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Objective: To investigate whether hemodynamic features of symptomatic intracranial atherosclerotic stenosis (sICAS) might correlate with the risk of stroke relapse, using a computational fluid dynamics (CFD) model., Methods: In a cohort study, we recruited patients with acute ischemic stroke attributed to 50 to 99% ICAS confirmed by computed tomographic angiography (CTA). With CTA-based CFD models, translesional pressure ratio (PR = pressure poststenotic /pressure prestenotic ) and translesional wall shear stress ratio (WSSR = WSS stenotic - throat /WSS prestenotic ) were obtained in each sICAS lesion. Translesional PR ≤ median was defined as low PR and WSSR ≥4th quartile as high WSSR. All patients received standard medical treatment. The primary outcome was recurrent ischemic stroke in the same territory (SIT) within 1 year., Results: Overall, 245 patients (median age = 61 years, 63.7% males) were analyzed. Median translesional PR was 0.94 (interquartile range [IQR] = 0.87-0.97); median translesional WSSR was 13.3 (IQR = 7.0-26.7). SIT occurred in 20 (8.2%) patients, mostly with multiple infarcts in the border zone and/or cortical regions. In multivariate Cox regression, low PR (adjusted hazard ratio [HR] = 3.16, p = 0.026) and high WSSR (adjusted HR = 3.05, p = 0.014) were independently associated with SIT. Patients with both low PR and high WSSR had significantly higher risk of SIT than those with normal PR and WSSR (risk = 17.5% vs 3.0%, adjusted HR = 7.52, p = 0.004)., Interpretation: This work represents a step forward in utilizing computational flow simulation techniques in studying intracranial atherosclerotic disease. It reveals a hemodynamic pattern of sICAS that is more prone to stroke relapse, and supports hypoperfusion and artery-to-artery embolism as common mechanisms of ischemic stroke in such patients. Ann Neurol 2019;85:752-764., (© 2019 American Neurological Association.)

Purpose: Intracranial artery calcification (IAC) has been demonstrated to be correlated with ischemic stroke, cognitive decline, and other vascular events by accumulating evidences from both Western and Asian populations. The proposed study aimed to investigate its potential mechanisms by evaluating the blood flow velocity and pulsatility index (PI) of cerebral arteries., Methods: Consecutive ischemic stroke patients admitted to the Prince of Wales Hospital were recruited after excluding those with atrial fibrillation or poor temporal window. Quantitative measurements of IAC severity were assessed on brain CT scans. Transcranial Doppler (TCD) ultrasonography was performed to evaluate the blood flow velocity of the middle cerebral artery (MCA) and vertebral-basilar artery (VBA)., Results: In total, 318 patients were analyzed. Spearman's correlation analysis demonstrated both high MCA systolic flow velocity and high MCA PI were correlated with IAC Agatston score, p < 0.001 individually. Similar correlation was also found between IAC Agatston score and high VBA velocity/high VBA PI, p ≤ 0.001 individually. Multiple logistic regression analysis showed IAC Agatston score was an independent risk factor for high MCA velocity (OR 1.533; 95% CI 1.235-1.903), high VBA velocity (OR 1.964; 95% CI 1.381-2.794), and high VBA PI (OR 1.200; 95% CI 1.016-1.418), respectively., Conclusion: Heavier IAC might cause generalized artery flow velocity changes and increased pulsatility index, which may indicate high resistance within cerebrovasculature.

Objective: Success in clinical trials of intracranial atherosclerosis (ICAS) is related to accurate identification of high-risk patients. Noninvasive computational fluid dynamics (CFD) of stenotic lesions may enhance therapeutic decision-making. We determined whether physiologic parameters change downstream cerebral hemodynamics in patients with ICAS., Methods: Consecutive ICAS patients who underwent both CT angiography (CTA) and digital subtraction angiography were enrolled. CFD models were made using CTA source images. Inlet boundary conditions were defined using three ranges of systolic blood pressure (BP) (109.2, 158, and 225 mmHg) and hematocrit (27.3, 40.2, and 48.8). Ratios of pressure, shear strain rates (SSR), and flow velocity across the lesion were calculated using CFD simulations. A linear mixed model was used for the statistical analysis of repeated simulations., Results: Among the 56 patients, 32 had moderate stenosis (50-69%) and 24 had severe stenosis (70-99%). A linear mixed model revealed that the ratio of pressure was predicted by systolic BP and stenosis group interaction (P = .036). These pressure decreases were associated with systolic BP (P < .001) and stenosis group (P < .001), but not with hematocrit (P = .337). Post-hoc analysis revealed that pressure decreases were more profound in the severe stenosis than the moderate stenosis group when comparing high and low systolic BP (P = .0108). Ratios of SSR and velocity were only associated in the stenosis group., Conclusions: Our study showed that systolic BP along with the degree of stenosis was associated with pressure decreases across stenotic lesions. Physiologic conditions may superimpose further changes in post-stenotic or downstream blood flow., (Copyright © 2015 by the American Society of Neuroimaging.)

Stroke patients with carotid disease have a high risk of recurrence of disease. By measuring cerebral blood flow volume (BFV) using extracranial duplex technique for clinical estimation of intracranial collaterals, we aimed to investigate the relationship between the presence of intracranial collaterals and stroke recurrence in stroke patients with carotid disease. Consecutive stroke patients indicated for carotid duplex ultrasound investigations in our hospital were recruited during three years' period. Carotid stenosis was diagnosed as ≥50% stenosis and extracranial arterial BFV was measured by using color velocity imaging quantification ultrasound (CVIQ) software. Presence of intracranial collateral flow was defined as a blood flow volume of either ≥370 mL/min in common carotid artery or ≥120 mL/min in vertebral artery. Univariate and multivariate analyses were performed to determine the independent predictors of recurrent stroke. One hundred and twelve stroke patients (19.1%) with ≤50% carotid stenosis were recruited from consecutive ischemic stroke patients. During a mean follow-up of 28.6±13.1 months, recurrent stroke was recorded in 32 (28.6%) out of the total recruited patients. Estimated by blood flow volume measured by CVIQ, the patients with intracranial collateral flow had a lower rate of recurrent stroke than those without (9.5% vs. 33%, P=0.032). After adjusting for potential confounders, the presence of CVIQ-estimated intracranial collateral flow was an independent protector of recurrent stroke (OR, 0.169; 95% CI, 0.034- 0.842; P=0.03). It could be concluded that blood supply through intracranial collateral flow estimated by CVIQ technique may protect stroke patients with carotid stenosis from suffering recurrent stroke.

Background: Intracranial arterial stenosis (ICAS) is the predominant cause of ischemic stroke and transient ischemic attack in Asia. Change of signal intensities (SI) across an ICAS on magnetic resonance angiography (MRA) may reflect its hemodynamic severity., Methods: In-patients with a symptomatic single ICAS detected on 3D time-of-flight MRA were recruited from 2 hospitals. Baseline and 1-year follow-up data were collected. Signal intensity ratio (SIR) [ =  (mean post-stenotic SI -mean background SI)/(mean pre-stenotic SI - mean background SI)] was evaluated on baseline MRA to represent change of SIs across an ICAS. Acute infarct volume was measured on baseline diffusion-weighted images (DWI). Relationships between SIR and baseline characteristics as well as 1y outcomes were evaluated., Results: Thirty-six subjects (86.1% males, mean age 55.0) were recruited. Overall, mean SIR was 0.84±0.23. Mean SIRs were not significantly different between the 23 (63.9%) anatomically severe stenoses and the 13 (36.1%) anatomically moderate stenoses (0.80±0.23 versus 0.92±0.21, p = 0.126). SIR was significantly, linearly and negatively correlated to acute infarct volume on DWI (Spearman correlation coefficient -0.471, p = 0.011). Two patients (5.6%) had recurrent ischemic strokes at 1y, not related to SIR values., Conclusions: Change of signal intensities across an ICAS on MRA may reflect its hemodynamic and functional severity. Future studies are warranted to further verify the relationships between this index and prognosis of patients with symptomatic ICAS.

Background: Changes of signal intensities (SIs) across intracranial atherosclerosis (ICAS) on magnetic resonance angiography (MRA) may reflect hemodynamic impact of the lesion. We evaluated the interobserver reproducibility of an index termed signal intensity ratio (SIR), developed in a previous study to represent the changes of SIs across ICAS on MRA., Methods: Symptomatic ICAS on MRA were retrospectively recruited. Two observers respectively evaluated the images and calculated the SIR as follows, blinded to each other's readings: SIR=(mean poststenotic SI-mean background SI)/(mean prestenotic SI-mean background SI). Statistical analyses were performed to evaluate the interobserver reproducibility of this index., Results: A total of 102 symptomatic ICASs were enrolled, with 36 (35.3%) lesions of 50%-69% MRA stenoses and others being 70%-99% stenoses or flow void on MRA. Overall, mean SIRs were not significantly different between the 2 observers (.92±.17 versus .93±.17; mean difference -.006±.09; P=.496 for paired t test). Pearson correlation coefficients were >.80 for all analyses, indicating strong linear correlations between SIRs by the 2 observers. Bland-Altman analysis for SIRs of all cases showed no systematic bias between the 2 observers. For different cut-points ranging from .75 to 1.00, the kappa statistics were mostly greater than .6 and interobserver agreements were all greater than 80%, implying substantial agreement between observers., Conclusions: SIR was demonstrated to be highly reproducible between observers in the present study. Future studies are warranted to further explore the role of this index in comprehensive evaluation and risk stratification of symptomatic ICAS., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

BackgroundPatients with symptomatic intracranial atherosclerosis (ICAS) of ≥ 70% luminal stenosis are at high risk of stroke recurrence. We aimed to evaluate the relationships between hemodynamics of ICAS revealed by computational fluid dynamics (CFD) models and risk of stroke recurrence in this patient subset.MethodsPatients with a symptomatic ICAS lesion of 70-99% luminal stenosis were screened and enrolled in this study. CFD models were reconstructed based on baseline computed tomographic angiography (CTA) source images, to reveal hemodynamics of the qualifying symptomatic ICAS lesions. Change of pressures across a lesion was represented by the ratio of post- and pre-stenotic pressures. Change of shear strain rates (SSR) across a lesion was represented by the ratio of SSRs at the stenotic throat and proximal normal vessel segment, similar for the change of flow velocities. Patients were followed up for 1 year.ResultsOverall, 32 patients (median age 65; 59.4% males) were recruited. The median pressure, SSR and velocity ratios for the ICAS lesions were 0.40 (-2.46-0.79), 4.5 (2.2-20.6), and 7.4 (5.2-12.5), respectively. SSR ratio (hazard ratio [HR] 1.027; 95% confidence interval [CI], 1.004-1.051; P = 0.023) and velocity ratio (HR 1.029; 95% CI, 1.002-1.056; P = 0.035) were significantly related to recurrent territorial ischemic stroke within 1 year by univariate Cox regression, respectively with the c-statistics of 0.776 (95% CI, 0.594-0.903; P = 0.014) and 0.776 (95% CI, 0.594-0.903; P = 0.002) in receiver operating characteristic analysis.ConclusionsHemodynamics of ICAS on CFD models reconstructed from routinely obtained CTA images may predict subsequent stroke recurrence in patients with a symptomatic ICAS lesion of 70-99% luminal stenosis.

Background: Collateral pathways are important in maintaining adequate cerebral blood flow in patients with carotid stenosis. We aimed to evaluate the hemodynamic patterns in relation to carotid stenosis in acute stroke patients.Methods: Consecutive 586 stroke patients in a hospital based cohort were included in the present study. Carotid duplex was performed to identify patients with absolute minimal diameter reductions of 50% or greater in their internal carotid arteries (ICAs). Color velocity imaging quantification ultrasound (CVIQ) was used to measure extracranial arterial blood flow volume (BFV) in bilateral common carotid arteries (CCAs) and bilateral vertebral arteries (VAs). The absolute values of BFV and the ratios were compared between patients with and without ICA stenosis.Results: Among 586 acute ischemic stroke patients (mean age: 67.5 ± 12.4y), ICA stenosis was detected in 112 patients (19.1%), including unilateral ICA stenosis in 81 patients (13.8%) and bilateral ICA stenosis in 31 patients (5.3%). Among patients with unilateral ICA stenosis, the BFV in contralateral CCA was significantly higher than that in ipsilateral CCA (325.5 ± 99.8 mL/min vs. 242.2 ± 112.2 mL/min, P < 0.001). Among patients with bilateral ICA stenosis, the sum of BFV in bilateral VAs accounted for 22% of the whole cerebral blood flow, which was significantly higher than that in those without ICA stenosis (14.8%, P < 0.001) or with unilateral ICA stenosis (16.9%, P = 0.007).Conclusions: In patients with unilateral carotid stenosis, contralateral carotid blood flow increases to compensate decreased blood flow, while posterior circulation may compensate for the decreased brain perfusion in those with bilateral carotid stenosis. [ABSTRACT FROM AUTHOR]

Background and Purpose: Increased cerebral blood flow velocity of basilar artery (BA) is common but often neglected. By using digital subtraction angiography (DSA) to detect intracranial large artery stenosis, we performed transcranial Doppler (TCD) to evaluate cerebral hemodynamic changes of stroke patients. Methods: Acute stroke patients with TCD-detected raised peak systolic velocity (PSV) in BA (≥100 cm/second) were recruited. Results: Among 91 recruited patients, BA stenosis (>50%) was confirmed by using DSA in 29 patients (32%), among which 20 patients (70.0%) had coexistent internal carotid artery (ICA) and vertebral artery (VA) stenoses. Among patients without BA stenosis (n = 62, 68%), severe stenosis or occlusion of ICA was evaluated in 22 patients (22/62, 35.4%) and severe stenosis or occlusion of VA was detected in 22 patients (22/62, 35.4%). Among the values of PSV (120, 140, 160, and 180 cm/second) and the stenotic-to-prestenotic ratio (SPR) (1.5, 2.0, 2.5, and 3.0), 160 cm/second was found to show the highest predictive value (area under the receiver operator characteristic curve: .75, 95% CI: .65-.86), with a sensitivity of .70 and a specificity of .81. Conclusions: Apart from an intrinsic BA stenosis, high-grade steno-occlusion of ICA or VA may contribute a lot to induce an elevated flow velocity in BA. A higher value of cutoff point may increase the accuracy of diagnosing BA stenosis. [ABSTRACT FROM AUTHOR]

Abstract: External counterpulsation (ECP) is a noninvasive method used to augment cerebral perfusion but the optimal use of ECP in ischemic stroke has not been well documented. We aimed to investigate the effects of ECP treatment pressure on cerebral blood flow and blood pressure (BP). We recruited 38 ischemic stroke patients with large artery occlusive disease and 20 elderly controls. We commenced ECP treatment pressure at 150mmHg and gradually increased to 187.5, 225 and 262.5mmHg. Mean cerebral blood flow velocities (CBFV) of bilateral middle cerebral arteries and continuous beat-to-beat BP were recorded before ECP and during each pressure increment for 3minutes. Patient CBFV data was analyzed based on whether it was ipsilateral or contralateral to the infarct. Mean BP significantly increased from baseline in both stroke and control groups after ECP commenced. BP increased in both groups following raised ECP pressure and reached maximum at 262.5mmHg (patients 16.9% increase versus controls 16.52%). The ipsilateral CBFV of patients increased 5.15%, 4.35%, 4.55% and 3.52% from baseline under the four pressures, respectively. All were significantly higher than baseline but did not differ among different ECP pressures; contralateral CBFV changed likewise. Control CBFV did not increase under variable pressures of ECP. ECP did increase CBFV of our patients to a roughly equal degree regardless of ECP pressure. Among the four ECP pressures tested, we recommend 150mmHg as the optimal treatment pressure for ischemic stroke due to higher risks of hypertension-related complications with higher pressures. [Copyright &y& Elsevier]

Objective: To identify determinants associated with increasing severity of middle cerebral artery (MCA) stenosis in asymptomatic Chinese type 2 diabetic patients with and without MCA stenosis determined using transcranial Doppler. Conventional risk factors contribute to the pathogenesis of ischemic stroke, and differences in the pattern of these may explain the heterogeneity of disease presentation in different populations. In Chinese patients, MCA stenosis is the most commonly identified intracranial vascular lesion.Research Design and Methods: Anthropometric and fasting biochemical parameters were compared between type 2 diabetic patients with MCA stenosis in one (n = 185) or both (n = 200) vessels and 1,492 type 2 diabetic patients without evidence of stenosis.Results: Increasing MCA stenotic vascular involvement was associated with significantly increasing age, duration of diabetes, systolic blood pressure, and LDL cholesterol, but with lower glucose levels. There was also an increased prevalence of hypertension, dyslipidemia, and use of blood pressure-and glucose-lowering agents in the patients with MCA stenosis. Concomitant significant increases in the prevalence of peripheral vascular disease and retinopathy were also observed in the patients with MCA stenosis.Conclusions: Transcranial Doppler examination identified stenosis in one or both MCAs in over one-fifth of the Chinese type 2 diabetic subjects without symptoms of cerebrovascular disease. A number of conventional cardiovascular risk factors were closely associated with MCA stenosis. This technique may allow the identification of a particularly high-risk group, and further studies are required to determine whether asymptomatic MCA stenosis is predictive of primary cerebrovascular events and whether intensive treatment of risk factors would reduce the risk. [ABSTRACT FROM AUTHOR]