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Background and Purpose: Intracranial atherosclerosis is one of the main causes of stroke, and high-resolution magnetic resonance imaging provides useful imaging biomarkers related to the risk of ischemic events. This study aims to evaluate differences in histogram features between culprit and nonculprit intracranial atherosclerosis using high-resolution magnetic resonance imaging. Methods: Two hundred forty-seven patients with intracranial atherosclerosis who underwent high-resolution magnetic resonance imaging sequentially between January 2015 and December 2016 were recruited. Quantitative features, including stenosis, plaque burden, minimum luminal area, intraplaque hemorrhage, enhancement ratio, and dispersion of signal intensity (coefficient of variation), were analyzed based on T2-, T1-, and contrast-enhanced T1-weighted images. Step-wise regression analysis was used to identify key determinates differentiating culprit and nonculprit plaques and to calculate the odds ratios (ORs) with 95% CIs. Results: In total, 190 plaques were identified, of which 88 plaques (37 culprit and 51 nonculprit) were located in the middle cerebral artery and 102 (57 culprit and 45 nonculprit) in the basilar artery. Nearly 90% of culprit lesions had a degree of luminal stenosis of P =0.047), minimum luminal area (OR, 1.468 [95% CI, 1.032–2.087]; P =0.033), and coefficient of variation (OR, 13.425 [95% CI, 3.987–45.204]; P P =0.029), intraplaque hemorrhage (OR, 2.847 [95% CI, 0.971–10.203]; P =0.046), and coefficient of variation (OR, 10.068 [95% CI, 2.820–21.343]; P Conclusions: Features characterized by high-resolution magnetic resonance imaging provided complementary values over luminal stenosis in defined lesion type for intracranial atherosclerosis; the dispersion of signal intensity in histogram analysis was a particularly effective predictive parameter.

Objective: MARK4 (microtubule affinity-regulating kinase 4) regulates NLRP3 (nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing 3) inflammasome activation. The aim of the study is to examine the role of MARK4 in hematopoietic cells during atherosclerosis. Methods and Results: We show increased MARK4 expression in human atherosclerotic lesions compared with adjacent areas. MARK4 is coexpressed with NLRP3, and they colocalize in areas enriched in CD68-positive but α-SMA (α-smooth muscle actin)–negative cells. Expression of MARK4 and NLRP3 in the atherosclerotic lesions is associated with the production of active IL (interleukin)-1β and IL-18. To directly assess the role of hematopoietic MARK4 in NLRP3 inflammasome activation and atherosclerotic plaque formation, Ldlr (low-density lipoprotein receptor)-deficient mice were lethally irradiated and reconstituted with either wild-type or Mark4 -deficient bone marrow cells, and were subsequently fed a high-fat diet and cholesterol diet for 9 weeks. Mark4 deficiency in bone marrow cells led to a significant reduction of lesion size, together with decreased circulating levels of IL-18 and IFN-γ (interferon-γ). Furthermore, Mark4 deficiency in primary murine bone marrow–derived macrophages prevented cholesterol crystal–induced NLRP3 inflammasome activation, as revealed by reduced caspase-1 activity together with reduced production of IL-1β and IL-18. Conclusions: MARK4-dependent NLRP3 inflammasome activation in the hematopoietic cells regulates the development of atherosclerosis.

Background— Atherosclerotic plaques underlying most myocardial infarctions have thin fibrous caps and large necrotic cores; however, these features alone do not reliably identify plaques that rupture. Rupture occurs when plaque structural stress (PSS) exceeds mechanical strength. We examined whether PSS could be calculated in vivo based on virtual histology (VH) intravascular ultrasound and whether PSS varied according to plaque composition, subtype, or clinical presentation. Methods and Results— A total of 4429 VH intravascular ultrasound frames from 53 patients were analyzed, identifying 99 584 individual plaque components. PSS was calculated by finite element analysis in whole vessels, in individual plaques, and in higher-risk regions (plaque burden ≥70%, mean luminal area ≤4 mm 2 , noncalcified VH-defined thin-cap fibroatheroma). Plaque components including total area/arc of calcification ( R 2 =0.33; P R 2 =0.28; P R 2 =0.18; P R 2 =0.15; P P =0.002). PSS was also higher in patients with an acute coronary syndrome, where mean luminal area ≤4 mm 2 (8.24 [7.06–9.93] versus 7.72 [6.33–9.34]; P =0.03), plaque burden ≥70% (9.18 [7.44–10.88] versus 7.93 [6.16–9.46]; P =0.02), and in noncalcified VH-defined thin-cap fibroatheroma (9.23 [7.33–11.44] versus 7.65 [6.45–8.62]; P =0.02). Finally, PSS increased the positive predictive value for VH intravascular ultrasound to identify clinical presentation. Conclusions— Finite element analysis modeling demonstrates that structural stress is highly variable within plaques, with increased PSS associated with plaque composition, subtype, and higher-risk regions in patients with acute coronary syndrome. PSS may represent a novel tool to analyze the dynamic behavior of coronary plaques with the potential to improve prediction of plaque rupture.

Background Gadolinium enhancement on high‐resolution magnetic resonance imaging ( MRI ) has been proposed as a marker of inflammation and instability in intracranial atherosclerotic plaque. We performed a systematic review and meta‐analysis to summarize the association between intracranial atherosclerotic plaque enhancement and acute ischemic stroke. Methods and Results We searched the medical literature to identify studies of patients undergoing intracranial vessel wall MRI for evaluation of intracranial atherosclerotic plaque. We recorded study data and assessed study quality, with disagreements in data extraction resolved by a third reader. A random‐effects odds ratio was used to assess whether, in any given patient, cerebral infarction was more likely in the vascular territory supplied by an artery with MRI ‐detected plaque enhancement as compared to territory supplied by an artery without enhancement. We calculated between‐study heterogeneity using the Cochrane Q test and publication bias using the Begg‐Mazumdar test. Eight articles published between 2011 and 2015 met inclusion criteria. These studies provided information about plaque enhancement characteristics from 295 arteries in 330 patients. We found a significant positive relationship between MRI enhancement and cerebral infarction in the same vascular territory, with a random effects odds ratio of 10.8 (95% CI 4.1–28.1, P P =0.14) or publication bias ( P =0.80) was present. Conclusions Intracranial plaque enhancement on high‐resolution vessel wall MRI is strongly associated with ischemic stroke. Evaluation for plaque enhancement on MRI may be a useful test to improve diagnostic yield in patients with ischemic strokes of undetermined etiology.

Background— Although plaque rupture is responsible for most myocardial infarctions, few high-risk plaques identified by intracoronary imaging actually result in future major adverse cardiovascular events (MACE). Nonimaging markers of individual plaque behavior are therefore required. Rupture occurs when plaque structural stress (PSS) exceeds material strength. We therefore assessed whether PSS could predict future MACE in high-risk nonculprit lesions identified on virtual-histology intravascular ultrasound. Methods and Results— Baseline nonculprit lesion features associated with MACE during long-term follow-up (median: 1115 days) were determined in 170 patients undergoing 3-vessel virtual-histology intravascular ultrasound. MACE was associated with plaque burden ≥70% (hazard ratio: 8.6; 95% confidence interval, 2.5–30.6; P 2 (hazard ratio: 6.6; 95% confidence interval, 2.1–20.1; P =0.036), although absolute event rates for high-risk lesions remained P P =0.02). Furthermore, PSS improved the ability of virtual-histology intravascular ultrasound to predict MACE in plaques with plaque burden ≥70% (adjusted log-rank, P =0.003) and minimal luminal area ≤4 mm 2 ( P =0.002). Plaques responsible for MACE had larger superficial calcium inclusions, which acted to increase PSS ( P Conclusions— Baseline PSS is increased in plaques responsible for MACE and improves the ability of intracoronary imaging to predict events. Biomechanical modeling may complement plaque imaging for risk stratification of coronary nonculprit lesions.

Background and Purpose— It has been hypothesized that high structural stress in atherosclerotic plaques at critical sites may contribute to plaque disruption. To test that hypothesis, 3D fluid-structure interaction models were constructed based on in vivo MRI data of human atherosclerotic carotid plaques to assess structural stress behaviors of plaques with and without rupture. Methods— In vivo MRI data of carotid plaques from 12 patients scheduled for endarterectomy were acquired for model reconstruction. Histology confirmed that 5 of the 12 plaques had rupture. Plaque wall stress (PWS) and flow maximum shear stress were extracted from all nodal points on the lumen surface of each plaque for analysis. A critical PWS (maximum of PWS values from all possible vulnerable sites) was determined for each plaque. Results— Mean PWS from all ulcer nodes in ruptured plaques was 86% higher than that from all nonulcer nodes (123.0 versus 66.3 kPa, P P P =0.0016 using log transformation). Conclusion— The results of this study show that plaques with prior ruptures are associated with higher critical stress conditions, both at ulcer sites and when compared with nonruptured plaques. With further validations, plaque stress analysis may provide additional stress indicators helpful for image-based plaque vulnerability assessment.

Supplemental Digital Content is available in the text, This study sought to report the mid-term outcome of a modified flow-diverting strategy in the treatment of complicated aortic aneurysms of different morphology. Historical data suggested aortic aneurysm expansion and rupture after endovascular treatment with current commercial flow-diverters, indicating the essentiality of further investigation of this technique prior to its large-scale clinical application. An alternative flow-diverting strategy using layer-by-layer assembled multiple overlapping uncovered stents was employed in this study. The treatment outcome in aneurysms of different morphology (saccular, fusiform, and dissecting) was assessed during a mid-term follow-up period. Of 42 patients enrolled in this study (30 male, mean age: 63.3 years), technical success was achieved in 40 cases. During an average follow-up period of 20.9 months, mean aneurysm diameter shrunk from 53.4 ± 13.6 mm to 48.8 ± 13.9 mm (P