Carotid atherosclerotic plaque predicts progression of intracranial artery atherosclerosis: A MR imaging-based community cohort study.

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.

Atherosclerotic plaque characteristics in extracranial carotid artery may indicate closer association with white matter hyperintensities than intracranial arteries: A CARE-II study.

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.

Pericarotid adipose tissue computed tomography attenuation distinguishes different stages of carotid atherosclerotic disease: a cross-sectional study.

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.

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.

Simultaneous T1, T2, and T2* Mapping of Carotid Plaque: The SIMPLE* Technique.

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.

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.

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.

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.

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.

Co-existing Hypertension and Hyperhomocysteinemia Increases the Risk of Carotid Vulnerable Plaque and Subsequent Vascular Event: An MR Vessel Wall Imaging Study.

Purpose: This study sought to determine the associations of co-existing hypertension and hyperhomocysteinemia (H-Hcy) with carotid vulnerable plaque features and subsequent vascular events. Methods: Symptomatic patients with carotid atherosclerosis were enrolled and underwent carotid magnetic resonance (MR) vessel wall imaging. The patients were divided into the following groups: co-existing hypertension and H-Hcy group; isolated hypertension group; isolated H-Hcy group; and control group. The morphological and compositional characteristics of carotid plaques were assessed on MR images and compared among different groups. Univariate and multivariate cox regressions were used to calculate the hazard ratio (HR) and corresponding 95% confidence interval (CI) of co-existing hypertension and H-Hcy in predicting subsequent vascular events after at least 1-year followed-up. Results: In total, 217 patients (mean age, 59.4 ± 11.9 years; 154 males) were recruited. Patients in co-existing hypertension and H-Hcy group had a significantly higher prevalence of carotid lipid-rich necrotic core (LRNC) than isolated H-Hcy and control group (73.2 vs. 43.3 vs. 50%, p = 0.015). During the median follow-up time of 12.2 ± 4.3 months, 61 (39.8%) patients experienced vascular events. After adjusting for baseline confounding factors, co-existing hypertension and H-Hcy (HR, 1.82; 95% CI, 1.01-3.27; p = 0.044), presence of carotid LRNC (HR, 2.25; 95% CI, 1.09-4.65; p = 0.029), and combination of co-existing hypertension and H-Hcy and carotid LRNC (HR, 2.39; 95% CI, 1.26-4.43; p = 0.007) were significantly associated with subsequent vascular events. Conclusions: Co-existing hypertension and H-Hcy are associated with carotid vulnerable plaque features, such as LRNC. Combining co-existing hypertension and H-Hcy with carotid vulnerable plaque features has a stronger predictive value for subsequent vascular events than each measurement alone.

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.

A comparison of carotid atherosclerosis in symptomatic patients between 2002-2005 and 2012-2015 cohorts using multi-contrast magnetic resonance vessel wall imaging.

OBJECTIVE: To compare the morphological and compositional characteristics of carotid plaques in two cohorts (2002-2005 and 2012-2015) of Chinese patients using magnetic resonance vessel wall imaging. METHODS: Symptomatic patients with carotid atherosclerotic plaques who underwent carotid vessel wall magnetic resonance imaging between 2002-2005 and 2012-2015 were retrospectively recruited. Plaque morphology [including mean wall area, wall thickness, and maximum normalized wall index (NWI)] and composition [including calcification, intraplaque hemorrhage, and lipid-rich necrotic core (LRNC)] in symptomatic carotid arteries were evaluated and compared between patients in these two time periods. RESULTS: A total of 258 patients, including 129 patients in the 2002-2005 cohort and 129 patients in the 2012-2015 cohort, were recruited. Statin use (49.6%vs. 32.6%, P = 0.004) and hypertension (76.0% vs. 62.8%, P = 0.015) were significantly more common in the 2012-2015 cohort than in the 2002-2005 cohort. Patients in the 2012-2015 cohort also exhibited significantly low plaque burden parameters (allP < 0.05), as well as a lower prevalence (68.2% vs. 89.9%, P < 0.001) and volume percentages of LRNC (11.2% ± 14.2% vs. 25.7% ± 17.7%, P < 0.001). These differences remained significant after adjustment for clinical factors. The differences in the volume percentages of LRNC also remained significant after an additional adjustment for maximum NWI ( P < 0.001). CONCLUSIONS: Patients in the 2012-2015 cohort had a lower plaque burden and volume percentages of LRNC in symptomatic carotid arteries than those in the 2002-2005 cohort. These findings indicate that carotid plaques in the recent cohort had a lower severity and vulnerability.

Deep learning-enhanced T1 mapping with spatial-temporal and physical constraint.

PURPOSE: To propose a reconstruction framework to generate accurate T1 maps for a fast MR T1 mapping sequence. METHODS: A deep learning-enhanced T1 mapping method with spatial-temporal and physical constraint (DAINTY) was proposed. This method explicitly imposed low-rank and sparsity constraints on the multiframe T1 -weighted images to exploit the spatial-temporal correlation. A deep neural network was used to efficiently perform T1 mapping as well as denoise and reduce undersampling artifacts. Additionally, the physical constraint was used to build a bridge between low-rank and sparsity constraint and deep learning prior, so the benefits of constrained reconstruction and deep learning can be both available. The DAINTY method was trained on simulated brain data sets, but tested on real acquired phantom, 6 healthy volunteers, and 7 atherosclerosis patients, compared with the narrow-band k-space-weighted image contrast filter conjugate-gradient SENSE (NK-CS) method, kt-sparse-SENSE (kt-SS) method, and low-rank plus sparsity (L+S) method with least-squares T1 fitting and direct deep learning mapping. RESULTS: The DAINTY method can generate more accurate T1 maps and higher-quality T1 -weighted images compared with other methods. For atherosclerosis patients, the intraplaque hemorrhage can be successfully detected. The computation speed of DAINTY was 10 times faster than traditional methods. Meanwhile, DAINTY can reconstruct images with comparable quality using only 50% of k-space data. CONCLUSION: The proposed method can provide accurate T1 maps and good-quality T1 -weighted images with high efficiency.

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.