BackgroundAtherosclerosis is a systemic disease that usually affects multi-vascular beds, and high-risk atherosclerotic plaques (HRPs) are associated with ischemic events.PurposeTo investigate the prevalence and risk factors of co-existing extracranial carotid and intracranial artery HRPs using magnetic resonance vessel wall imaging (MR-VWI).Material and MethodsParticipants (n = 190; 120 men, mean age = 63.4 ± 9.4 years) with co-existing extracranial carotid and intracranial plaques were recruited from a multicenter observational study of CARE-II. All patients underwent carotid MR-VWI and intracranial MRA at 3.0 T. The prevalence of risk factors between the non-HRP, single HRP, and co-existing HRPs groups was compared. Multivariate logistic regression analysis was used to determine the associations between risk factors and the three groups.ResultsAmong 190 patients, 77 (40.5%) were in the non-HRP group, 78 (41.1%) were in the single HRP group, and 35 (18.4%) were in the co-existing HRPs groups. Multivariate regression analysis showed that patients in the co-existing HRPs group were more likely to have a higher prevalence of diabetes (OR = 3.92, 95% CI = 1.53-10.04; P = 0.004) and family history of cardiovascular disease (CVD) (OR = 3.37, 95% CI = 1.26-8.98; P = 0.015) compared to the non-HRP group after adjusting for age, sex, high-density lipoprotein (HDL), and smoking. Similarly, patients with co-existing HRPs were more likely to have higher prevalence of diabetes (OR = 2.49, 95% CI = 1.04-5.95; P = 0.040) compared to the single HRP group after adjusting for age, sex, and HDL.ConclusionCo-existing extracranial carotid and intracranial artery HRPs are observed in middle-aged and elderly symptomatic atherosclerotic patients. Diabetes and family history of CVD are independent risk factors for co-existing HRPs.

Rationale and Objectives Increasing evidence links large artery atherosclerosis to cerebral small vessel disease(CSVD), but the relationship between carotid vulnerable plaque features and lacunar infarction (LAC) remains unclear. This study investigates this association in patients with moderate-to-severe carotid stenosis. Materials and Methods Patients with symptomatic 50–99% or asymptomatic 70–99% carotid stenosis referred for carotid endarterectomy were recruited. All underwent carotid vessel wall and brain MRI. Plaque burden and compositional characteristics were assessed. LAC presence was determined and severity categorized as mild (1−5), moderate (6−10), or severe (>10 infarcts). Logistic regression analyzed associations of plaque features with LAC presence and severity. Results Among 194 patients (84% male, mean age 65.3±8.0 years), 110 (56.7%) had LAC. LAC patients had larger calcification volume (OR 1.004, 95%CI 1.000–1.007) and calcified area percentage (OR 1.052, 95%CI 1.017–1.089). Mild and moderate LAC also showed larger calcified area percentages (OR 1.060, 95%CI 1.019–1.102 and OR 1.061, 95%CI 1.012–1.113, respectively). Severe LAC patients had higher LRNC (OR 1.002, 95%CI 1.000–1.003) and IPH volumes (OR 1.003, 95%CI 1.001–1.006). Conclusion Our study demonstrates that LAC patients exhibit significantly greater carotid plaque calcification burden, particularly in mild-to-moderate cases, with these associations remaining statistically significant after multivariable adjustment. Severe LAC shows stronger correlations with IPH and LRNC volumes, suggesting that vulnerable plaque characteristics may mediate distinct pathophysiological mechanisms in patients with severe LAC.

BACKGROUND:It has been shown that rupture of vulnerable plaques of atherosclerosis (AS) is one of the main causes of ischemic stroke. Increasing evidence suggests that the inflammatory changes of perivascular adipose tissue (PVAT) were independently associated with both vulnerable plaque characteristics and cerebrovascular symptoms. Therefore, it is essential to conduct non-invasive joint assessment of carotid AS plaques and PVAT characteristics for better stratifying the risk of ischemic cerebrovascular events. PURPOSE:To develop a simultaneous magnetic resonance (MR) imaging technique for carotid artery PVAT and vessel wall, and determine its feasibility and repeatability. METHODS:This study developed an MR sequence for simultaneous imaging carotid vessel wall and PVAT. Seventeen healthy subjects and nine patients with carotid AS were recruited for MR imaging experiments, of whom five healthy subjects were selected for the repeatability test. All participants underwent bilateral carotid three-dimensional MR imaging by acquiring the proposed iMSDE-mDIXON, MERGE, and mDIXON sequences. To evaluate the reliability of the proposed iMSDE-mDIXON sequence, we analyzed its agreement in measuring morphology (lumen area, wall area, mean wall thickness, and normalized wall index) of carotid wall with the reference sequence of MERGE, as well as its agreement in quantifying carotid PVAT (PVAT area, proton density fat fraction [PDFF], area index, and volume index) with the reference sequence of mDIXON. The interclass correlation coefficient (ICC) and Bland-Altman plots were conducted in statistical analysis. RESULTS:The proposed iMSDE-mDIXON technique demonstrated high reliability in quantifying carotid vessel wall morphology (healthy subjects: ICC = 0.903-0.997; patients: ICC = 0.928-0.999) and PVAT morphology (healthy subjects: ICC = 0.906-0.988; patients: ICC = 0.957-0.996). Although iMSDE-mDIXON sequence showed potential in assessing carotid AS, there was a substantial bias (>20%) in PDFF quantification. Nevertheless, moderate to excellent agreement was maintained between iMSDE-mDIXON and mDIXON in measuring PVAT PDFF both in healthy subjects (ICC: left, 0.782; right, 0.740) and AS patients (ICC: left, 0.790; right, 0.628). In addition, the proposed sequence showed excellent agreement in quantifying carotid vessel wall (ICC = 0.845-0.999) and PVAT morphology (ICC = 0.841-0.989) between the repeated scans. CONCLUSIONS:This study proposed an iMSDE-mDIXON sequence that enables simultaneous imaging of the carotid vessel wall and PVAT in a single scan with high efficiency, reliability, and repeatability. This technique has considerable potential for jointly characterizing the changes of PVAT and pathology of the vessel wall in carotid artery.

OBJECTIVE:Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease leading to astrocytic and neurovascular unit injury. Although BBB structural disruption during acute attacks is well established, BBB water exchange during clinical remission remains unclear. This study aimed to quantify BBB water exchange in remission phase NMOSD using water-extraction-with-phase-contrast arterial spin labeling (WEPCAST) MRI and compare these findings with those in relapsing remitting multiple sclerosis (RRMS) and healthy controls (HCs). METHODS:Twenty-seven patients with NMOSD (42.5 ± 11.2 years, 27 females), 18 patients with RRMS (36.9 ± 11.9 years, 16 females), and 22 age- and sex-matched HCs (43.1 ± 9.5 years, 22 females) were prospectively enrolled. Remission was defined as no clinical relapse or new MRI lesion within 3 months before imaging. Brain MRI included FLAIR, phase contrast, T1 weighted, and WEPCAST sequences. BBB water exchange was quantified using the WEPCAST derived permeability-surface area product (PS), and quantitative white matter hyperintensity (WMH) volume was assessed on FLAIR images. Pairwise linear regression analyses were used for group comparison with covariate adjustment. RESULTS:NMOSD patients in remission demonstrated significantly higher PS values (141.5 ± 33.7 ml/100 g/min) than RRMS patients (117.8 ± 20.8 mL/100 g/min; p < 0.05) and HCs (120.3 ± 16.8 mL/100 g/min; p < 0.05), whereas RRMS did not differ from HCs. In pairwise regression analyses, PS remained significantly higher in NMOSD than in RRMS and HCs after covariate adjustment and after additional adjustment for WMH volume. CONCLUSION:WEPCAST derived PS is higher in remission phase NMOSD than in RRMS and HCs, suggesting altered BBB water exchange during clinical remission. These exploratory group level findings warrant validation in larger longitudinal cohorts.

BACKGROUND:Plaque rupture is influenced by both plaque components and the dynamic behavior of the arterial wall. This study aimed to characterize dynamic changes in carotid lumen and wall using magnetic resonance black blood cine imaging and to determine their value in discriminating plaque vulnerability. METHODS:Patients with symptomatic carotid atherosclerotic stenosis scheduled for carotid endarterectomy were recruited and underwent black blood cine imaging. Histological slices were used to identify intraplaque hemorrhage, lipid-rich necrotic core, calcification, loose matrix, and fibrous cap rupture, and were matched with magnetic resonance images. Dynamic changes in lumen area, wall area, normalized wall index (NWI), and maximum wall thickness were calculated, while static measurements were derived by averaging these parameters over cardiac phases. These measurements were compared using independent t test or Mann-Whitney U test, depending on data normality. Logistic regression and receiver operating characteristic analyses were conducted to discriminate fibrous cap rupture and to distinguish symptomatic status. RESULTS:Eighty magnetic resonance cine slices from 29 patients (mean age, 64.9±7.6 years; 22 males) were matched with histology. Slices with intraplaque hemorrhage (P=0.019) or lipid-rich necrotic core (P=0.016) exhibited lower NWI changes. Maximum wall thickness changes were higher in slices with loose matric (P=0.032) but reduced in slices with calcification (P=0.036). Maximum wall thickness changes were protective against fibrous cap rupture (odds ratio, 0.871; P=0.008; area under the receiver operating characteristic curve, 0.765). Symptomatic arteries showed lower maximum wall thickness, wall area, and NWI changes, but higher lumen area changes (P<0.05). Static lumen area and NWI were significantly altered in slices with intraplaque hemorrhage, lipid-rich necrotic core, or loose matrix (P<0.05), but static measurements showed no significant association with fibrous cap rupture. In discriminating symptomatic from asymptomatic arteries, combining NWI and lumen area changes achieved an area under the receiver operating characteristic curve of 0.946, whereas static NWI reached an area under the receiver operating characteristic curve of 0.971. CONCLUSIONS:Dynamic changes assessed by magnetic resonance black blood cine imaging are associated with plaque components, fibrous cap rupture, and symptomatic status, suggesting their potential as quantitative markers of plaque vulnerability.

Background: Cerebrovascular hemodynamics are believed to play an important role in the development of ischemic stroke (IS). However, the relationships between hemodynamics and prognosis are not fully understood. Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) enables comprehensive characteristics of cerebrovascular hemodynamics. This study aims to investigate the associations of the different hemodynamics derived from 4D flow CMR with IS functional outcomes. Methods: Ninety-one patients (median age 64 years, 62 males) with unilateral IS in middle cerebral artery (MCA) territory were included. All subjects underwent a CMR scan, including 4D flow, three-dimensional (3D) time-of-flight magnetic resonance angiography, and 3D whole brain black-blood high-resolution vessel wall imaging of the MCA. Six hemodynamic parameters, including flow rate, velocity, pulsatility index, time-averaged wall shear stress (TAWSS), oscillatory shear index, and relative residence time (RRT), were calculated for the lesion site, pre-bifurcation M1 (pM1) segment, and the distal M1 and/or first branches of M2 (dM1/M2) segments. Vessel characteristics, such as lumen area, vessel area, wall area, maximum wall thickness, and the degree of stenosis, were calculated at the most stenotic lesion site. The modified Rankin Scale (mRS) scores were assessed at 90 days and 1 year, and an mRS > 2 was considered as a poor functional outcome. Results: Lower segment-level TAWSS (odds ratio [OR]: 0.24, P = 0.006 and OR: 0.29, P = 0.014), higher RRT (OR: 2.74, P = 0.007 and OR: 2.40, P = 0.011) of dM1/M2 segments, and lower segment-and lesion-level velocity (OR: 0.40, P = 0.019 and OR: 0.41, P = 0.025; OR: 0.41, P = 0.030 and OR: 0.42, P = 0.040) of pM1 segment were observed to be associated with poor functional outcome at both 90 days and 1 year. Using the cutoff value of 3.58 Pa and 0.29, respectively, TAWSS and RRT of dM1/M2 segments showed moderate performance in distinguishing poor functional outcome from favorable outcome (area under the curve ranging from 0.642-0.687) both at 90 days and 1 year. Conclusion: Distal segmental TAWSS and RRT of dM1/M2 segments were associated with poor functional outcomes. Such alterations in hemodynamics might help in the identification of patients with potentially unfavorable prognosis.

Background:Hemodynamics is crucial for the assessment of atherosclerotic development. However, flow alterations due to plaque existence and increased plaque number in different intracranial arterial segments have not been fully understood. This study aimed to investigate the relationship of wall shear stress (WSS) parameters between middle cerebral arteries (MCAs) with and without plaque and explore the potential discrepancy between multiple- and single-plaque existence. Methods:Consecutive patients with MCA atherosclerosis were recruited and underwent four-dimensional (4D) flow magnetic resonance imaging (MRI) and three-dimensional (3D) vessel wall imaging (VWI). Time-averaged WSS (TAWSS), time-averaged WSS coefficient variation (TAWSSCV), and oscillatory shear index (OSI) were measured at five cross-sectional slices [initial, upstream, the most narrowed lumen (MNL), downstream, and terminal] of plaque and reference (REF) sites to describe lesion-level hemodynamics. Segment-level hemodynamics of M1 and M2 segments were also analyzed. MCA geometry and plaque characteristics were calculated. The MCAs were then classified into four groups according to plaque presence in different segments: Group I, without plaque; Group II, with plaque only in M1; Group III, with plaque in both M1 and M2; Group IV, with plaque only in M2. The above parameters were compared in MCA with and without plaque as well as single- and multiple-plaque (≥2) MCAs. Results:A total of 150 MCAs with 231 plaques from 79 patients were investigated. TAWSSmin showed a relatively larger value at the proximal portion compared to the distal portion across plaque in both M1 and M2 segments. Lower lesion-level TAWSSmin was found in the M1 plaque presence of Group III compared to Group I and Group II (P=0.026 and P=0.014). Similar association was also observed in the M2 plaque presence of Groups III and IV compared to Group I (P=0.010 and P=0.008), whereas lower segment-level TAWSSmin was only seen in the M2 segment of Group III compared to Group I (P=0.039). Lower OSImean was found both in the M1 presence of Group II and III compared to Group I (P=0.013 and P=0.048) and OSImax was found in the M1 plaque presence of Group II compared to Group I (P=0.036). Lower stenosis was found in single-plaque compared to multiple-plaque groups (P=0.045 and P=0.049). Lower lesion-level highest/initial TAWSSmean ratio (P=0.037) and highest/initial TAWSSmax ratio (P=0.013) were found in the single-plaque M1 group compared to the multiple-plaque M1 group. The M1 geometry and positive remodeling (PR) were different between single- and multiple-plaque M1 groups whereas maximum wall thickness (maxWT) and normalized wall index (NWI) showed differences between the single- and multiple-plaque M2 groups (all P<0.05). Conclusions:Hemodynamic alterations are observed under the impacts of atherosclerosis and are different between M1 plaque and M2 plaque. Single- and multiple-plaque MCAs exhibit different geometry, plaque characteristics, and hemodynamics, and these vary according to segments. The interplay of arterial segment, plaque number, and characteristics as well as hemodynamics could provide insight for the mechanisms of atherosclerotic existence.

BACKGROUND: This study aimed to explore the association between the amount of carotid artery perivascular adipose tissue (PVAT) quantified by magnetic resonance imaging and prior cerebral infarction. METHODS: A total of 139 patients (mean age, 64.4±8.2 years; 112 men) with moderate-to-severe atherosclerotic stenosis referred to carotid endarterectomy were included and underwent multicontrast magnetic resonance vessel wall and brain imaging. The amount of carotid artery PVAT with vulnerable plaque components on magnetic resonance images of each patient was quantitatively analyzed, and the measurements included the average PVAT area, PVAT area index, and PVAT volume index. The amount measurements of PVAT at slices with vulnerable plaque between patients with and without prior cerebral infarction were compared. Logistic regression analyses were conducted to determine the association between the amount measurements of PVAT and prior cerebral infarction. RESULTS: Patients with prior cerebral infarction showed significantly higher PVAT area, PVAT area index, and PVAT volume index compared with those without (all P <0.01). The carotid PVAT area (odds ratio [OR], 1.015 [95% CI, 1.003–1.028]; P =0.018), PVAT area index (OR, 2.051 [95% CI, 1.084–3.880]; P =0.027), and PVAT volume index (OR, 2.864 [95% CI, 1.343–6.108]; P =0.006) on the index side were significantly associated with prior cerebral infarction in univariate logistic regression. After adjusting for clinical confounding factors and plaque features, the associations between the carotid PVAT area (OR, 1.028 [95% CI, 1.008–1.048]; P =0.006), PVAT area index (OR, 3.587 [95% CI, 1.451–8.870]; P =0.006), and PVAT volume index (OR, 6.053 [95% CI, 2.048–17.889]; P =0.001) and prior cerebral infarction remained statistically significant. CONCLUSIONS: The amount of PVAT in carotid artery with vulnerable plaques is independently associated with prior cerebral infarction and may, therefore, be related to the occurrence of ischemic stroke.

BACKGROUND:This study aimed to explore the association between the amount of carotid artery perivascular adipose tissue (PVAT) quantified by magnetic resonance imaging and prior cerebral infarction. METHODS:A total of 139 patients (mean age, 64.4±8.2 years; 112 men) with moderate-to-severe atherosclerotic stenosis referred to carotid endarterectomy were included and underwent multicontrast magnetic resonance vessel wall and brain imaging. The amount of carotid artery PVAT with vulnerable plaque components on magnetic resonance images of each patient was quantitatively analyzed, and the measurements included the average PVAT area, PVAT area index, and PVAT volume index. The amount measurements of PVAT at slices with vulnerable plaque between patients with and without prior cerebral infarction were compared. Logistic regression analyses were conducted to determine the association between the amount measurements of PVAT and prior cerebral infarction. RESULTS:Patients with prior cerebral infarction showed significantly higher PVAT area, PVAT area index, and PVAT volume index compared with those without (all P<0.01). The carotid PVAT area (odds ratio [OR], 1.015 [95% CI, 1.003-1.028]; P=0.018), PVAT area index (OR, 2.051 [95% CI, 1.084-3.880]; P=0.027), and PVAT volume index (OR, 2.864 [95% CI, 1.343-6.108]; P=0.006) on the index side were significantly associated with prior cerebral infarction in univariate logistic regression. After adjusting for clinical confounding factors and plaque features, the associations between carotid PVAT area (OR, 1.028 [95% CI, 1.008-1.048]; P=0.006), PVAT area index (OR, 3.587 [95% CI, 1.451-8.870]; P=0.006), and PVAT volume index (OR, 6.053 [95% CI, 2.048-17.889]; P=0.001) and prior cerebral infarction remained statistically significant. CONCLUSIONS:The amount of PVAT in carotid artery with vulnerable plaques is independently associated with prior cerebral infarction and may, therefore, be related to the occurrence of ischemic stroke.

This study sought to evaluate the relationship between morphological and compositional characteristics of carotid atherosclerotic plaques and white matter lesions (WMLs) in asymptomatic elderly adults using three-dimensional (3D) multicontrast magnetic resonance (MR) vessel wall imaging. Asymptomatic elderly subjects (≥ 60 years) were recruited from a community-based study. Carotid arteries and the brain were imaged on a 3.0-T MR scanner. The morphological and compositional features of carotid atherosclerotic plaques were evaluated. The WMLs were scored using the Fazekas criteria. The characteristics of carotid plaque were compared among different WML severities and the associations between carotid plaque characteristics and WMLs were analyzed. In total, 123 elderly subjects (mean age: 71.9 ± 6.0 years, 55 males) were included. A significant difference was found in carotid MWT, presence of calcification, and high-risk plaque among subjects with different severity of WMLs (all p < 0.05). Univariate logistic regression analysis showed that carotid plaque calcification (OR, 5.357; 95

BACKGROUND:Multi-parametric imaging of the carotid artery enables quantitative characterization of vulnerable atherosclerotic plaques, which is crucial for preventing ischemic stroke. However, the existing sequential acquisition-based multi-parametric imaging techniques of carotid artery lack bright blood imaging, which is essential for plaque components identification and boundary delineation. This study aims to develop a joint bright, gray, and black blood imaging technique for carotid artery multi-parametric imaging and validate its accuracy and feasibility. METHODS:The proposed technique incorporated variable flip angles, variable duration of improved motion-sensitized driven equilibrium prepulse, and variable time of echo mapping strategies with three-dimensional multi-shot spoiled gradient-recalled echo acquisition, generating T1, T2, and T2* maps. Bright, gray, and black blood images were sequentially acquired in six scans covering the entire extracranial artery with isotropic resolution (0.7 mm) when natural inflow blood enhancement and imposed blood suppression module were alternatively performed. A B1-specific dictionary was simulated and matched to the measured signal for T1 and T2 estimation while least square fitting was applied for T2* estimation. The proposed technique was compared against reference sequences and validated in healthy volunteers (n = 8) and patients (n = 4) with carotid atherosclerotic plaques. RESULTS:The proposed technique achieved an agreement of R2 = 0.99 in T1, T2, and T2* measurements with standard sequences in phantom study. In healthy volunteer study, the proposed technique reached high intraclass correlation coefficients (ICC: 0.906-0.956) with reference sequences in measuring T1, T2, and T2* of cervical muscle, but overestimation and underestimation were observed in T1 (against modified Look-Locker inversion-recovery, bias = 4.8%) and T2 (against gradient and spin echo sequence, bias = -3.3%), respectively. No significant difference was found in the measurement of morphology and quantitative parameters between scan and rescan, while excellent intra- (ICC: 0.804-0.999) and inter-observer (ICC: 0.816-0.982) repeatability was reached. In patient study, the proposed technique demonstrated reliable performance in analyzing vascular morphology and characterizing plaque components with distinctive signal characteristics and quantitative values. CONCLUSION:The proposed technique enables joint bright, gray, and black blood imaging technique for carotid artery multi-parametric imaging with large coverage and isotropic resolution, indicating clinical potential for comprehensive characterization of carotid vulnerable plaque.

BACKGROUND:While diabetes mellitus (DM) is an established risk factor for intracranial atherosclerotic disease (ICAD), its impact on plaque characteristics across different intracranial vascular territories remains unclear. METHODS:Patients with symptomatic intracranial artery stenosis were recruited from a multi-center study of ICASMAP. Plaque characteristics, including the location, plaque burden measured by normalized wall index (NWI), luminal stenosis, length, T1 hyperintense, enhancement grade, and the enhancement ratio of atherosclerotic plaques were evaluated. Plaque characteristics were compared between patients with and without DM and the association between DM and plaque characteristics was analyzed. RESULTS:Of 171 recruited patients (mean age: 59.1 ± 8.9 years; 91 males), 76 (44.4 %) had DM. Diabetic patients had significantly greater luminal stenosis (49.6 %±25.6 % vs. 29.3 %±18.0 %, P < 0.001), length of plaque (9.3 ± 2.9 mm vs. 7.9 ± 3.9 mm, P = 0.001), NWI (82.9 %±13.0 % vs. 75.9 %±15.4 %, P = 0.012), plaque enhancement Grade 0 (22.4 % vs. 48.0 %, P = 0.005), and plaque enhancement Grade 1 (72.4 % vs. 48.0 %, P = 0.009) in the ophthalmic and communion segment of the internal carotid artery compared with non-diabetic patients. In the basilar artery, there were significant differences in luminal stenosis (57.5 %±28.3 % vs. 42.5 %±25.8 %, P = 0.026), length of plaque (16.6 ± 8.2 mm vs. 10.2 ± 5.3 mm, P < 0.001), and plaque enhancement Grade 1 (77.1 % vs. 51.4 %, P = 0.025) between diabetic and non-diabetic patients. No significant differences were observed in the M1-2 segment of the middle cerebral artery or the V4 segment of the vertebral artery. Adjusting for confounding factors, the differences remained statistically significant in luminal stenosis (P = 0.001), NWI (P = 0.011), plaque enhancement Grade 1 (P = 0.033), and plaque enhancement Grade 2 (P = 0.048) in the ophthalmic and communion segments of internal carotid artery and luminal stenosis (P = 0.001), length of plaque (P = 0.006) in basilar artery between diabetic and non-diabetic patients. CONCLUSION:DM differentially affects atherosclerotic plaque characteristics across intracranial artery segments, predominantly the ophthalmic and communion segments of the internal carotid artery and basilar artery.

Background Accurate assessment of the vulnerability of carotid atherosclerotic plaques is crucial for stroke prevention. The three-dimensional (3D) magnetic resonance (MR) vessel wall imaging (VWI) has been increasingly employed to evaluate carotid plaques due to its extensive coverage and isotropic high spatial resolution. However, the accuracy of such technique lacks validation by histology. Objective This study aims to validate the accuracy of 3D multi-contrast MR VWI used variable-flip-angle (VFA) and turbo spin echo (TSE) readout in identifying vulnerable carotid plaques, using histological analysis as a reference. Methods Twenty-one male patients (mean age: 64.4 ± 7.2 years) scheduled for carotid endarterectomy (CEA) were recruited for this study. All patients underwent carotid multi-contrast MR VWI, including 3D T1- and T2-weighted variable flip angle-based turbo spin echo (VFA-TSE) sequences, as well as 3D time of flight (TOF) MR angiography (MRA), using a 3.0T MR system. Histological processing was performed for carotid plaque specimens. The presence or absence, along with the area measurements, of lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), and calcifications (CA) were independently evaluated on both MR images and histological sections. Cohen’s kappa (κ) analysis was utilized to determine the agreement between 3D multi-contrast MR VWI and histology in identifying carotid plaque compositions before and after excluding compositions bellow certain size threshold. Spearman’s correlation analysis was also conducted to assess the agreement in quantifying plaque compositions. Results A total of 81 slices of MR images were successfully matched with histological sections. Moderate to almost perfect agreements were observed between 3D MR VWI and histology in the identification of LRNC (κ: 0.85 and 0.89), IPH (κ: 0.65 and 0.69), and CA (κ: 0.46 and 0.62) before and after excluding compositions smaller than 0.79 mm2. Strong to very strong correlations were found in the quantification of plaque compositions including LRNC (r=0.88), IPH (r=0.80), and CA (r=0.74) between MR imaging and histology. Conclusion The 3D VFA-TSE multi-contrast MR VWI is capable of accurately characterizing vulnerable carotid atherosclerotic plaques.

Purpose: Intracranial artery atherosclerosis (ICAS) progression is associated with stroke. However, the association of carotid plaque with ICAS progression among stroke-free participants is still unclear. This study aimed to evaluate the association between carotid plaque and ICAS progression in stroke-free participants. Method: Stroke-free participants were recruited from a community-based cohort study. All participants underwent questionnaire interviews, blood tests, and high-resolution vessel wall magnetic resonance (MR) imaging at baseline and follow-up for around three years. The atherosclerotic plaque was defined as eccentric wall thickening on MR imaging. The presence, location, total number, and burden (maximum wall thickness, length, and stenosis) of carotid and intracranial plaque were evaluated. ICAS progression was defined as the number increased or plaque burden (maximum wall thickness, length, or stenosis increase) increased by >= 20 %. The association between carotid plaque and ICAS progression was evaluated using multivariable logistic regression. Results: Of the 312 participants (mean age at baseline: 59.85 +/- 13.04 years; 136 males) who completed baseline and follow-up studies with a mean time interval of 3.15 +/- 0.59 years, 85 (27.24 %) had progression of ICAS during follow-up. At least one carotid plaque was detected at baseline in 167 (53.53 %) participants. In the multivariable logistic analysis, carotid plaque was a significant predictor for the progression of ICAS (odds ratio, 2.04; 95 % confidence interval, 1.06-3.92; P = 0.032). Conclusions: Carotid plaque is associated with intracranial artery atherosclerosis progression in stroke-free population. Our findings suggest that carotid plaque may be an effective predictor for intracranial artery atherosclerosis progression.

Background: Accurate assessment of the vulnerability of carotid atherosclerotic plaques is crucial for stroke prevention. The three-dimensional (3D) magnetic resonance (MR) vessel wall imaging (VWI) has been increasingly employed to evaluate carotid plaques due to its extensive coverage and isotropic high spatial resolution. However, the accuracy of such techniques lacks validation by histology. Therefore, this study aims to validate the accuracy of 3D multi-contrast MR VWI with variable-flip-angle (VFA) and turbo spin echo (TSE) readout in identifying vulnerable carotid plaques, using histological analysis as a reference. Methods: Twenty-one male patients (mean age: 64.4 +/- 7.2 years old) scheduled for carotid endarterectomy (CEA) were recruited in this study. All patients underwent carotid multi-contrast MR VWI, including 3D T1- and T2-weighted VFA-TSE sequences, as well as 3D time of flight (TOF) MR angiography (MRA), using a 3.0T MR system before surgery. Histological processing was performed for carotid plaque specimens. The presence or absence, along with the area measurements, of lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), and calcifications (CA) were independently evaluated on both MR images and histological sections. Cohen's kappa (kappa) analysis was utilized to determine the agreement between 3D multi-contrast MR VWI and histology in identifying carotid plaque compositions before and after excluding compositions bellow certain size threshold. Spearman's correlation analysis was also conducted to assess the agreement in quantifying plaque compositions. Results: A total of 81 slices of MR images were successfully matched with histological sections. Moderate to almost perfect agreements were observed between 3D MR VWI and histology in the identification of LRNC (kappa: 0.85 and 0.89), IPH (kappa: 0.65 and 0.69), and CA (kappa: 0.46 and 0.62) before and after excluding compositions smaller than 0.79 mm2. Strong to very strong correlations were found in the quantification of plaque compositions including LRNC (r=0.88), IPH (r=0.80), and CA (r=0.74) between MR imaging and histology. Conclusion: The 3D VFA-TSE multi-contrast MR VWI is capable of accurately characterizing vulnerable carotid atherosclerotic plaques.

Background Quantitative T1, T2, and T2* measurements of carotid atherosclerotic plaque are important in evaluating plaque vulnerability and monitoring its progression. Purpose To develop a sequence to simultaneously quantify T1, T2, and T2* of carotid plaque. Materials and Methods The simultaneous T1, T2, and T2* mapping of carotid plaque (SIMPLE*) sequence is composed of three modules with different T2 preparation pulses, inversion-recovery pulses, and acquisition schemas. Single-echo data were used for T1 and T2 quantification, while the multiecho (ME) data were used for T2* quantification. The quantitative accuracy of SIMPLE* was tested in a phantom study by comparing its measurements with those of reference standard sequences. In vivo feasibility of the technique was prospectively evaluated between November 2020 and February 2022 in healthy volunteers and participants with carotid atherosclerotic plaque. The Pearson or Spearman correlation test, Student t test, and Wilcoxon rank-sum test were used. Results T1, T2, and T2* estimated with SIMPLE* strongly correlated with inversion-recovery spin-echo (SE) (correlation coefficient [r] = 0.99), ME-SE (r = 0.99), and ME gradient-echo (r = 0.99) sequences in the phantom study. In five healthy volunteers (mean age, 25 years ± 3 [SD]; three women), measurements were similar between SIMPLE* and modified Look-Locker inversion recovery, or MOLLI (1151 msec ± 71 vs 1098 msec ± 64; P = .14), ME turbo SE (31 msec ± 1 vs 31 msec ± 1; P = .32), and ME turbo field echo (24 msec ± 2 vs 25 msec ± 2; P = .19). In 18 participants with carotid plaque (mean age, 65 years ± 9; 16 men), quantitative T1, T2, and T2* of plaque components were consistent with their signal characteristics on multicontrast images. Conclusion A quantitative technique for simultaneous T1, T2, and T2* mapping of carotid plaque with 100-mm3 coverage and 0.8-mm3 resolution was developed using the proposed SIMPLE* sequence and demonstrated high accuracy and in vivo feasibility. © RSNA, 2023 Supplemental material is available for this article.

Background: Magnetic resonance imaging (MRI) has the potential in assessing the inflammation of perivascular adipose tissue (PVAT) due to its excellent soft tissue contrast. However, evidence is lacking for the association between carotid PVAT measured by MRI and carotid vulnerable atherosclerotic plaques. This study aimed to investigate the association between signal intensity of PVAT and vulnerable plaques in carotid arteries using multi-contrast magnetic resonance (MR) vessel wall imaging. Methods: In this cross-sectional study, a total of 104 patients (mean age, 64.9±7.0 years; 86 men) with unilateral moderate-to-severe atherosclerotic stenosis referred to carotid endarterectomy (CEA) were recruited from April 2018 to December 2020 at Department of Neurosurgery of Peking University Third Hospital. All patients underwent multi-contrast MR vessel wall imaging including time-of-flight (ToF) MR angiography, black-blood T1-weighted (T1w) and T2-weighted (T2w) and simultaneous non-contrast angiography and intraplaque hemorrhage (IPH) imaging sequences. Patients with contraindications to endarterectomy or MRI examinations were excluded. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of PVAT were measured on ToF images and vulnerable plaque characteristics including IPH, large lipid-rich necrotic core (LRNC), and fibrous cap rupture (FCR) were identified. The SNR and CNR of PVAT were compared between slices with and without vulnerable plaque features using Mann-Whitney U test and their associations were analyzed using the generalized linear mixed model (GLMM). Results: Carotid artery slices with IPH (30.93±14.56 vs. 27.34±10.02; P<0.001), FCR (30.35±13.82 vs. 27.53±10.37; P=0.006), and vulnerable plaque (29.15±12.52 vs. 27.32±10.05; P=0.016) had significantly higher value of SNR of PVAT compared to those without. After adjusting for clinical confounders, the SNR of PVAT was significantly associated with presence of IPH [odds ratio (OR) =0.627, 95% confidence interval (CI): 0.465–0.847, Puncorr=0.002, PFDR=0.016] and vulnerable plaque (OR =0.762, 95% CI: 0.629–0.924, Puncorr=0.006, PFDR=0.020). However, no significant association was found between the CNR of PVAT and presence of vulnerable plaque features (all P>0.05). Conclusions: The SNR of carotid artery PVAT measured by ToF MR angiography is independently associated with vulnerable atherosclerotic plaque features, suggesting that the signal intensity of PVAT might be an effective indicator for vulnerable plaque.

PURPOSE:This study aimed to investigate the associations of atherosclerotic plaque characteristics in intracranial and extracranial carotid arteries with severity of white matter hyperintensities (WMHs) in symptomatic patients using magnetic resonance (MR) imaging. METHOD:Patients with cerebrovascular symptoms and carotid plaque were recruited from the cross-sectional, multicenter study of CARE-II. Luminal stenosis of intracranial and extracranial carotid arteries, carotid plaque compositional features, and WMHs were evaluated by brain structural and vascular MR imaging. The atherosclerotic plaque characteristics in intracranial and extracranial carotid arteries were compared between patients with and without moderate-to-severe WMHs (Fazekas score > 2), and their associations with severity of WMHs were analyzed using logistic regression. RESULTS:Of the recruited 622 patients (mean age, 58.7 ± 10.9 years; 422 males), 221 (35.5 %) had moderate-to-severe WMHs with higher prevalence of moderate-to-severe luminal stenosis (17.0 % vs. 10.4 %), intraplaque hemorrhage (15.7 % vs. 9.0 %), thin/ruptured fibrous cap (30.2 % vs. 20.4 %), calcification (44.4 % vs. 22.2 %) and lipid-rich necrotic core (63.8 % vs. 51.1 %) in carotid artery compared to those without (all P < 0.05). Multivariate logistic regression showed that carotid calcification (OR, 1.854; 95 % CI, 1.187-2.898; P = 0.007) was independently associated with moderate-to-severe WMHs after adjusting for confounding factors. No significant association was found between intracranial atherosclerotic stenosis and moderate-to-severe WMHs (P > 0.05). CONCLUSION:Carotid atherosclerotic plaque features, particularly presence of calcification, were independently associated with severity of WMHs, but such association was not found in intracranial atherosclerotic stenosis, suggesting that carotid atherosclerotic plaque characteristics may have closer association with severity of WMHs compared to intracranial atherosclerosis.

Background: Carotid atherosclerotic plaque inflammation plays a critical role in guiding the prevention of secondary stroke. Increased perivascular adipose tissue attenuation observed on computed tomography angiography (CTA) may indicate local inflammation. Our objective was to investigate whether pericarotid adipose tissue (PCAT), as a local inflammation biomarker, could distinguish between different stages of carotid atherosclerotic disease plaques.Methods: We prospectively enrolled 45 consecutive acute stroke patients with carotid artery stenosis from September 2019 to September 2021. We then matched them to non-stroke patients (n=67) and no carotid atherosclerotic disease controls (n=65) based on gender, age, and cardiovascular risk factors. We compared PCAT attenuation, carotid plaque features on CTA, clinical risk factors, and serum inflammatory factors across the different groups. To detect the association of PCAT attenuation with stage of carotid atherosclerotic disease, we used multivariable logistic regression analysis.Results: Patients with acute stroke had a higher PCAT attenuation (-78.80 +/- 11.62 HU) than patients with non-stroke (-89.01 +/- 10.81 HU, P<0.001) and no carotid atherosclerotic disease controls (-95.24 +/- 10.81 HU, P<0.001). PCAT attenuation was significantly increased in non-stroke patients compared to non-stroke patients over no carotid atherosclerotic disease controls (P=0.004). The association between PCAT attenuation and the stage of carotid atherosclerotic disease was independent of age, gender, cardiovascular risk factors, and CTA plaque characteristics. No interaction was observed between clinical features and CTA plaque characteristics on PCAT attenuation.Conclusions: PCAT attenuation, which is an imaging biomarker of local inflammation, independently distinguishes patients with different stages of carotid atherosclerotic disease. Quantitative evaluation of PCAT attenuation in carotid atherosclerotic disease is expected to guide targeted surgical treatment of carotid plaque.