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Objective: Whether the cerebral vascular variations play an important role in the progression of intracranial atherosclerosis is yet largely unclear. We aimed to investigate the relationship between the magnitude of the vertebrobasilar junction (VBJ) angle and the imaging features of vertebrobasilar artery atherosclerosis.Methods: Adult patients with acute ischemic stroke or transient ischemic attack undergoing a 3.0-tesla vessel wall magnetic resonance imaging (VW-MRI) scanning were consecutively included. Imaging features of vertebrobasilar artery atherosclerosis were assessed on the reconstructed short axis of VW-MRI at the most stenotic site. The VBJ angle degree was measured on magnetic resonance angiography and classified into the angle ≥90° or

Background and Purpose: Intracranial arterial calcification (IAC) has been the focus of much attention by clinicians and researchers as an indicator of intracranial atherosclerosis, but correlations of IAC patterns (intimal or medial) with the presence of atherosclerotic plaques and plaque stability are still a matter of debate. Our study aimed to assess the associations of IAC patterns identified on computed tomography (CT) with the presence of plaque detected on vessel wall magnetic resonance imaging and plaque stability.Materials and Methods: Patients with stroke or transient ischemic attack and intracranial artery stenosis were recruited. IAC was detected and localized (intima or media) on non-contrast CT images. Intracranial atherosclerotic plaques were identified using vessel wall magnetic resonance imaging and matched to corresponding CT images. Associations between IAC patterns and culprit atherosclerotic plaques were assessed by using multivariate regression.Results: Seventy-five patients (mean age, 63.4 ± 11.6 years; males, 46) were included. Two hundred and twenty-one segments with IAC were identified on CT in 66 patients, including 86 (38.9%) predominantly intimal calcifications and 135 (61.1%) predominantly medial calcifications. A total of 72.0% of intimal calcifications coexisted with atherosclerotic plaques, whereas only 10.2% of medial calcifications coexisted with plaques. Intimal calcification was more commonly shown in non-culprit plaques than culprit plaques (25.9 vs. 9.4%, P = 0.008). The multivariate mixed logistic regression adjusted for the degree of stenosis showed that intimal calcification was significantly associated with non-culprit plaques (OR, 2.971; 95% CI, 1.036–8.517; P = 0.043).Conclusion: Our findings suggest that intimal calcification may indicate the existence of a stable form of atherosclerotic plaque, but plaques can exist in the absence of intimal calcification especially in the middle cerebral artery.

Objective: Investigating the relevance of the incomplete circle of Willis (COW) to the plaque wall distribution in the atherosclerotic middle cerebral arteries (MCAs) through utilizing high-resolution magnetic resonance imaging (HR-MRI), and its potential clinical impact.Methods: This hospital-based study enrolled consecutive adult patients with acute ischemic stroke or transient ischemic attack, who received a 3.0T Achieva MR system scanning. The COW completeness was evaluated on MR angiography imaging, including anterior (A) and posterior (P)-COW sections. The MCA plaque wall distribution was assessed on HR-MRI. The occurrence of perforator infarction was detected on diffusion-weighted imaging.Results: Among 87 patients (mean age = 62.39 ± 11.64 years old) with atherosclerotic plaques in the MCA M1 segments, the incomplete COW types were more prevalent than the complete COW type (incomplete P-COW, 83.9%; incomplete A-COW, 36.8%; complete COW, 8.1%). The incomplete A-COW had more inferior but fewer ventral plaques of MCA atherosclerosis than the complete A-COW, while the incomplete P-COW had fewer inferior MCA plaques than the complete P-COW. Moreover, symptomatic MCA plaques causing perforator infarctions were more likely to locate on the superior wall.Conclusion: Our findings suggested that the COW completeness could influence the vessel wall distribution of the MCA plaques, among which the superior plaques of symptomatic MCA atherosclerosis was associated with branch occlusive disease.

Background: Intracranial arterial calcification (IAC) is highly prevalent in ischemic stroke patients. However, data on the association of IAC with stroke recurrence and mortality remains limited. We examined the effect of IAC on the long-term recurrence of stroke and the risk of post-stroke mortality.Methods: Using a prospective stroke registry, we recruited 694 patients (mean age 71.6 ± 12.4; male sex 50.3%) since December 2004. IAC was visualized using the computed tomography exam that was made at hospital admission and was quantified with the Agatston method. All patients were regularly followed up till July 2016. The impacts of IAC on stroke recurrence and mortality were assessed using Cox-regression models with adjustments for age, sex, and relevant cardiovascular risk factors.Results: During a median follow-up period of 8.8 years, 156 patients (22.5%) suffered a recurrent stroke and 84 died (12.1%). We found that a higher IAC Agatston score related to a higher risk of stroke recurrence (HR per 1-SD increase in IAC: 1.30; 95% CI, 1.08–1.56, p = 0.005) and a higher risk of post-stroke mortality (HR per 1-SD increase, 1.44; 95% CI, 1.06–1.96, p = 0.019). After investigating etiology-specific risks of stroke-recurrence, we found that a higher IAC Agatston score specifically associated with small-vessel occlusive stroke.Conclusions: IAC is a strong risk factor for recurrent stroke and post-stroke mortality. Among stroke subtypes, IAC relates to higher risk of stroke recurrence among patients with small-vessel disease, which indicates chronic calcification detected in large cerebral arteries may have potential effects on the cerebrovascular beds extending to small vessels.

Objective: Contrast enhancement is a vital feature of the intracranial atherosclerotic plaque on high-resolution magnetic resonance imaging (HRMRI), but its clinical significance is still unclear. We aimed to quantitatively assess plaque enhancement patterns in the middle cerebral artery (MCA) atherosclerotic plaque.Methods: We conducted a cross-sectional study by prospectively recruiting stroke or transient ischemic attack patients with >30% of MCA stenosis of either side. All patients underwent contrast-enhanced HRMRI scans. Enrolled patients were classified into acute phase (12 weeks) groups based on the time interval from stroke onset to imaging scan. Plaque enhancement index was calculated for each MCA lesion at the maximal narrowing site.Results: We identified a total of 89 MCA plaques [53 (60%) symptomatic and 36 (40%) asymptomatic; 57 (64%) acute, 18 (20%) subacute and 14 (16%) chronic] in 58 patients on HRMRI. Among the acute lesions, symptomatic plaques had a significantly stronger plaque enhancement than asymptomatic plaques (symptomatic vs. asymptomatic: 38.9 ± 18.2 vs. 18.2 ± 16.2, p < 0.001). Among the symptomatic lesions, plaque enhancement diminished with increasing time after stroke onset (38.9 ± 18.2, 22.0 ± 22.8, and 5.0 ± 10.1 for acute, subacute, and chronic phase, respectively; p = 0.001).Conclusion: Plaque enhancement in the acute atherosclerotic plaque is closely related to recent ischemic events. In symptomatic atherosclerosis, plaque enhancement regresses over time after ischemic stroke, which may offer the potential to monitor the plaque activity in intracranial atherosclerosis using HRMRI.

BackgroundPost-stroke behavioral disinhibition (PSBD) is common in stroke survivors and often presents as impulsive, tactless or vulgar behavior. However, it often remains undiagnosed and thus untreated, even though it can lead to a longer length of stay in a rehabilitation facility. The proposed study will aim to evaluate the clinical, neuropsychological and magnetic resonance imaging (MRI) correlates of PSBD in a cohort of stroke survivors and describe its 12-month course.MethodsThis prospective cohort study will recruit 237 patients and will be conducted at the Neurology Unit of the Prince of Wales Hospital. The project duration will be 24 months. The patients will be examined by multiple MRI methods, including diffusion-weighted imaging, within 1 week after stroke onset. The patients and their caregivers will receive a detailed assessment at a research clinic at 3, 9 and 15 months after stroke onset (T1, T2 and T3, respectively). The disinhibition subscale of the Frontal Systems Behavior Scale (FrSBe) will be completed by each subject and caregiver, and scores ≥65 will be considered to indicate PSBD.A stepwise logistic regression will be performed to assess the importance of lesions in the regions of interest (ROIs), together with other significant variables identified in the univariate analyses. For patients with PSBD at T1, the FrSBe disinhibition scores will be compared between the groups of patients with and without ROI infarcts, using covariance analysis. The demographic, clinical and MRI variables of remitters and non-remitters will be examined again at T2 and T3 by logistic regression.DiscussionThis project will be the first MRI study on PSBD in stroke survivors. The results will shed light on the associations of lesions in the orbitofrontal cortex, anterior temporal lobe and subcortical brain structures with the risk of PSBD. The obtained data will advance our understanding of the pathogenesis and clinical course of PSBD in stroke, as well as other neurological conditions. The findings are thus likely to be applicable to the large population of patients with neurological disorders at risk of PSBD and are expected to stimulate further research in this field.

RationalePost-stroke fatigue (PSF) is a frequent problem in stroke survivors and often hinders their rehabilitation. PSF is difficult to treat, and pharmacological therapy is often ineffective. Transcranial direct current stimulation (tDCS) can modulate motor, sensory, cognitive and behavioral responses, as it alters neuronal activity by delivering a small amount of current via the scalp to the cortex, resulting in prolonged alterations to brain function. tDCS has been studied for the treatment of fatigue associated with other neurological diseases, namely, multiple sclerosis, Parkinson’s disease and post-polio syndrome.AimsThis proposed project will examine the effect of tDCS on PSF.Sample size estimatesWe will recruit 156 participants aged 18 to 80 with chronic stroke and allocate them equally to two groups (i.e., n = 78 per group).Methods and designThis proposed project will be a double-blind randomized control trial. The participants will be randomly divided into two groups. The control group will receive sham tDCS, and the treatment group will receive active tDCS. The latter treatment will involve application of a constant 2-mA current via one 5 × 5-cm anodal electrode positioned on the scalp over the C3 or C4 positions (motor cortex) of the lesioned hemisphere and one cathodal electrode positioned at the ipsilateral shoulder in two 20-min sessions per day for 5 days. The period of follow-up will be 4 weeks.Study outcome(s)The primary outcome measure will be a change in fatigue severity, as measured using the modified fatigue impact scale (MFIS). The participants’ scores on the MFIS (total score and physical, cognitive and psychosocial subscores) will be collected before treatment (T0), after 10 treatment sessions, i.e., 1 day after the fifth treatment day (T1), and 1 week (T2), 2 weeks (T3) and 4 weeks (T4) thereafter. Both per-protocol analysis and intention-to-treat analysis will be performed.DiscussionThis proposed project will provide proof-of-concept, i.e., demonstrate the benefits of tDCS for the treatment of PSF. The beneficiaries are the subjects participated in the study. This will stimulate further research to optimize tDCS parameters for the treatment of PSF.Clinical trial registrationwww.Chictr.org.cn, identifier: ChiCTR2100052515.

BackgroundPoststroke irritability (PSI) is common among stroke survivors and can lead to a poor quality of life, difficulties in social interactions, criticism from caregivers, and caregiver stress. The planned study will evaluate the clinical, neuropsychological, and magnetic resonance imaging (MRI) correlates of PSI in a cohort of stroke survivors. In addition, the study will examine the 15-month progression of PSI.MethodsThis will be a prospective cohort study that will recruit 285 participants. Participants and their caregivers will undergo detailed assessments at a research clinic at 3, 9, and 15 months after stroke onset (T1/T2/T3). The irritability/lability subscale of the Chinese version of the Neuropsychiatric Inventory (CNPI) will be completed by caregivers. Potential covariates will also be measured. Patients will undergo MRI, including diffusion-weighted imaging, within 1 week of stroke onset. A stepwise logistic regression will be performed to evaluate the importance of lesions in the regions of interest (ROIs) along with other significant variables identified in univariate analyses. These analyses will be repeated for patients with and without PSI at T2 and T3. Repeated measures analysis of covariance (ANCOVA) will be used to assess changes in CNPI scores for the entire sample. In ANCOVA analyses, the frequency of infarcts in the ROIs will be treated as the predictor.DiscussionThis will be the first MRI study on PSI in stroke survivors. The findings will provide insights into the association of the orbitofrontal cortex, anterior cingulate cortex, anterior temporal lobe, insula, amygdala, thalamus, and basal ganglia lesions with the risk of PSI.

BackgroundLoss of empathy (LoE) is common among stroke survivors, yet often undiagnosed and thus untreated. LoE is related to the loss of a caring marital relationship, higher care burden and poorer quality of life in carers. The present study will evaluate the clinical and MRI correlates of LoE in a cohort of stroke survivors. The secondary objective is to describe the 12-month course of LoE.MethodsThe current study is a prospective cohort study. We will recruit 246 subjects. Subjects and carers will receive a detailed assessment at a research clinic at 3, 9, and 15 months after stroke onset (T1/T2/T3). The Chinese version of the Interpersonal Reactivity Index (IRI), a 28-item personality assessment tool, will be completed by a carer for each subject. LoE is defined as an IRI total score of 39 or less. Patients will be examined by MRI including diffusion weighted imaging (DWI) within 1 week after the onset of stroke. A stepwise logistic regression will be performed to assess the importance of lesions in the regions of interest. To examine the predictors of LoE remission, the demographic, clinical and MRI variables of remitters and non-remitters at T2/T3 will be examined by logistic regression.DiscussionThis project will be the first longitudinal study on LoE in stroke survivors. The results will shed light on the association between prefrontal cortex and subcortical lesions and LoE risk, symptom severity and outcome. The findings will provide data to advance our understanding of the pathogenesis and clinical course of LoE in stroke as well as other neurological conditions. They are thus likely to be applicable to the large population of neurological patients at risk of LoE and should also stimulate further research in this field.

Background: Various computational models of the circle of Willis (CoW) have been developed to non-invasively estimate the blood flow and hemodynamic parameters in intracranial arteries for the assessment of clinical risks such as aneurysms, ischemia, and atherosclerotic plaque growth. This review aims to categorize the latest computational models of CoW and summarize the innovative techniques. Summary of Review: In traditional computational models of CoW, the computational complexity increased from zero-dimensional models to one-dimensional and three-dimensional models. The applications extend from estimating certain hemodynamic parameters to simulating local flow field. The innovative techniques include the combination of models with different dimensions, the extension of vascular structure including heart and veins, as well as the addition of distal fractality, cerebral autoregulation, and intracranial pressure. There are some nontraditional models based on fluid-solid-interaction, control theory, and in-vitro experiments. In all kinds of models, the in-vivo data and non-Newtonian rheological models of blood have been widely applied to improve the accuracy of hemodynamic simulation. Conclusion: Firstly, the selection of model depends on its application scenario. The balance between computational complexity and physiological accuracy deserves further investigation. Secondly, the improvement of CoW models relies on the large-scale validations and the combination of various innovative modeling techniques.

Instantaneous wave-free ratio (iFR) has been proposed as a hemodynamic parameter that can reliably reflect the blood flow in stenosed coronary arteries. Currently, there are few investigations on the quantitative analysis of iFR in the patients regarding the variation of microcirculatory resistance (MR). The data aim to provide geometric (cross-section area of branches) and hemodynamic (flow rate and iFR of branches) parameters of normal and stenosed coronary arteries derived from CFD simulation. The CFD simulation was performed on the three-dimensional artery models reconstructed from computed tomography (CT) images of four subjects. The hemodynamic parameters were obtained in six situations of MR to simulate coronary microvascular dysfunction (CMD). This dataset could be used as the reference to estimate the iFR and flow rate in patients with CMD and stenosis in coronary arteries. The geometric parameters could be used in the modelling of coronary arteries.

Background and Purpose Vasa vasorum (VV) have been believed to be rare or non-existent in small-caliber intracranial arteries. In a series of human cerebral artery specimens, we identified and examined the distribution of VV in association with co-existing intracranial atherosclerosis. Methods We obtained cerebral artery specimens from 32 consecutive autopsies of subjects aged 45 years or above. We scrutinized middle cerebral artery (MCA), vertebral artery (VA), and basilar artery (BA) for the presence of adventitial VV. We described the distribution of VV, and the characteristics of co-existing atherosclerotic lesions. Results Among 157 intracranial arteries, adventitial VV were present in 74 of the 157 specimens (47%), involving MCA (n=13, 18%), BA (n=14, 19%), and VA (n=47, 64%). Although qualitatively these 74 adventitial VV distributed similarly in arteries with or without atherosclerotic lesions (disease-free arteries n=4/8; arteries of pre-atherosclerosis n=17/42; and arteries of progressive atherosclerosis n=53/107), the presence of adventitial VV in intracranial VA was associated with a heavier plaque load (1.72±1.66 mm2 vs. 0.40±0.32 mm2, P