Plaque Evolution and Vessel Wall Remodeling of Intracranial Arteries: A Prospective, Longitudinal Vessel Wall MRI Study.

BACKGROUND: Progression of intracranial atherosclerotic disease (ICAD) is associated with ischemic stroke events and can be quantified with three-dimensional (3D) intracranial vessel wall (IVW) MRI. However, longitudinal 3D IVW studies are limited and ICAD evolution remains relatively unknown. PURPOSE: To evaluate ICAD changes longitudinally and to characterize the imaging patterns of atherosclerotic plaque evolution. STUDY TYPE: Prospective. POPULATION: 37 patients (69 ± 12 years old, 12 females) with angiography confirmed ICAD. FIELD STRENGTH/SEQUENCE: 3.0T/3D time-of-flight gradient echo sequence and T1- and proton density-weighted fast spin echo sequences. ASSESSMENT: Each patient underwent baseline and 1-year follow-up IVW. Then, IVW data from both time points were jointly preprocessed using a multitime point, multicontrast, and multiplanar viewing workflow (known as MOCHA). Lumen and outer wall of plaques were traced and measured, and plaques were then categorized into progression, stable, and regression groups based on changes in plaque wall thickness. Patient demographic and clinical data were collected. Culprit plaques were identified based on cerebral ischemic infarcts. STATISTICAL TESTS: Generalized estimating equations-based linear and logistic regressions were used to assess associations between vascular risk factors, medications, luminal stenosis, IVW plaque imaging features, and longitudinal changes. A two-sided P-value<0.05 was considered statistically significant. RESULTS: Diabetes was significantly associated with ICAD progression, resulting in 6.6% decrease in lumen area and 6.7% increase in wall thickness at 1-year follow-up. After accounting for arterial segments, baseline contrast enhancement predicted plaque progression (odds ratio = 3.61). Culprit plaques experienced an average luminal expansion of 10.9% after 1 year. 74% of the plaques remained stable during follow-up. The regression group (18 plaques) showed significant increase in minimum lumen area (from 7.4 to 8.3 mm2 ), while the progression group (13 plaques) showed significant decrease in minimum lumen area (from 5.4 to 4.3 mm2 ). DATA CONCLUSION: Longitudinal 3D IVW showed ICAD remodeling on the lumen side. Culprit plaques demonstrated longitudinal luminal expansion compared with their non-culprit counterparts. Baseline plaque contrast enhancement and diabetes mellitus were found to be significantly associated with ICAD changes. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Alterations in cerebral distal vascular features and effect on cognition in a high cardiovascular risk population: A prospective longitudinal study.

BACKGROUND: Alterations in cerebral vasculature are instrumental in affecting cognition. Current studies mainly focus on proximal large arteries and small vessels, while disregarding morphology and blood flow of the arteries between them (medium-to-large arteries). METHODS: In this prospective study, two types of non-contrast enhanced magnetic resonance angiography (NCE-MRA) techniques, simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP) and 3D Time-of-flight (TOF), were used to measure vascular morphologic features in medium-to-large intracranial arteries. Grey matter (GM) tissue level perfusion was assessed with arterial spin labeling (ASL) MRI. Twenty-seven subjects at high cardiovascular risk underwent baseline and 12-month follow-up MRI to compare the relationship between morphological features measured by NCE MRA, GM CBF by ASL MRI, and cognitive function measured by the Montreal Cognitive Assessment (MoCA). RESULTS: Changes in both global medium-to-large arteries and posterior cerebral (PCA) distal artery length and branch numbers, measured on SNAP MRA, were significantly associated with alterations in MoCA scores (P < 0.01), after adjusting for clinical confounding factors, total brain volume, and total white matter lesion (WML) volume. There were no associations between MoCA scores and vascular features on TOF MRA or ASL GM CBF. CONCLUSIONS: Alterations in vascular features of distal medium-to-large arteries may be more sensitive for detecting potential changes in cognition than cerebral blood flow alterations at the parenchymal level captured by perfusion ASL. Hemodynamic information from distal medium-to-large arteries provides an additional tool to advance understanding of the vascular contributions to cognitive function.

Magnetic Resonance Imaging of Intraplaque Hemorrhage and Plaque Lipid Content With Continued Lipid-Lowering Therapy: Results of a Magnetic Resonance Imaging Substudy in AIM-HIGH.

BACKGROUND: Intraplaque hemorrhage (IPH) is associated with plaque progression and ischemic events, and plaque lipid content (% lipid core) predicts the residual atherosclerotic cardiovascular disease risk. This study examined the impact of IPH on lipid content change in the setting of intensive lipid-lowering therapy. METHODS: In total, 214 AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low High-Density Lipoprotein/High Triglycerides: Impact on Global Health Outcomes) participants with clinically established ASCVD and low high-density lipoprotein cholesterol received cartoid MRI at baseline and 2 years to assess changes in carotid morphology and composition. Patients were randomized to extended-release niacin or placebo, and all received simvastatin with optional ezetimibe as necessary to lower low-density lipoprotein cholesterol to 40 to 80 mg/dL. Changes in lipid content and carotid morphology were tested using the Wilcoxon signed-rank test. Differences between subjects with and without IPH and between subjects assigned extended-release niacin or placebo were tested using the Wilcoxon rank-sum test. Linear regression was used to test the association of IPH and lipid content changes after adjusting for clinical risk factors. RESULTS: Among 156 patients (61±9 years; 81% men) with complete MRI, prior statin use: <1 year, 26%; 1 to 5 years, 37%; >5 years, 37%. Triglycerides and ApoB decreased significantly, whereas high-density lipoprotein cholesterol and ApoA1 increased significantly over time. Plaque lipid content was significantly reduced (-0.5±2.4 %/year, P = 0.017) without a significant difference between the 2 treatment groups. However, the lipid content increased in plaques with IPH but regressed in plaques without IPH (1.2±2.5 %/year versus -1.0±2.2, P = 0.006). Additionally, IPH was associated with a decrease in lumen area (-0.4±0.9 mm2/year versus 0.3±1.4, P = 0.033). IPH remained significantly associated with increase in lipid content in multivariable analysis (54.4%, 95% CI: 26.8, 88.0, P < 0.001). CONCLUSIONS: Carotid plaques under continued intensive lipid-lowering therapy moved toward stabilization. However, plaques with IPH showed greater increases in lipid content and greater decreases in lumen area than plaques without IPH. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01178320.

Characterization of non-stenotic plaques in intracranial arteries with multi-contrast, multi-planar vessel wall image analysis.

OBJECTIVES: Non-stenotic plaques have been observed in intracranial arteries but are less understood compared to those in coronary and carotid arteries. We sought to compare plaque distribution and morphology between stenotic and non-stenotic intracranial plaques with MR vessel wall imaging (VWI) and quantitative image analysis. MATERIALS AND METHODS: Twenty-four patients with intracranial arterial stenosis or luminal irregularity on clinical imaging were scanned with a multi-contrast VWI protocol. Plaques were detected as focal wall thickening on co-registered multiplanar reformats of multi-contrast VWI, with assessment of the location and morphology. TOF-MRA was independently reviewed for any appreciable stenosis using the WAISD criteria. RESULTS: Across 504 arterial segments, a total of 80 plaques were detected, including 23 (29%) with stenosis on TOF-MRA, 56 (70%) without, and 1 (1%) not covered by TOF-MRA. Plaques involving the ICA were more likely to be non-stenotic than those involving other segments (80% versus 55%, p = 0.030) whereas the basilar artery (40%) and PCA (33%) had the lowest proportions of non-stenotic plaques. Maximum wall thickness, indicative of plaque burden, correlated poorly with degree of stenosis (p = 0.10) and overlapped substantially between stenotic and non-stenotic plaques (1.9 [1.5, 2.4] versus 2.0 [1.5, 2.2] mm, p = 0.074). CONCLUSIONS: Intracranial plaques without appreciable stenosis on TOF-MRA represent a large proportion of lesions throughout arterial segments but disproportionately affect the ICA. Morphological characterization of plaques with and without stenosis shows that luminal stenosis is a poor indicator of the underlying burden of intracranial atherosclerosis.

Associations of intracranial artery length and branch number on non-contrast enhanced MRA with cognitive impairment in individuals with carotid atherosclerosis.

Developing novel risk markers for vascular contributions to cognitive impairment and dementia is important. This study aimed to extract total length, branch number and average tortuosity of intracranial distal arteries (A2, M2, P2 and more distal) from non-contrast enhanced magnetic resonance angiography (NCE-MRA) images, and explore their associations with global cognition. In 29 subjects (aged 40-90 years) with carotid atherosclerotic disease, the 3 intracranial vascular features on two NCE-MRA techniques (i.e. time of flight, TOF and simultaneous non-contrast angiography and intraplaque hemorrhage, SNAP) were extracted using a custom-developed software named iCafe. Arterial spin labeling (ASL) and phase contrast (PC) cerebral blood flow (CBF) were measured as references. Linear regression was performed to study their associations with global cognition, measured with the Montreal Cognitive Assessment (MoCA). Intracranial artery length and number of branches on NCE-MRA, ASL CBF and PC CBF were found to be positively associated with MoCA scores (P < 0.01). The associations remained significant for artery length and number of branches on NCE-MRA after adjusting for clinical covariates and white matter hyperintensity volume. Further adjustment of confounding factors of ASL CBF or PC CBF did not abolish the significant association for artery length and number of branches on TOF. Our findings suggest that intracranial vascular features, including artery length and number of branches, on NCE-MRA may be useful markers of cerebrovascular health and provide added information over conventional brain blood flow measurements in individuals with cognitive impairment.

Multi-Planar, Multi-Contrast and Multi-Time Point Analysis Tool (MOCHA) for Intracranial Vessel Wall Characterization.

BACKGROUND: Three-dimensional (3D) intracranial vessel wall (IVW) magnetic resonance imaging can reliably image intracranial atherosclerotic disease (ICAD). However, an integrated, streamlined, and optimized workflow for IVW analysis to provide qualitative and quantitative measurements is lacking. PURPOSE: To propose and evaluate an image analysis pipeline (MOCHA) that can register multicontrast and multitime point 3D IVW for multiplanar review and quantitative plaque characterization. STUDY TYPE: Retrospective. POPULATION: A total of 11 subjects with ICAD (68 ± 10 years old, 6 males). FIELD STRENGTH/SEQUENCE: A 3.0 T, 3D time-of-flight gradient echo sequence and T1- and proton density-weighted fast spin echo sequences. ASSESSMENT: Each participant underwent two IVW sessions within 2 weeks. Scan and rescan IVW images were preprocessed using MOCHA. The presence of atherosclerotic lesions was identified in different intracranial arterial segments by two readers (GC and JS, 12 years of vascular MR imaging experience each) following an established review protocol to reach consensus on each of the reviews. For all locations with identified plaques, plaque length, lumen and vessel wall areas, maximum and mean wall thickness values, normalized wall index and contrast enhancement ratio were measured. STATISTICAL TESTS: Percent agreement and Cohen's κ were used to test scan-rescan reproducibility of detecting plaques using MOCHA. Intraclass correlation coefficient (ICC) and Bland-Altman analysis were used to evaluate scan-rescan reproducibility for plaque morphologic and enhancement measurements. RESULTS: In 150 paired intracranial vessel segments, the overall agreement in plaque detection was 92.7% (κ = 0.822). The ICCs (all ICCs > 0.90) and Bland-Altman plots (no bias observed) indicated excellent scan-rescan reproducibility for all morphologic and enhancement measurements. DATA CONCLUSION: Findings from this study demonstrate that MOCHA provides high scan-rescan reproducibility for identification and quantification of atherosclerosis along multiple intracranial arterial segments and highlight its potential use in characterizing plaque composition and monitoring plaque development. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Atherosclerotic Burden and Remodeling Patterns of the Popliteal Artery as Detected in the Magnetic Resonance Imaging Osteoarthritis Initiative Data Set.

Background An artificial intelligence vessel segmentation tool, Fully Automated and Robust Analysis Technique for Popliteal Artery Evaluation (FRAPPE), was used to analyze a large databank of popliteal arteries imaged through the OAI (Osteoarthritis Initiative) to study the impact of atherosclerosis risk factors on vessel dimensions and characterize remodeling patterns. Methods and Results Magnetic resonance images from 4668 subjects contributing 9189 popliteal arteries were analyzed using FRAPPE. Age ranged from 45 to 79 years (median, 61), and 58% were women. Mean lumen diameter, mean outer wall diameter, and mean wall thickness (MWT) were measured per artery. Their median values were 5.8 mm (interquartile range, 5.2-6.5 mm), 7.3 mm (interquartile range, 6.7-8.1 mm), and 0.78 mm (interquartile range, 0.73-0.84 mm) respectively. MWT was associated with multiple cardiovascular risk factors, with age (4.2% increase in MWT per 10-year increase in age; 95% CI, 3.9%-4.5%) and sex (8.6% higher MWT in men than women; 95% CI, 7.7%-9.3%) being predominant. On average, lumen and outer wall diameters increased with increasing MWT until the thickness was 0.92 mm for men and 0.84 mm for women. After this point, lumen diameter decreased steadily, more rapidly in men than women (-7.9% versus -6.1% per 25% increase in MWT; P<0.001), with little change in outer wall diameter. Conclusions FRAPPE has enabled the analysis of the large OAI knee magnetic resonance imaging data set, successfully showing that popliteal atherosclerosis is predominantly associated with age and sex. The average vessel remodeling pattern consisted of an early phase of compensatory enlargement, followed by a negative remodeling, which is more pronounced in men.

Regression in carotid plaque lipid content and neovasculature with PCSK9 inhibition: A time course study.

BACKGROUND AND AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce cardiovascular events, but their effects on atherosclerotic plaque remain elusive. Using serial magnetic resonance imaging (MRI), we studied changes in carotid plaque lipid content and neovasculature under PCSK9 inhibition with alirocumab. METHODS: Among patients with low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dl but ineligible for high-dose statin therapy, those with lipid core on carotid MRI were identified to receive alirocumab 150 mg every 2 weeks. Follow-up MRI was performed at 3, 6, and 12 months after treatment. Pre- and post-contrast MRI were acquired to measure percent lipid core volume (% lipid core). Dynamic contrast-enhanced MRI was acquired to measure the extravasation rate of gadolinium contrast (Ktrans), a marker of plaque neovasculature. RESULTS: Of 31 patients enrolled, 27 completed the study (mean age: 69 ± 9; male: 67%). From 9.8% at baseline, % lipid core was progressively reduced to 8.4% at 3 months, 7.5% at 6 months, and 7.2% at 12 months (p = 0.014 for trend), which was accompanied by a progressive increase in % fibrous tissue (p = 0.009) but not % calcification (p = 0.35). Ktrans was not reduced until 12 months (from 0.069 ± 0.019 min-1 to 0.058 ± 0.020 min-1; p = 0.029). Lumen and wall areas did not change significantly during the study period. CONCLUSIONS: Regression in plaque composition and neovasculature were observed under PCSK9 inhibition on carotid MRI, which provides unique insight into the biological process of plaque stabilization with disease-modifying therapies.

Vessel length on SNAP MRA and TOF MRA is a potential imaging biomarker for brain blood flow.

PURPOSE: To explore feasibility of using the vessel length on time-of-flight (TOF) or simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP) MRA as an imaging biomarker for brain blood flow, by using arterial spin labeling (ASL) perfusion imaging and 3D phase contrast (PC) quantitative flow imaging as references. METHODS: In a population of thirty subjects with carotid atherosclerotic disease, the visible intracranial arteries on TOF and SNAP were semi-automatically traced and the total length of the distal segments was calculated with a dedicated software named iCafe. ASL blood flow was calculated automatically using the recommended hemodynamic model. PC blood flow was obtained by generating cross-sectional arterial images and semi-automatically drawing the lumen contours. Pearson correlation coefficients were used to assess the associations between the different whole-brain or hemispheric blood flow measurements. RESULTS: Under the imaging protocol used in this study, TOF vessel length was larger than SNAP vessel length (P < 0.001). Both whole-brain TOF and SNAP vessel length showed a correlation with whole brain ASL and 3D PC blood flow measurements, and the correlation coefficients were higher for SNAP vessel length (TOF vs ASL: R = 0.554, P = 0.002; SNAP vs ASL: R = 0.711, P < 0.001; TOF vs 3D PC: R = 0.358, P = 0.052; SNAP vs 3D PC: R = 0.425, P = 0.019). Similar correlation results were observed for the hemispheric measurements. Hemispheric asymmetry index of SNAP vessel length also showed a significant correlation with hemispheric asymmetry index of ASL cerebral blood flow (R = 0.770, P < 0.001). CONCLUSION: The results suggest that length of the visible intracranial arteries on TOF or SNAP MRA can serve as a potential imaging marker for brain blood flow.

Chronic kidney disease, atherosclerotic plaque characteristics on carotid magnetic resonance imaging, and cardiovascular outcomes.

BACKGROUND: It is unclear whether faster progression of atherosclerosis explains the higher risk of cardiovascular events in CKD. The objectives of this study were to 1. Characterize the associations of CKD with presence and morphology of atherosclerotic plaques on carotid magnetic resonance imaging (MRI) and 2. Examine the associations of baseline CKD and carotid atherosclerotic plaques with subsequent cardiovascular events. METHODS: In a subgroup (N = 465) of Systolic Blood Pressure Intervention Trial. (SPRINT) participants, we measured carotid plaque presence and morphology at baseline and after 30-months with MRI. We examined the associations of CKD (baseline eGFR < 60 ml/min/1.73m2) with progression of carotid plaques and the SPRINT cardiovascular endpoint. RESULTS: One hundred and ninety six (42%) participants had CKD. Baseline eGFR in the non-CKD and CKD subgroups were 77 ± 14 and 49 ± 8 ml/min/1.73 m2, respectively. Lipid rich necrotic-core plaque was present in 137 (29.5%) participants. In 323 participants with both baseline and follow-up MRI measurements of maximum wall thickness, CKD was not associated with progression of maximum wall thickness (OR 0.62, 95% CI 0.36 to 1.07, p = 0.082). In 96 participants with necrotic core plaque at baseline and with a valid follow-up MRI, CKD was associated with lower odds of progression of necrotic core plaque (OR 0.41, 95% CI 0.17 to 0.95, p = 0.039). There were 28 cardiovascular events over 1764 person-years of follow-up. In separate Cox models, necrotic core plaque (HR 2.59, 95% CI 1.15 to 5.85) but not plaque defined by maximum wall thickness or presence of a plaque component (HR 1.79, 95% CI 0.73 to 4.43) was associated with cardiovascular events. Independent of necrotic core plaque, CKD (HR 3.35, 95% CI 1.40 to 7.99) was associated with cardiovascular events. CONCLUSIONS: Presence of necrotic core in carotid plaque rather than the presence of plaque per se was associated with increased risk of cardiovascular events. We did not find CKD to be associated with faster progression of necrotic core plaques, although both were independently associated with cardiovascular events. Thus, CKD may contribute to cardiovascular disease principally via mechanisms other than atherosclerosis such as arterial media calcification or stiffening. TRIAL REGISTRATION: NCT01475747 , registered on November 21, 2011.

Serial magnetic resonance imaging detects a rapid reduction in plaque lipid content under PCSK9 inhibition with alirocumab.

PCSK9 inhibitors lower low-density lipoprotein cholesterol (LDL-C) and reduce cardiovascular events. The clinical benefits presumably result from favorable effects on atherosclerotic plaques. Lipid-core and plaque inflammation have been recognized as main determinants of risk for plaque rupture and cardiovascular events. Both can be noninvasively assessed with carotid MRI. We studied if PCSK9 inhibition with alirocumab induces regression in lipid-core or plaque inflammation within 6 months as measured by MRI. Patients with non-calcified carotid plaque(s) and baseline LDL-C ≥ 70 mg/dl, who were statin-intolerant or taking a low-dose statin (≤ 10 mg per day of atorvastatin or an equivalent), received subcutaneous alirocumab 150 mg every 2 weeks. Carotid MRI was performed at baseline and 6 months after treatment, including pre- and post-contrast images for measuring percent lipid-core volume (%LC) and dynamic contrast-enhanced images for measuring microvessel leakiness (Ktrans), a marker of inflammation. Twenty-eight patients completed the study (69 ± 9 years; 64% male). Alirocumab led to significant changes in LDL-C (p < 0.001) and high-density lipoprotein cholesterol (HDL-C) (p = 0.003). At 6 months, there was a significant reduction in %LC (mean: - 2.1% [- 3.5, - 0.7], p = 0.005; a 17% reduction from baseline of 9.9%) without significant changes in lumen/wall area or in the inflammatory index Ktrans. Carotid plaque lipid content was reduced by 17% after 6 months of PCSK9 inhibition with alirocumab. This was seen before observable changes in lumen or wall areas, which supports pursing plaque lipid content as a more sensitive marker of therapeutic response compared to lumen or wall areas in future technical developments and serial studies.

Fully automated and robust analysis technique for popliteal artery vessel wall evaluation (FRAPPE) using neural network models from standardized knee MRI.

PURPOSE: To develop a fully automated vessel wall (VW) analysis workflow (fully automated and robust analysis technique for popliteal artery evaluation, FRAPPE) on the popliteal artery in standardized knee MR images. METHODS: Popliteal artery locations were detected from each MR slice by a deep neural network model and connected into a 3D artery centerline. Vessel wall regions around the centerline were then segmented using another neural network model for segmentation in polar coordinate system. Contours from vessel wall segmentations were used for vascular feature calculation, such as mean wall thickness and wall area. A transfer learning and active learning framework was applied in training the localization and segmentation neural network models to maintain accuracy while reducing manual annotations. This new popliteal artery analysis technique (FRAPPE) was validated against manual segmentation qualitatively and quantitatively in a series of 225 cases from the Osteoarthritis Initiative (OAI) dataset. RESULTS: FRAPPE demonstrated high accuracy and robustness in locating popliteal arteries, segmenting artery walls, and quantifying arterial features. Qualitative evaluations showed 1.2% of slices had noticeable major errors, including segmenting the wrong target and irregular vessel wall contours. The mean Dice similarity coefficient with manual segmentation was 0.79, which is comparable to inter-rater variations. Repeatability evaluations show most of the vascular features have good to excellent repeatability from repeated scans of same subjects, with intra-class coefficient ranging from 0.80 to 0.98. CONCLUSION: This technique can be used in large population-based studies, such as OAI, to efficiently assess the burden of atherosclerosis from routine MR knee scans.

Evaluation of 3D multi-contrast carotid vessel wall MRI: a comparative study.

BACKGROUND: Conventional reference multi-contrast black-blood (BB) MRI can be used for measuring luminal stenosis severity and plaque components, and its performance has been validated by intra- and inter-reader reproducibility test and histology. Recently, a set of 3D multi-contrast BB sequences have been developed, but its accuracy and reliability have not been well investigated. In this study, we evaluated the performance of 3D multi-contrast MRI (3D-MERGE, T2-VISTA, and SNAP) by comparing it with reference multi-contrast vessel wall MRI and assessing the inter-reader reproducibility. METHODS: In total, 27 patients were recruited in this study. Twenty-six participants underwent reference and 3D multi-contrast imaging in a 3.0T MR scanner. One participant underwent carotid endarterectomy (CEA) after 3D MR imaging. Two trained reviewers interpreted reference and 3D datasets. Lumen area (LA), wall area (WA), normalized wall index (NWI), maximum wall thickness (MaxWT), and mean wall thickness (MWT) were measured, and the presence of lipid-rich necrotic core (LRNC), intra-plaque hemorrhage (IPH) and calcification (CA) were identified. Inter-reader reproducibility of 3D interpretation was assessed. RESULTS: 3D imaging provided comparable measurements with reference imaging in LA (43.81±25.74 vs. 43.35±24.66 mm2) and MaxWT (1.65±1.33 vs. 1.62±1.10 mm), with a lower NWI (0.40±0.15 vs. 0.43±0.11), WA (29.40±21.92 vs. 30.64±16.17 mm2) and MWT (1.09±0.69 vs. 1.14±0.47), and showed good agreement for identification of LRNC (κ=0.66, 95% CI: 0.30-1.00) and CA (κ=0.69, 95% CI: 0.42-0.97), and excellent agreement for IPH (κ=1.00, 95% CI: 1.00-1.00). Inter-reader agreement of 3D analysis was good (LRNC, κ=0.87, 95% CI: 0.61-1.00; CA, κ=0.66, 95% CI: 0.36-0.96; IPH, κ=1.00, 95% CI: 1.00-1.00). CONCLUSIONS: 3D multi-contrast vessel wall imaging provides comparable performance in morphological measurements and identification of carotid plaque components as reference multi-contrast MRI, with good inter-reader reproducibility.

Automated Artery Localization and Vessel Wall Segmentation using Tracklet Refinement and Polar Conversion.

Quantitative analysis of blood vessel wall structures is important to study atherosclerotic diseases and assess cardiovascular event risks. To achieve this, accurate identification of vessel luminal and outer wall contours is needed. Computer-assisted tools exist, but manual preprocessing steps, such as region of interest identification and/or boundary initialization, are still needed. In addition, prior knowledge of the ring shape of vessel walls has not been fully explored in designing segmentation methods. In this work, a fully automated artery localization and vessel wall segmentation system is proposed. A tracklet refinement algorithm was adapted to robustly identify the artery of interest from a neural network-based artery centerline identification architecture. Image patches were extracted from the centerlines and converted in a polar coordinate system for vessel wall segmentation. The segmentation method used 3D polar information and overcame problems such as contour discontinuity, complex vessel geometry, and interference from neighboring vessels. Verified by a large (>32000 images) carotid artery dataset collected from multiple sites, the proposed system was shown to better automatically segment the vessel wall than traditional vessel wall segmentation methods or standard convolutional neural network approaches. In addition, a segmentation uncertainty score was estimated to effectively identify slices likely to have errors and prompt manual confirmation of the segmentation. This robust vessel wall segmentation system has applications in different vascular beds and will facilitate vessel wall feature extraction and cardiovascular risk assessment.

Four Different Carotid Atherosclerotic Behaviors Based on Luminal Stenosis and Plaque Characteristics in Symptomatic Patients: An in Vivo Study.

Correct stratification of ischemic stroke risk allows for the proper treatment of carotid atherosclerotic disease. We seek to differentiate plaque types based on stenosis level and plaque morphology. The Chinese Atherosclerosis Risk Evaluation (CARE-II) study is a cross-sectional, observational, multicenter study to assess carotid atherosclerotic plaques in symptomatic subjects using vessel wall magnetic resonance imaging. Plaque morphology and presence of plaque components were reviewed using multi-contrast magnetic resonance imaging. The carotid arteries were divided into four groups based on stenosis level and plaque components. Out of 1072 ischemic stroke subjects, 452 ipsilateral side carotid arteries were included. Significant stenosis (SS) (≥50% stenosis) with high-risk plaque (HRP) features was present in 37 arteries (8.2%), SS(+)/HRP(-) in 29 arteries (6.4%), SS(-)/HRP(+) in 57 arteries (12.6%), and SS(-)/HRP(-) in 329 arteries (72.8%). The prevalence of SS(-)/HRP(+) arteries in this cohort was substantial and had greater wall thickness than the SS(+)/HRP(-) group. These arteries may be misclassified for carotid revascularization by current guidelines based on the degree of luminal stenosis only. These findings have implications for further studies to assess stroke risk using vessel wall imaging.

Combining morphological and biomechanical factors for optimal carotid plaque progression prediction: An MRI-based follow-up study using 3D thin-layer models.

Plaque progression prediction is of fundamental significance to cardiovascular research and disease diagnosis, prevention, and treatment. Magnetic resonance image (MRI) data of carotid atherosclerotic plaques were acquired from 20 patients with consent obtained. 3D thin-layer models were constructed to calculate plaque stress and strain. Data for ten morphological and biomechanical risk factors were extracted for analysis. Wall thickness increase (WTI), plaque burden increase (PBI) and plaque area increase (PAI) were chosen as three measures for plaque progression. Generalized linear mixed models (GLMM) with 5-fold cross-validation strategy were used to calculate prediction accuracy and identify optimal predictor. The optimal predictor for PBI was the combination of lumen area (LA), plaque area (PA), lipid percent (LP), wall thickness (WT), maximum plaque wall stress (MPWS) and maximum plaque wall strain (MPWSn) with prediction accuracy = 1.4146 (area under the receiver operating characteristic curve (AUC) value is 0.7158), while PA, plaque burden (PB), WT, LP, minimum cap thickness, MPWS and MPWSn was the best for WTI (accuracy = 1.3140, AUC = 0.6552), and a combination of PA, PB, WT, MPWS, MPWSn and average plaque wall strain (APWSn) was the best for PAI with prediction accuracy = 1.3025 (AUC = 0.6657). The combinational predictors improved prediction accuracy by 9.95%, 4.01% and 1.96% over the best single predictors for PAI, PBI and WTI (AUC values improved by 9.78%, 9.45%, and 2.14%), respectively. This suggests that combining both morphological and biomechanical risk factors could lead to better patient screening strategies.

Differences in Carotid Plaques Between Symptomatic Patients With and Without Diabetes Mellitus.

Objective- Diabetes mellitus is associated with high-risk atherosclerotic plaques. This study aimed to compare characteristics of carotid atherosclerotic plaques in symptomatic Chinese diabetic and nondiabetic patients using vessel wall magnetic resonance imaging. Approach and Results- Patients with cerebral ischemic symptoms in the anterior circulation and carotid atherosclerotic plaque determined by ultrasound were recruited from a cross-sectional, observational, multicenter study of CARE-II (Chinese Atherosclerosis Risk Evaluation). All patients underwent magnetic resonance imaging for carotid arteries. The morphological and compositional characteristics of carotid plaques were compared between diabetic and nondiabetic patients using linear (continuous variables) and logistic regression (binary variables). In a total of 584 recruited patients, 182 (31.2%) had diabetes mellitus. From the univariate analysis, diabetic patients had significantly greater mean wall area (33.7 versus 31.1 mm2; P=0.002), maximum wall thickness (3.2 versus 2.8 mm; P<0.001), and mean normalized wall index (43.8% versus 41.0%; P<0.001) and had significantly higher prevalence of calcification (51.6% versus 36.6%; P=0.001), lipid-rich necrotic core (77.5% versus 58.5%; P<0.001), and high-risk plaque (29.7% versus 19.9%; P=0.011) than nondiabetic patients. After adjusting for clinical characteristics, the differences in presence of calcification ( P=0.018) and lipid-rich necrotic core ( P=0.001) remained statistically significant. Conclusions- Symptomatic Chinese diabetic patients are more likely to have carotid plaques with calcification and lipid-rich necrotic core than nondiabetic patients, suggesting that diabetic patients may develop more severe atherosclerotic disease that should be accounted for in their clinical management.

Understanding Atherosclerosis Through an Osteoarthritis Data Set.

Atherosclerotic cardiovascular disease remains a worldwide epidemic and one of the leading causes of death nowadays. Vessel wall imaging can be used to understand the development and progression of atherosclerosis, but it is rarely done because of the high cost. We recently identified the Osteoarthritis Initiative, a large prospective cohort study of knee osteoarthritis, which might serve as a valuable source for atherosclerosis research with its serial knee magnetic resonance imaging data. We have found that these images are suitable for vessel wall image analysis of the lower extremity arteries. Here, we will introduce the Osteoarthritis Initiative data set and explain why it could be used for cardiovascular research purposes. Also, we will briefly comment on peripheral artery atherosclerosis as it is covered in the Osteoarthritis Initiative image data set and review the use of vessel wall imaging for studying atherosclerosis. We think data mining of imaging studies, not originally designed on cardiovascular research, can not only maximize the value of the imaging data set but also boost our understanding of atherosclerosis.