Carotid artery perivascular adipose tissue on magnetic resonance imaging: a potential indicator for carotid vulnerable atherosclerotic plaque.

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.

Investigating the Association of Carotid Atherosclerotic Plaque MRI Features and Silent Stroke After Carotid Endarterectomy.

BACKGROUND: The predictive value of carotid plaque characteristics for silent stroke (SS) after carotid endarterectomy (CEA) is unclear. OBJECTIVE: To investigate the associations between carotid plaque characteristics and postoperative SS in patients undergoing CEA. STUDY TYPE: Prospective. POPULATION: One hundred fifty-three patients (mean age: 65.4 ± 7.9 years; 126 males) with unilateral moderate-to-severe carotid stenosis (evaluated by CT angiography) referred for CEA. FIELD STRENGTH/SEQUENCE: 3 T, brain-MRI:T2-PROPELLER, T1-/T2-FLAIR, diffusion weighted imaging (DWI) and T2*, carotid-MRI:black-blood T1-/T2W, 3D TOF, Simultaneous Non-contrast Angiography intraplaque hemorrhage. ASSESSMENT: Patients underwent carotid-MRI within 1-week before CEA, and brain-MRI within 48-hours pre-/post-CEA. The presence and size (volume, maximum-area-percentage) of carotid lipid-rich necrotic core (LRNC), intraplaque hemorrhage (Type-I/Type-II IPH) and calcification were evaluated on carotid-MR images. Postoperative SS was assessed from pre-/post-CEA brain DWI. Patients were divided into moderate-carotid-stenosis (50%-69%) and severe-carotid-stenosis (70%-99%) groups and the associations between carotid plaque characteristics and SS were analyzed. STATISTICAL TESTS: Independent t test, Mann-Whitney U-test, chi-square test and logistic regressions (OR: odds ratio, CI: confidence interval). P value <0.05 was considered statistically significant. RESULTS: SS was found in 8 (16.3%) of the 49 patients with moderate-carotid-stenosis and 21 (20.2%) of the 104 patients with severe-carotid-stenosis. In patients with severe-carotid-stenosis, those with SS had significantly higher IPH (66.7% vs. 39.8%) and Type-I IPH (66.7% vs. 38.6%) than those without. The presence of IPH (OR 3.030, 95% CI 1.106-8.305) and Type-I IPH (OR 3.187, 95% CI 1.162-8.745) was significantly associated with SS. After adjustment, the associations of SS with presence of IPH (OR 3.294, 95% CI 1.122-9.669) and Type-I IPH (OR 3.633, 95% CI 1.216-10.859) remained significant. Moreover, the volume of Type-II IPH (OR 1.014, 95% CI 1.001-1.028), and maximum-area-percentage of Type-II IPH (OR 1.070, 95% CI 1.002-1.142) and LRNC (OR 1.030, 95% CI 1.000-1.061) were significantly associated with SS after adjustment. No significant (P range: 0.203-0.980) associations were found between carotid plaque characteristics and SS in patients with moderate-carotid-stenosis. DATA CONCLUSIONS: In patients with unilateral severe-carotid-stenosis, carotid vulnerable plaque MR features, particularly presence and size of IPH, might be effective predictors for SS after CEA. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Perioperative cerebral blood flow measured by arterial spin labeling with different postlabeling delay in patients undergoing carotid endarterectomy: a comparison study with CT perfusion.

Background: Arterial spin labeling (ASL) is a non-invasive technique for measuring cerebral perfusion. Its accuracy is affected by the arterial transit time. This study aimed to (1) evaluate the accuracy of ASL in measuring the cerebral perfusion of patients who underwent carotid endarterectomy (CEA) and (2) determine a better postlabeling delay (PLD) for pre- and postoperative perfusion imaging between 1.5 and 2.0 s. Methods: A total of 24 patients scheduled for CEA due to severe carotid stenosis were included in this study. All patients underwent ASL with two PLDs (1.5 and 2.0 s) and computed tomography perfusion (CTP) before and after surgery. Cerebral blood flow (CBF) values were measured on the registered CBF images of ASL and CTP. The correlation in measuring perioperative relative CBF (rCBF) and difference ratio of CBF (DRCBF) between ASL with PLD of 1.5 s (ASL1.5) or 2.0 s (ASL2.0) and CTP were also determined. Results: There were no significant statistical differences in preoperative rCBF measurements between ASL1.5 and CTP (p = 0.17) and between ASL2.0 and CTP (p = 0.42). Similarly, no significant differences were found in rCBF between ASL1.5 and CTP (p = 0.59) and between ASL2.0 and CTP (p = 0.93) after CEA. The DRCBF measured by CTP was found to be marginally lower than that measured by ASL2.0_1.5 (p = 0.06) and significantly lower than that measured by ASL1.5_1.5 (p = 0.01), ASL2.0_2.0 (p = 0.03), and ASL1.5_2.0 (p = 0.007). There was a strong correlation in measuring perioperative rCBF and DRCBF between ASL and CTP (r = 0.67-0.85, p < 0.001). Using CTP as the reference standard, smaller bias can be achieved in measuring rCBF by ASL2.0 (-0.02) than ASL1.5 (-0.07) before CEA. In addition, the same bias (0.03) was obtained by ASL2.0 and ASL1.5 after CEA. The bias of ASL2.0_2.0 (0.31) and ASL2.0_1.5 (0.32) on DRCBF measurement was similar, and both were smaller than that of ASL1.5_1.5 (0.60) and ASL1.5_2.0 (0.60). Conclusion: Strong correlation can be found in assessing perioperative cerebral perfusion between ASL and CTP. During perioperative ASL imaging, the PLD of 2.0 s is better than 1.5 s for preoperative scan, and both 1.5 and 2.0 s are suitable for postoperative scan.

Reliability and Value of 3D Sequential QUantitative T1 -T2 -T2 * MAppings (SQUMA) MR Multi-Parametric Imaging in Characterizing Carotid Artery Atherosclerosis.

BACKGROUND: T1 , T2 , and T2 * mappings are seldom performed in a single examination, and their values in evaluating symptomatic atherosclerosis are lacking. PURPOSE: To perform three-dimensional (3D) quantitative T1 , T2 , and T2 * mappings (SQUMA) multi-parametric imaging for carotid vessel wall and evaluate its reliability and value in assessing carotid atherosclerosis. STUDY TYPE: Prospective. SUBJECTS: Eight healthy subjects and 20 patients with symptomatic carotid atherosclerosis. FIELD STRENGTH/SEQUENCE: 3 T, SQUMA imaging T1 -, T2 -, and T2 *-mapping, multi-contrast vessel wall imaging including T1 - and T2 -weighted, time-of-flight, and SNAP sequences. ASSESSMENT: SQUMA was acquired in all subjects and multi-contrast images were acquired in healthy subjects. T1 , T2 , and T2 * values and lumen area (LA), wall area (WA), mean wall thickness (MeanWT), and normalized wall index (NWI) of carotid arteries were measured. SQUMA and multi-contrast measurements were compared in healthy subjects and differences in SQUMA measurements between healthy subjects and patients were assessed. The discriminative value of SQUMA measurements for symptomatic vessel was determined. STATISTICAL TESTS: Paired t or Wilcoxon signed-rank test, independent t or Mann-Whitney U test, area under the receiver operating characteristic curve (AUC), intraclass correlation coefficients, and Bland-Altman plots. Statistically significant level, P < 0.05. RESULTS: There were no significant differences in LA (P = 0.340), WA (P = 0.317), MeanWT (P = 0.088), and NWI (P = 0.091) of carotid arteries between SQUMA and multi-contrast vessel wall images. The values of T2 (50.9 ± 2.9 msec vs. 44.5 ± 4.2 msec), T2 * (28.2 ± 4.3 msec vs. 24.7 ± 2.6 msec), WA (23.7 ± 4.6 mm2 vs. 36.2 ± 7.7 mm2 ), MeanWT (0.99 ± 0.05 mm vs. 1.50 ± 0.28 mm), and NWI (40.7 ± 3.0% vs. 53.8 ± 5.4%) of carotid arteries in healthy subjects were significantly different from those in atherosclerotic patients. The combination of quantitative T1 , T2 , and T2 * values and MeanWT showed greatest AUC (0.81; 95% CI: 0.65-0.92) in discriminating symptomatic vessels. DATA CONCLUSION: Carotid MR 3D quantitative multi-parametric imaging of SQUMA enables acquisition of T1 , T2 , and T2 * maps, reliably measuring carotid morphology and discriminating carotid symptomatic atherosclerosis. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Segmentation and differentiation of periventricular and deep white matter hyperintensities in 2D T2-FLAIR MRI based on a cascade U-net.

Background: White matter hyperintensities (WMHs) are a subtype of cerebral small vessel disease and can be divided into periventricular WMHs (pvWMHs) and deep WMHs (dWMHs). pvWMHs and dWMHs were proved to be determined by different etiologies. This study aimed to develop a 2D Cascade U-net (Cascade U) for the segmentation and differentiation of pvWMHs and dWMHs on 2D T2-FLAIR images. Methods: A total of 253 subjects were recruited in the present study. All subjects underwent 2D T2-FLAIR scan on a 3.0 Tesla MR scanner. Both contours of pvWMHs and dWMHs were manually delineated by the observers and considered as the gold standard. Fazekas scale was used to evaluate the burdens of pvWMHs and dWMHs, respectively. Cascade U consisted of a segmentation U-net and a differentiation U-net and was trained with a combined loss function. The performance of Cascade U was compared with two other U-net models (Pipeline U and Separate U). Dice similarity coefficient (DSC), Matthews correlation coefficient (MCC), precision, and recall were used to evaluate the performances of all models. The linear correlations between WMHs volume (WMHV) measured by all models and the gold standard were also conducted. Results: Compared with other models, Cascade U exhibited a better performance on WMHs segmentation and pvWMHs identification. Cascade U achieved DSC values of 0.605 ± 0.135, 0.517 ± 0.263, and 0.510 ± 0.241 and MCC values of 0.617 ± 0.122, 0.526 ± 0.263, and 0.522 ± 0.243 on the segmentation of total WMHs, pvWMHs, and dWMHs, respectively. Cascade U exhibited strong correlations with the gold standard on measuring WMHV (R2 = 0.954, p < 0.001), pvWMHV (R2 = 0.933, p < 0.001), and dWMHV (R2 = 0.918, p < 0.001). A significant correlation was found on lesion volume between Cascade U and gold standard (r > 0.510, p < 0.001). Conclusion: Cascade U showed competitive results in segmentation and differentiation of pvWMHs and dWMHs on 2D T2-FLAIR images, indicating potential feasibility in precisely evaluating the burdens of WMHs.

Slice-based and time-specific hemodynamic measurements discriminate carotid artery vulnerable atherosclerotic plaques.

BACKGROUND AND OBJECTIVE: Hemodynamic patterns play key roles in progression of carotid vulnerable plaques. However, most of previous studies utilized maximum or averaged value of hemodynamic measurements which is not an ideal representative of hemodynamic patterns. This study aimed to investigate the association of slice-based and time-specific hemodynamic measurements with carotid vulnerable plaque using magnetic resonance (MR) vessel wall imaging and histology. METHODS: Thirty-two patients (mean age: 63.9±8.1 years; 25 males) with carotid atherosclerotic stenosis (≥50% stenosis) referred to carotid endarterectomy were recruited and underwent MR vessel wall imaging. Carotid plaque burden was evaluated on MR images and vulnerable plaque features including calcification, lipid-rich necrotic core, and intra-plaque hemorrhage (IPH) were identified by histology. The slice-based and time-specific hemodynamic measurements were extracted from computational fluid dynamics simulation of 3D carotid arterial model. Correlation coefficients between hemodynamic measurements and carotid plaque features were calculated and the logistic regressions with generalized estimating equation (GEE) were conducted. The value in discriminating carotid vulnerable plaque features was determined by receiver-operating-characteristic analysis. RESULTS: Of 102 MR-histology matched slices from 32 patients, time-averaged wall shear stress (TAWSS) (r=0.263, p=0.008), oscillatory shear index (OSI) (r=-0.374, p<0.001), and peakWSS (r=0.232, p=0.019) were significantly associated with carotid IPH. The logistic regression with GEE revealed that peakWSS (OR, 1.206; 95% CI, 1.026-1.418; p, 0.023) and TAWSS (OR, 0.364, 95% CI, 0.138-0.959; p, 0.041) were significantly associated with presence of IPH after adjusting for age and BMI. In discriminating carotid IPH, the AUC of TAWSS, OSI, combined TAWSS with maximum wall thickness (MWT) and combined OSI with MWT was 0.656, 0.722, 0.761, and 0.764, respectively. CONCLUSIONS: Slice-based and time-specific hemodynamic characteristics could effectively discriminate carotid IPH. Combination of hemodynamic measurements with carotid plaque burden might be a stronger indicator for carotid vulnerable plaque features than each measurement alone.

Associations between cerebral blood flow and progression of white matter hyperintensity in community-dwelling adults: a longitudinal cohort study.

Background: White matter hyperintensity (WMH) is prevalent in elderly populations. Ischemia is characterized by a decline in cerebral blood flow (CBF) and may play a key role in the pathogenesis of WMH. However, the association between CBF reduction and WMH progression remains controversial. This study aimed to investigate the association between CBF and the progression of WMH at a 2-year follow-up of community-based, asymptomatic adults in a longitudinal cohort study across the lifespan. Methods: Asymptomatic adults who participated in a community-based study were recruited and underwent brain structural and perfusion magnetic resonance imaging (MRI) at baseline and at a 2-year follow-up visit. The CBF was measured on pseudo-continuous arterial spin-labeling (pCASL) MRI. The WMH was evaluated on T2-weighted fluid-attenuated inversion recovery (T2-FLAIR) images. Tissue segmentation was conducted on T1-weighted (T1W) images to derive binary masks of gray matter and normal-appearing white matter. Linear mixed effect models were conducted to analyze the cross-sectional and longitudinal associations between CBF and WMH. Results: A total of 229 adults (mean age 57.3±12.6 years; 94 males) were enrolled at baseline, among whom 84 participants (mean age 54.1±11.9 years; 41 males) completed a follow-up visit with a mean time interval of 2.77±0.44 years. At baseline, there was a decreasing trend in gray matter (GM) CBF with an increase of WMH burden (P=0.063), but this association was attenuated after adjusting for age (P=0.362). In the longitudinal analysis, baseline WMH volume was significantly associated with the reduction of perfusion in GM [coefficient =-1.96, 95% confidence interval (CI): -3.25 to -0.67; P=0.004] and normal appearing white matter (coefficient =-0.99, 95% CI: -1.66 to -0.31; P=0.005) during follow-up. On the contrary, neither baseline CBF in GM (P=0.888) nor normal appearing white matter (P=0.850) was associated with WMH progression. In addition, CBF changes within WMH were significantly associated with both baseline (coefficient =-0.014, 95% CI: -0.025 to -0.003; P=0.017) and progression (coefficient =-1.01, 95% CI: -1.81 to -0.20; P=0.015) of WMH volume. Conclusions: A WMH burden was not found to be directly associated with cortex perfusion at baseline due to the effects of age on both CBF and WMH. However, baseline WMH volume could predict the reduction of perfusion.

Association between antiplatelet medication and cerebral microbleeds in stroke-free population.

BACKGROUND: Cerebral microbleeds (CMBs) may increase the risk of future intracerebral hemorrhage and ischemic stroke. However, It is unclear whether antiplatelet medication is associated with CMBs. This study aimed to investigate the association between antiplatelet medication and CMBs in a community-based stroke-free population. METHODS: In this cross-sectional study, stroke-free participants aged 18-85 years were recruited from a community in Beijing, China. Demographic, clinical, and antiplatelet medication data were collected through a questionnaire, and all participants underwent blood tests and brain magnetic resonance imaging at 3.0T. The presence, count, and location of CMBs were evaluated using susceptibility-weighted imaging. The association between antiplatelet medication and the presence of CMBs was analyzed using multivariable logistic regression. The associations between antiplatelet medication and CMBs by location (lobar, deep brain or infratentorial, and mixed regions) were also analyzed using multinomial logistic regression. A linear regression analysis was conducted to determine the association between antiplatelet medication and the log-transformed number of CMBs. RESULTS: Of the 544 participants (mean age: 58.65 ± 13.66 years, 217 males), 119 participants (21.88%) had CMBs, and 64 participants (11.76%) used antiplatelet medication. Antiplatelet medication was found to be associated with CMBs at any location [odds ratio (OR) = 2.39, 95% CI: 1.24-4.58] and lobar region (OR = 2.83, 95% CI: 1.36-5.86), but not with the number of CMBs (ß = 0.14, 95% CI: -0.21-0.48). Among antiplatelet medications, aspirin use was found to be associated with any CMB (OR = 3.17, 95% CI: 1.49-6.72) and lobar CMBs (OR = 3.61, 95% CI: 1.57-8.26). CONCLUSIONS: Antiplatelet medication was associated with CMBs in stroke-free participants, particularly lobar CMBs. Among antiplatelet medications, aspirin use was associated with any CMB and lobar CMBs. Our findings suggest that it might be essential to optimize the management of antiplatelet medication in the stroke-free population with a higher burden of vascular risk factors to reduce the potential risk of CMBs.

Association between haemoglobin A1c and cerebral microbleeds in community-based stroke-free individuals: A cross-sectional study.

AIMS: The association between haemoglobin A1c (HbA1c) and cerebral microbleeds (CMBs) remains unclear. We aimed to investigate the association between HbA1c and CMBs in community-based individuals without stroke or transient ischaemic attack (TIA) and whether the association differs between individuals with and without diabetes mellitus (DM). MATERIALS AND METHODS: All individuals were recruited from a community in Beijing, China, from January 2015 to September 2019. All individuals completed a questionnaire and underwent blood tests and brain magnetic resonance imaging. A susceptibility-weighted imaging sequence was acquired to detect CMBs, which were defined as small, round and low-signal lesions with <10 mm diameter. The association between HbA1c and CMBs was analysed using multivariable logistic regression adjusted for demographics, medical history and blood sample test results. Subgroup analyses stratified by history of DM were performed. RESULTS: Of 544 recruited individuals, 119 (21.88%) had CMBs. HbA1c was independently associated with CMBs (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.03-2.22). In 87 individuals with DM, multivariable logistic analysis showed that HbA1c was significantly associated with CMBs (OR, 1.67; 95% CI, 1.04-2.69), whereas in individuals without DM, no significant association was observed between HbA1c and CMBs (OR, 1.07; 95% CI, 0.50-2.30). CONCLUSIONS: HbA1c was associated with CMBs in individuals without stroke or TIA, particularly in individuals with DM, suggesting that the status of glycaemic control warrants attention for the prevention of CMBs. It would be beneficial to manage HbA1c specifically to control the risk of CMBs, especially in individuals with DM.

Saturated multi-delay renal arterial spin labeling technique for simultaneous perfusion and T1 quantification in kidneys.

PURPOSE: To propose a free-breathing simultaneous multi-delay arterial spin labeling (ASL) and T1 mapping technique with a stepwise kinetic model for renal assessment in a single 4-min scan at 3 T. METHODS: The proposed saturated multi-delay renal arterial spin labeling (SAMURAI) sequence used flow-sensitive alternating inversion recovery (FAIR) preparation, followed by acquisition of 9 images with Look-Locker spoiled gradient recalled echo (SPGR). Pre-saturation at the imaging slice was used to achieve saturation-based T1 mapping. A 4-step 2-compartment kinetic model was proposed to characterize water transition through artery- and tissue-compartment. The impact of the Look-Locker sampling scheme on the ASL signal was corrected in this model. T1 estimation with dictionary searching method and perfusion quantification based on the proposed kinetic model fitting were conducted after groupwise registration of the acquired images. The feasibility and repeatability of SAMURAI were validated in healthy subjects (n = 11) and patients with different renal diseases (n = 4). RESULTS: The proposed SAMURAI technique can provide accurate T1 map with strong correlation (R2  = 0.98) with inversion recovery spin echo (IR-SE) on phantom. SAMURAI provided equally reliable whole kidney and cortical ASL and T1 quantification results compared with multi-TI FAIR (intraclass correlation coefficient [ICC], 0.880-0.958) and IR-SPGR (ICC, 0.875-0.912), respectively. Low renal blood flow and increased T1 were detected by SAMURAI in the affected kidneys of the patients. SAMURAI had excellent scan-rescan repeatability (ICC, 0.905-0.992) and significantly reduced scan time (4 min 6 s vs. 45 min for 9 TIs) compared to multi-TI FAIR. CONCLUSION: The proposed SAMURAI technique is feasible and repeatable for simultaneously quantifying T1 and perfusion of kidneys with high time-efficiency.

Longitudinal Changes in Global Cerebral Blood Flow in Cognitively Normal Older Adults: A Phase-Contrast MRI Study.

BACKGROUND: Characterization of blood supply changes in older individuals is important in understanding brain aging and diseases. However, prior studies largely focused on cross-sectional design, thus change in cerebral blood flow (CBF) could not be assessed on an individual level. PURPOSE: To evaluate longitudinal short-term changes in global CBF in cognitively normal older adults. STUDY TYPE: Prospective, longitudinal, and cohort. POPULATION: One-hundred twenty-seven cognitive-normal participants (mean age 69 ± 7 years, 47 males) underwent serial MRI with an average follow-up time of 2.1 years. FIELD STRENGTH/SEQUENCE: 3 T phase-contrast (PC), three-dimensional magnetization-prepared-rapid-acquisition-of-gradient-echo (MPRAGE) and fluid-attenuated inversion recovery (FLAIR) MRI. ASSESSMENT: Total CBF was measured with PC MRI allowing assessment of quantitative flow in four major feeding arteries by a trained radiologist with >3 years' experience (O.K.). Brain volume was obtained from MPRAGE MRI and measured by T1-MultiAtlas MRICloud tool. The ratio between total CBF and brain volume yielded global CBF in mL/100 g/min. White matter hyperintensity (WMH) was measured automatically using a Bayesian probability approach on FLAIR. STATISTICAL TESTS: Linear mixed effect model was used to simultaneously assess cross-sectional age-differences and longitudinal age-changes in CBF. Spearman rank correlation was used to evaluate the relationship between CBF change and WMH progression. A P-value of <0.05 (two-tailed) was considered significant. RESULTS: Global CBF decreased with age at a longitudinal rate of -0.56 mL/100 g/min/year (95% confidence interval [CI]: -1.09, -0.03), compared to a cross-sectional rate of -0.26 mL/100 g/min/year (95% CI: -0.41, -0.11). Changes in CBF were significantly associated with progression of WMH (Spearman rank correlation r = -0.25), as those participants who had a more rapid CBF reduction had greater increases in WMH volumes and the relationship remained significant when adjusting for baseline vascular risk scores. Additionally, age-related changes in whole-brain volume were found to be -0.151%/year (95% CI: -0.186, -0.116). DATA CONCLUSION: These findings suggest that brain aging in older adults is accompanied by a rapid longitudinal reduction in CBF, the rate of which is associated with white matter damage. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Risk Factors for Asymptomatic and Symptomatic Intracranial Atherosclerosis Determined by Magnetic Resonance Vessel Wall Imaging in Chinese Population: A Case-Control Study.

BACKGROUND AND PURPOSE: The association between risk factors and intracranial atherosclerosis disease (ICAD) determined by magnetic resonance (MR) vessel wall imaging in Chinese population has not been investigated. The aim of this study was to investigate the associations of conventional vascular risk factors with asymptomatic and symptomatic ICAD using MR vessel wall imaging in Chinese population. METHODS: The study population was recruited from two cohort studies of ICASMAP and CAMERA comprised 104 symptomatic ICAD subjects (57.1 ± 11.1 years; 35.6% females), 51 asymptomatic ICAD subjects (70.1 ± 8.4 years; 50.0% females) and 418 controls (58.0 ± 13.3 years; 61.0% females) defined as asymptomatic subjects without ICAD on MR vessel wall imaging. We compared the vascular risk factors between the three groups using a multivariate logistic regression analysis. RESULTS: Compared with controls, there was a significant positive association between age (OR: 1.07, 95% CI: 1.03-1.10, p < 0.001) and hypertension (OR: 3.03, 95% CI: 1.45-6.36, p = 0.003) and asymptomatic ICAD. There was a positive association of smoking (OR: 3.41, 95% CI: 1.57-7.42, p = 0.001), hypertension (OR: 7.43, 95% CI: 3.81-14.49, p < 0.001) and diabetes (OR: 3.54, 95% CI: 1.93-6.49, p < 0.001) and an inverse association of high-density lipoprotein (HDL) (p < 0.017) with symptomatic ICAD. Compared to asymptomatic ICAD, there was a significant inverse association of age (OR: 0.86, 95% CI: 0.81-0.92, p < 0.001) and HDL (p < 0.001) with symptomatic ICAD. CONCLUSION: Old age and hypertension are associated with asymptomatic ICAD and smoking, hypertension, diabetes and lower HDL are associated with an increased risk of symptomatic ICAD in Chinese population. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03417063.

Free-breathing three-dimensional isotropic-resolution MR sequence for simultaneous vessel wall imaging of bilateral renal arteries and abdominal aorta: Feasibility and reproducibility.

PURPOSE: Many diseases can simultaneously involve renal arteries and the adjacent abdominal aorta. This study proposed a free-breathing three-dimensional (3D) isotropic-resolution magnetic resonance sequence for simultaneous vessel wall imaging (VWI) of bilateral renal arteries and adjacent abdominal aorta. METHODS: A respiratory-triggered isotropic-resolution sequence that combined the improved motion-sensitized driven-equilibrium (iMSDE) preparation with the spoiled gradient recalled (SPGR) readout (iMSDE-SPGR) was proposed for simultaneous VWI of renal arteries and abdominal aorta. The proposed iMSDE-SPGR sequence was optimized by positioning spatial saturation pulses (i.e., REST slabs) elaborately to further alleviate respiratory and gastrointestinal motion artifacts and selecting appropriate first-order gradient moment (m1 ) of the iMSDE preparation. Thirteen healthy subjects and 13 patients with renal artery stenosis underwent simultaneous VWI with the optimized iMSDE-SPGR sequence at 3.0 T. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and morphology of renal arterial wall and aortic wall were measured. Reproducibility of intra-observer, inter-observer, and scan-rescan (n = 13 healthy subjects) in measuring SNR, CNR, and morphology was evaluated. For the reproducibility test, the agreement was determined using intraclass correlation coefficients (ICC), and the differences were compared using paired t-test or nonparametric Wilcoxon test when appropriate. Bland-Altman plots were used to calculate the bias between observers and between scans. RESULTS: The proposed iMSDE-SPGR sequence was feasible for simultaneous VWI both in the healthy subjects and the patients. The sequence showed good to excellent inter-observer (ICC: 0.615-0.999), excellent intra-observer (ICC: 0.801-0.998), and scan-rescan (ICC: 0.768-0.998) reproducibility in measuring morphology, SNR, and CNR. There were no significant differences in SNR, CNR, and morphology measurements between observers and between scans (all p > 0.05). Bland-Altman plots showed small bias in assessing SNR, CNR, and morphology. DATA CONCLUSION: The proposed free-breathing 3D isotropic-resolution iMSDE-SPGR technique is feasible and reproducible for simultaneous VWI of bilateral renal arteries and adjacent abdominal aorta.

Comparing Symptomatic and Asymptomatic Carotid Artery Atherosclerosis in Patients With Bilateral Carotid Vulnerable Plaques Using Magnetic Resonance Imaging.

We compared plaque characteristics between symptomatic and asymptomatic sides in patients with bilateral carotid vulnerable plaques using magnetic resonance imaging (MRI). Participants (n = 67; mean age: 65.8 ± 7.7 years, 61 males) with bilateral carotid vulnerable plaques were included. Vulnerable plaques were characterized by intraplaque hemorrhage (IPH), large lipid-rich necrotic core (LRNC), or fibrous cap rupture (FCR) on MRI. Symptomatic vulnerable plaques showed greater plaque burden, LRNC volume (median: 221.4 vs 134.8 mm3, P = .003), IPH volume (median: 32.2 vs 22.5 mm3, P = .030), maximum percentage (Max%) LRNC (median: 51.3% vs 41.8%, P = .002), Max%IPH (median: 13.4% vs 9.5%, P = .022), cumulative slices of LRNC (median: 10 vs 8, P = .005), and more juxtaluminal IPH and/or thrombus (29.9% vs 6.0%, P = .001) and FCR (37.3% vs 16.4%, P = .007) than asymptomatic ones. After adjusting for plaque burden, differences in juxtaluminal IPH and/or thrombus (odds ratio [OR]: 5.49, 95% CI: 1.61-18.75, P = .007) and FCR (OR: 2.90, 95% CI: 1.16-7.24, P = .022) between bilateral sides remained statistically significant. For patients with bilateral carotid vulnerable plaques, symptomatic plaques had greater burden, more juxtaluminal IPH and/or thrombus, and FCR compared with asymptomatic ones. The differences in juxtaluminal IPH and/or thrombus and FCR between bilateral sides were independent of plaque burden.

Evaluating renal arterial wall by non-enhanced 2D and 3D free-breathing black-blood techniques: Initial experience.

OBJECTIVES: To evaluate the feasibility and reproducibility of 2D and 3D black-blood sequences in measuring morphology of renal arterial wall. METHODS: The 2D and 3D imaging sequences used variable-refocusing-flip-angle and constant-low-refocusing-flip-angle turbo spin echo (TSE) readout respectively, with delicately selected black-blood scheme and respiratory motion trigger for free-breathing imaging. Fourteen healthy subjects and three patients with Takayasu arteritis underwent renal artery wall imaging with 3D double inversion recovery (DIR) TSE and 2D Variable Flip Angle-TSE (VFA-TSE) black-blood sequences at 3.0 T. Four healthy subjects were randomly selected for scan-rescan reproducibility experiments. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and morphology of arterial wall were measured and compared using paired-t-test or Wilcoxon signed-rank test between 2D and 3D sequences. The inter-observer, intra-observer and scan-rescan agreements of above measurements were determined using intraclass correlation coefficient (ICC). RESULTS: The 2D and 3D imaging sequences showed similar morphological measurements (lumen area, wall area, mean wall thickness and maximum wall thickness) of renal arterial wall (all P > 0.05) and excellent agreement (ICC: 0.853-0.954). Compared to 2D imaging, 3D imaging exhibited significantly lower SNRlumen (P < 0.01) and SNRwall (P = 0.037), similar contrast-to-noise ratio (CNR) (P = 0.285), and higher CNR efficiency (CNReff) (P < 0.01). Both 2D and 3D imaging showed good to excellent inter-observer (ICC: 0.723-0.997), intra-observer (ICC: 0.749-0.996) and scan-rescan (ICC: 0.710-0.992) reproducibility in measuring renal arterial wall morphology, SNR and CNR, respectively. CONCLUSIONS: Both high-resolution free-breathing 2D VFA-TSE and 3D DIR TSE black-blood sequences are feasible and reproducible in high-resolution renal arterial wall imaging. The 2D imaging has high SNR, whereas 3D imaging has high imaging efficiency.

Histological validation of simultaneous non-contrast angiography and intraplaque hemorrhage imaging (SNAP) for characterizing carotid intraplaque hemorrhage.

OBJECTIVES: This study sought to validate the performance of simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP) imaging in characterizing carotid IPH by histology. METHODS: Thirty-five patients with carotid atherosclerotic disease (symptomatic 50-70% stenosis or > 70% stenosis) scheduled for carotid endarterectomy underwent 3.0-T carotid MR imaging by acquiring SNAP and magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) sequences. Presence and area of IPH were separately evaluated on SNAP and MP-RAGE images. Presence and area of IPH were also assessed on histology. Agreement between SNAP/MP-RAGE and histology was determined in identify and quantify IPH using Cohen kappa, Spearman correlation, and Bland-Altman analyses. RESULTS: Of all 35 patients (mean age: 63.1 ± 8.8 years; 27 males), 128 slices with successful registration were eligible for analysis. The accuracy, sensitivity, specificity, and positive and negative predictive values were 86.7%, 85%, 89.6%, 93.2%, and 78.2% for SNAP, and 76.6%, 75%, 79.2%, 85.7%, and 65.5% for MP-RAGE in identification of IPH, respectively. In identification of IPH, the kappa value between SNAP and histology and between MP-RAGE and histology was 0.725 and 0.520, respectively. The correlation between SNAP and histology (r = 0.805, p < 0.001) was stronger than that between MP-RAGE and histology (r = 0.637, p < 0.001) in measuring IPH area. Bland-Altman analysis showed that, in measuring IPH area, the bias of SNAP (1.4 mm2, 95% CI: - 0.016 to 2.883) was smaller than that of MP-RAGE (1.7 mm2, 95% CI: - 0.039 to 3.430) compared with histology. CONCLUSIONS: This validation study by histology demonstrates that SNAP sequence better identifies and quantifies carotid intraplaque hemorrhage compared with traditional MP-RAGE sequence. KEY POINTS: • SNAP imaging showed better agreement with histology compared with MP-RAGE imaging, especially for the IPHs with small size. • SNAP sequence is a more effective tool to identify and quantify carotid IPH than traditional sequence of MP-RAGE that can help clinicians to optimizing the treatment strategy. • The plaque components of rich lipid pools or loose matrix and chronic/old IPH (cholesterol crystals) can lead to false positive and false negative results in SNAP and MP-RAGE imaging for identifying IPH.

Associations Between Carotid Plaque Characteristics and Improvement of Cerebral Blood Perfusion in Patients With Moderate to Severe Carotid Stenosis Undergoing Carotid Endarterectomy.

BACKGROUND: The relationship between plaque characteristics and their predictive value for perioperative cerebral blood flow (CBF) are unknown. PURPOSE: To investigate the relationship between carotid plaque characteristics and perioperative CBF utilizing MRI. STUDY TYPE: Prospective. POPULATION: In all, 131 patients with carotid moderate-to-severe stenosis referred for carotid endarterectomy (CEA). FIELD STRENGTH/SEQUENCE: 3T, black-blood T1 - and T2 -weighted, 3D time-of-flight, and simultaneous noncontrast angiography intraplaque hemorrhage. ASSESSMENT: The relative CBF (rCBF = CBFindex-hemisphere /CBFcontralateral-hemisphere ) and the CBF difference ratio (DRCBF = [CBFpost-CEA - CBFpre-CEA ]/CBFpre-CEA ) in the middle cerebral artery territory were measured. The pre- and post-CEA CTP data were used as the assessment standard for CBF change. Carotid lipid-rich necrotic core (LRNC), intraplaque hemorrhage, calcification, fibrous cap rupture, maximum wall thickness, normalized wall index (NWI), and stenosis were determined. STATISTICAL TESTS: Pearson or Spearman correlation, Mann-Whitney U-test, and linear regression. RESULTS: Patients with LRNC had higher rCBFpre-CEA than those without (1.0 ± 0.1 vs. 0.9 ± 0.1, P < 0.05). NWI was weakly correlated with rCBFpre-CEA (r = -0.213, P < 0.05) and DRCBF (r = 0.185, P < 0.05) and marginally correlated with rCBFpost-CEA (r = 0.166, P = 0.057). LRNC was weakly correlated with rCBFpre-CEA (r = 0.179, P < 0.05). NWI was associated with rCBFpre-CEA (ß = -0.035; 95% confidence interval [CI] [-0.064, -0.006]; P < 0.05), rCBFpost-CEA (ß = 0.042; 95% CI [0.002, 0.081]; P < 0.05) and DRCBF (ß = 0.105; 95% CI [0.026, 0.185]; P < 0.05). After adjusting for confounding factors, associations of NWI with rCBFpost-CEA (ß = 0.059; 95% CI [0.016, 0.103]; P < 0.05) and DRCBF (ß = 0.110; 95% CI [0.021, 0.199]; P < 0.05) remained statistically significant, while the association between NWI and rCBFpre-CEA was no longer significant (ß = -0.026; 95% CI [-0.058, 0.006]; P = 0.112).The associations of LRNC with rCBFpre-CEA (ß = 0.057; 95% CI [-0.0006, 0.114]; P = 0.052) and DRCBF (ß = -0.157; 95% CI [-0.314, 0.001]; P = 0.051) were close to statistical significance. After adjusting for confounding factors, these associations were statistically significant (of LRNC vs. rCBFpre-CEA : ß = 0.060; 95% CI [0.003, 0.118]; P < 0.05; LRNC vs. DRCBF : ß = -0.205; 95% CI [-0.375, -0.036]; P < 0.05). DATA CONCLUSION: Carotid plaque burden and components, particularly LRNC, might be effective indicators for CBF change following CEA. Level of Evidence 1 Technical Efficacy Stage 5.

Quantitative evaluation of carotid atherosclerotic vulnerable plaques using in vivo T1 mapping cardiovascular magnetic resonaonce: validation by histology.

BACKGROUND: It has been proved that multi-contrast cardiovascular magnetic resonance (CMR) vessel wall imaging could be used to characterize carotid vulnerable plaque components according to the signal intensity on different contrast images. The signal intensity of plaque components is mainly dependent on the values of T1 and T2 relaxation. T1 mapping recently showed a potential in identifying plaque components but it is not well validated by histology. This study aimed to validate the usefulness of in vivo T1 mapping in assessing carotid vulnerable plaque components by histology. METHODS: Thirty-four subjects (mean age, 64.0 ± 8.9 years; 26 males) with carotid plaques referred to carotid endarterectomy were prospectively enrolled and underwent 3 T CMR imaging from May 2017 to October 2017. The T1 values of intraplaque hemorrhage (IPH), necrotic core (NC) and loose matrix (LM) which were identified on multi-contrast vessel wall images or histology were measured on in-vivo T1 mapping. The IPHs were divided into two types based on the proportion of the area of fresh hemorrhage on histology. The T1 values of different plaque components were compared using Mann-Whitney U test and the agreement between T1 mapping and histology in identifying and quantifying IPH was analyzed with Cohen's Kappa and intraclass correlation coefficient (ICC). RESULTS: Of 34 subjects, 19 had histological specimens matched with CMR imaging. The mean T1 values of IPH (651 ± 253 ms), NC (1161 ± 182 ms) and LM (1447 ± 310 ms) identified by histology were significantly different. The T1 values of Type 1 IPH were significantly shorter than that of Type 2 IPH (456 ± 193 ms vs. 775 ± 205 ms, p < 0.001). Moderate to excellent agreement was found in identification (kappa = 0.51, p < 0.001), classification (kappa = 0.40, p = 0.028) and segmentation (ICC = 0.816, 95% CI 0.679-0.894) of IPHs between T1 mapping and histology. CONCLUSIONS: The T1 values of carotid plaque components, particularly for intraplaque hemorrhage, are differentiable, and the stage of intraplaque hemorrhage can be classified according to T1 values, suggesting the potential capability of assessment of vulnerable plaque components by T1 mapping.

Intracranial simultaneous noncontrast angiography and intraplaque hemorrhage (SNAP) MRA: Analyzation, optimization, and extension for dynamic MRA.

PURPOSE: Simultaneous noncontrast angiography and intraplaque (SNAP) imaging, as a noncontrast-enhanced MRA technique, may not provide consistent vessel visualization for intracranial artery imaging among subjects. This study aims to investigate the underlying mechanism and extend SNAP to dynamic MRA. METHODS: The cause of the instability of intracranial SNAP-MRA was investigated through theoretical analysis and simulations. The scan parameters, including TI and flip angle, were optimized for reliable imaging. In vivo experiments were conducted to validate the simulation results. The simulation results were correlated with real intracranial blood flow by introducing the concept of blood travel time, and intracranial SNAP-MRA was revealed to reflect the cerebral blood expanse region in 5 TI. A new noncontrast-enhanced dynamic MRA technique, termed 4D SNAP-MRA, was proposed and demonstrated through in vivo scans. RESULTS: The cause of the instability of intracranial SNAP-MRA was proved to be the slow or fast blood flow in the imaging slab. This instability can be mitigated by adjusting TI and flip angle in the SNAP sequence. The proposed 4D SNAP-MRA can provide dynamic visualization of the cerebral blood circulation and cerebral hemodynamic information such as blood travel time. CONCLUSION: The 3D SNAP-MRA with optimal imaging parameters can generate cerebral angiography with hemodynamic information, and the 4D SNAP-MRA provides dynamic visualization of the cerebral blood circulation.

Reduction of cerebral blood flow in community-based adults with subclinical cerebrovascular atherosclerosis: A 3.0T magnetic resonance imaging study.

Reduction in cerebral blood flow (CBF), one of the major metrics for cerebral perfusion, is associated with many brain disorders. Therefore, early characterization of CBF prior to occurrence of symptoms is essential for prevention of cerebral ischemic events. We hypothesized that large artery atherosclerosis might be a potential indicator for decline in cerebral perfusion. The aim of this study was to investigate the relationship between large artery atherosclerosis and CBF in asymptomatic adults. A total of 134 asymptomatic subjects (mean age, 56.2 ±â€¯12.8 years; 54 males) were recruited and underwent magnetic resonance (MR) imaging for brain and intracranial and extracranial carotid arteries. Presence or absence of cerebrovascular atherosclerosis was determined on MR vessel wall images. The CBF was measured with pseudo-continuous arterial spin labeling (pCASL) imaging. The CBF values in internal carotid artery (ICA) (37.2 ±â€¯5.8 vs. 39.0 ±â€¯4.9 ml/100 g/min, P = 0.049) and vertebrobasilar artery (VA-BA) territories (42.0 ±â€¯6.8 vs. 44.8 ±â€¯7.0 ml/100 g/min, P = 0.023) were significantly reduced in subjects with cerebrovascular plaque compared to those without. Presence of cerebrovascular plaque was significantly associated with CBF of VA-BA territory before (odds ratio, 2.89; 95% confidence interval, 1.37-6.08; P = 0.005) and after adjusted for confounding factors including age, gender, body-mass-index, diabetes, systolic blood pressure, hyperlipidemia and history of cardiovascular disease (odds ratio, 2.76; 95% confidence interval, 1.18-6.46; P = 0.019). In conclusion, presence of cerebrovascular atherosclerosis is independently associated with reduction in CBF measured by pCASL in asymptomatic adults, suggesting that cerebrovascular large artery atherosclerosis might be an effective indicator for impairment of cerebral microcirculation hemodynamics.