanner with a 4-channel phased array coil. High-resolution intermediate-weighted TSE (TR/TE = 4000/8.5 msec, 0.55 mm in-plane resolution, 2 mm slice thickness, 16 slices, 3-minute scan time) with two different flow-suppression techniques (multislice double inversion recovery [mDIR] and motion-sensitized driven-equilibrium [MSDE]) were obtained separately. For each subject, bilateral arteries were reviewed. One radiologist blinded to timepoints, flow suppression techniques, and clinical information measured the arterial lumen area, wall area, and total vessel wall area., Results: Compared to mDIR, the MSDE technique had a smaller interscan standard deviation (SD) in lumen (SD: 3.6 vs. 5.2 mm(2), P = 0.02), wall area measurements (SD: 4.5 vs. 6.4 mm(2), P = 0.02), and a trend towards smaller SD in total vessel area measurement (SD: 4.4 vs. 4.9 mm(2), P = 0.07)., Conclusion: The results from this study demonstrate that vessel wall imaging could quantify atherosclerotic plaque measurements more reliably with an improved blood suppression technique. This relationship between flow-suppression efficiency and reproducibility of plaque measurements is important, as more reliable area measurements will be useful in clinical diagnosis and in serial MRI studies that monitor carotid atherosclerotic lesion progression and regression., (2010 Wiley-Liss, Inc.)

Background The aim of this study is to investigate the inter-scan reproducibility of kinetic parameters in atherosclerotic plaque using dynamic contrast-enhanced (DCE) cardiovascular magnetic resonance (CMR) in a multi-center setting at 3T. Methods Carotid arteries of 51 subjects from 15 sites were scanned twice within two weeks on 3T scanners using a previously described DCE-CMR protocol. Imaging data with protocol compliance and sufficient image quality were analyzed to generate kinetic parameters of vessel wall, expressed as transfer constant (Ktrans) and plasma volume (vp). The inter-scan reproducibility was evaluated using intra-class correlation coefficient (ICC) and coefficient of variation (CV). Power analysis was carried out to provide sample size estimations for future prospective study. Results Ten (19.6%) subjects were found to suffer from protocol violation, and another 6 (11.8%) had poor image quality (n = 6) in at least one scan. In the 35 (68.6%) subjects with complete data, the ICCs of Ktrans and vp were 0.65 and 0.28, respectively. The CVs were 25% and 62%, respectively. The ICC and CV for vp improved to 0.73 and 28% in larger lesions with analyzed area larger than 25 mm2. Power analysis based on the measured CV showed that 50 subjects per arm are sufficient to detect a 20% difference in change of Ktrans over time between treatment arms with 80% power without consideration of the dropout rate. Conclusion The result of this study indicates that quantitative measurement from DCE-CMR is feasible to detect changes with a relatively modest sample size in a prospective multi-center study despite the limitations. The relative high dropout rate suggested the critical needs for intensive operator training, optimized imaging protocol, and strict quality control in future studies. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to test the lipid depletion hypothesis and to establish the time course of change in carotid plaque morphology and composition during lipid therapy using high-resolution magnetic resonance imaging (MRI). Background: Lipid therapy is thought to improve plaque stability and reduce cardiovascular events by targeting the plaque rupture risk features such as large lipid core, thin fibrous cap, and high level of inflammatory infiltrates. However, the plaque stabilizing process during lipid therapy has not been clearly demonstrated in humans and in vivo. Methods: Subjects with coronary or carotid artery disease, apolipoprotein B ≥120 mg/dl, and lipid treatment history <1 year, were randomly assigned to atorvastatin monotherapy or to atorvastatin-based combination therapies with appropriate placebos for 3 years. All subjects underwent high-resolution, multicontrast bilateral carotid MRI scans at baseline and annually for 3 years. All images were analyzed for quantification of wall area and plaque composition blinded to therapy, laboratory results, and clinical course. Results: After 3 years of lipid therapy, the 33 subjects with measurable lipid-rich necrotic core (LRNC) at baseline had a significant reduction in plaque lipid content: LRNC volume decreased from 60.4 ± 59.5 mm3 to 37.4 ± 69.5 mm3 (p < 0.001) and %LRNC (LRNC area/wall area in the lipid-rich regions) from 14.2 ± 7.0% to 7.4 ± 8.2% (p < 0.001). The time course showed that %LRNC decreased by 3.2 (p < 0.001) in the first year, by 3.0 (p = 0.005) in the second year, and by 0.91 (p = 0.2) in the third year. Changes in LRNC volume followed the same pattern. Percent wall volume (100 × wall/outer wall, a ratio of volumes) in the lipid-rich regions significantly decreased from 52.3 ± 8.5% to 48.6 ± 9.7% (p = 0.002). Slices containing LRNC had significantly more percent wall volume reduction than those without (−4.7% vs. −1.4%, p = 0.02). Conclusions: Intensive lipid therapy significantly depletes carotid plaque lipid. Statistically significant plaque lipid depletion is observed after 1 year of treatment and continues in the second year, and precedes plaque regression. (Using Magnetic Resonance Imaging to Evaluate Carotid Artery Plaque Composition in People Receiving Cholesterol-Lowering Medications [The CPC Study]; NCT00715273). [Copyright &y& Elsevier]

Background: Previous studies indicate that isolated posterior cruciate ligament injuries demonstrate magnetic resonance imaging (MRI) and clinical evidence of healing when treated nonoperatively; however, the authors are unaware of any other study that has looked at whether initial MRI can predict posterior cruciate ligament stability at the time of surgery in patients with knee dislocation.Hypothesis: An MRI grading system will predict laxity on posterior drawer testing at the time of surgery in patients with knee dislocations.Study Design: Cohort study (prognosis); Level of evidence, 2.Methods: Forty-two consecutive patients with knee dislocation or multiple-ligament knee injury evaluated by MRI were included in the study. An assignment of grade 0 (intact), grade I (injured/fibers intact), grade II (partial tearing of ligament), or grade III (complete tear) was made after each reading on 2 separate occasions by 3 surgeons. Posterior laxity of the knee was graded by the magnitude of excursion on the posterior drawer test by the senior author at the time of surgery. Interobserver and intraobserver reliability of the MRI grading scheme expressed by the kappa statistic κ, as well as the predictive value of MRI grade in determining stability of the posterior cruciate ligament at the time of surgery, was assessed.Results: The posterior cruciate ligament injury grading scheme tested demonstrated moderate to substantial intraobserver agreement (κ = 0.66, κ = 0.53, and κ = 0.52, respectively, for all raters). Interobserver reliability demonstrated only moderate agreement (κ = 0.49). If the grading scheme was changed to group both grades 0 and I (intact) and grades II and III (disrupted), intraobserver reliability demonstrated substantial to almost perfect agreement (κ = 0.83, κ = 0.80, and κ = 0.75), and interobserver reliability demonstrated substantial agreement (κ = 0.70). If the posterior cruciate ligament was classified as intact (grade 0 [intact] or grade I [injured]) on initial MRI, the injured knee was judged clinically stable (tibia anterior to or flush with the femoral condyles on posterior drawer testing) at the time of surgery 98.5% (95% confidence interval, 93%-100%) of the time. When the posterior cruciate ligament was classified as disrupted (grade II [partial tear] or grade III [complete tear]), the injured knee was judged unstable (tibia posterior to the femoral condyles on posterior drawer testing) 57.5% (95% confidence interval, 40%-73%) of the time.Conclusion: The presented system of grading posterior cruciate ligament injury in patients with knee dislocation on initial MRI demonstrates moderate to substantial interobserver and intraobserver reliability that increases if the grading scheme is modified. An initial MRI scan read as grade I may predict stability to posterior drawer at the time of surgery. Even with MRI evidence of disruption in the posterior cruciate ligament (grade II and grade III injuries), posterior cruciate ligament reconstruction may not be clinically indicated at the time of reconstruction and/or repair of other associated injuries. [ABSTRACT FROM AUTHOR]