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We aimed to investigate the roles of antegrade residual flow and leptomeningeal collateral flow in sustaining cerebral perfusion distal to an intracranial atherosclerotic stenosis (ICAS). Patients with apparently normal cerebral perfusion distal to a symptomatic middle cerebral artery (MCA)-M1 stenosis were enrolled. Computational fluid dynamics models were built based on CT angiography to obtain a translesional pressure ratio (PR) to gauge the residual antegrade flow. Leptomeningeal collaterals (LMCs) were scaled on CT angiography. Cerebral perfusion metrics were obtained in CT perfusion maps. Among 83 patients, linear regression analyses revealed that both translesional PR and LMC scale were independently associated with relative ipsilesional mean transit time (rMTT). Subgroup analyses showed that ipsilesional rMTT was significantly associated with translesional PR ( p  < 0.001) rather than LMC scale in those with a moderate (50-69%) MCA stenosis, which, however, was only significantly associated with LMC scale ( p  = 0.051) in those with a severe (70-99%) stenosis. Antegrade residual flow and leptomeningeal collateral flow have complementary effects in sustaining cerebral perfusion distal to an ICAS, while cerebral perfusion may rely more on the collateral circulation in those with a severe stenosis.

Collateral circulation plays a vital role in sustaining blood flow to the ischaemic areas in acute, subacute or chronic phases after an ischaemic stroke or transient ischaemic attack. Good collateral circulation has shown protective effects towards a favourable functional outcome and a lower risk of recurrence in stroke attributed to different aetiologies or undergoing medical or endovascular treatment. Over the past decade, the importance of collateral circulation has attracted more attention and is becoming a hot spot for research. However, the diversity in imaging methods and criteria to evaluate collateral circulation has hindered comparisons of findings from different cohorts and further studies in exploring the clinical relevance of collateral circulation and possible methods to enhance collateral flow. The statement is aimed to update currently available evidence and provide evidence-based recommendations regarding grading methods for collateral circulation, its significance in patients with stroke and methods under investigation to improve collateral flow., Competing Interests: Competing interests: None declared.

Background: Computational fluid dynamics (CFD) allows noninvasive fractional flow (FF) computation in intracranial arterial stenosis. Removal of small artery branches is necessary in CFD simulation. The consequent effects on FF value needs to be judged., Methods: An idealized vascular model was built with 70% focal luminal stenosis. A branch with one third or one half of the radius of the parent vessel was added at a distance of 5, 10, 15 and 20 mm to the lesion. With pressure and flow rate applied as inlet and outlet boundary conditions, CFD simulations were performed. Flow distribution at bifurcations followed Murray's law. By including or removing side branches, five patient-specific intracranial artery models were simulated. Transient simulation was performed on a patient-specific model, with a larger branch for validation. Branching effect was considered trivial if the FF difference between paired models (branches included or removed) was within 5%., Results: Compared with the control model without a branch, in all idealized models the relative differences of FF was within 2%. In five pairs of cerebral arteries (branches included/removed), FFs were 0.876 and 0.877, 0.853 and 0.858, 0.874 and 0.869, 0.865 and 0.858, 0.952 and 0.948. The relative difference in each pair was less than 1%. In transient model, the relative difference of FF was 3.5%., Conclusion: The impact of removing side branches with radius less than 50% of the parent vessel on FF measurement accuracy is negligible in static CFD simulations, and minor in transient CFD simulation., (Copyright © 2018. Published by Elsevier Inc.)

Cerebral autoregulation (CA) is a protective mechanism that maintains cerebral blood flow at a relatively constant level despite fluctuations of cerebral perfusion pressure or arterial blood pressure. It is a universal physiological mechanism that may involve myogenic, neural control as well as metabolic regulations of cerebral vasculature in response to changes in pressure or cerebral blood flow. Traditionally, CA has been represented by a sigmoid curve with a wide plateau between about 50 mm Hg and 170 mm Hg of steady-state changes in mean arterial pressure, defined as static CA. With the advent of transcranial Doppler, measurement of cerebral blood flow in response to transient changes in arterial pressure has been used to assess dynamic CA. However, a gold standard for measuring CA is not currently available. Stroke has been the leading cause of long-term adult disability throughout the world. A better understanding of CA and its response to pathological derangements can help assess the severity of stroke, guide management decisions, assess response to interventions and provide prognostic information. The objective of this review is to provide a comprehensive insight about physiology of autoregulation, measurement methodologies and clinical applications in stroke to help build a consensus for what should be included in an internationally agreed protocol for CA testing and monitoring, and to promote its translation into clinical bedside practice for stroke management., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: Whether dynamic cerebral autoregulation (dCA) is impaired focally in the affected hemisphere or bilaterally in both the affected and nonaffected hemispheres after ischemic stroke remains controversial. We therefore investigated the pattern of dCA in acute ischemic stroke patients with different subtypes., Methods: Sixty acute ischemic stroke patients with unilateral anterior circulation infarct [30 with large artery atherosclerosis (LAA), 13 with small vessel disease (SVD), and 17 with coexisting LAA and SVD] and 16 healthy controls were enrolled. Spontaneous arterial blood pressure and cerebral blood flow velocity fluctuations in both bilateral middle cerebral arteries using transcranial Doppler were recorded over 10 minutes. Transfer function analysis was applied to obtain autoregulatory parameters, autoregulation index (ARI), phase difference (PD), and gain., Results: PD was significantly lower on both the ipsilateral and contralateral sides in the LAA group (ipsilateral, 30.74 degrees; contralateral, 29.17 degrees) and the coexisting LAA and SVD group (20.23 degrees; 13.10 degrees) than that in healthy controls (left side, 51.66 degrees; right side, 58.48 degrees) (all P < .05), but there were no significant differences between the 2 sides when compared with each other in all groups. However, in the coexisting LAA and SVD group, phase on both sides was significantly lower when compared with that in the LAA and SVD groups, respectively. The results of ARI were consistent with the findings in PD., Conclusions: The results indicate that dCA is bilaterally impaired in acute ischemic patients with LAA, and the coexisting SVD may aggravate the bilateral impairment of dCA., (Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Objective: External counterpulsation (ECP) is a non-invasive method used to augment cerebral perfusion in ischaemic stroke. We aimed to investigate time-course effects on blood pressure elevation and cerebral blood flow augmentation induced by ECP in ischaemic stroke., Methods: Patients with acute unilateral ischaemic stroke and large artery occlusive disease were recruited to receive 35 daily 1 h ECP treatment sessions. Serial transcranial Doppler monitoring of bilateral middle cerebral arteries was performed on days 3, 5, 7, 10, 14, 21, 28 and 35 after stroke onset. Flow velocity changes before, during and after ECP and continuous beat-to-beat blood pressure data were recorded. The cerebral augmentation index (CAI) is the increase in the percentage of the middle cerebral artery mean flow velocity during ECP compared with baseline., Results: The CAI in patients with stroke was significantly higher on the ipsilateral side and on the contralateral side on day 3 (ipsilateral CAI, 9.3%; contralateral CAI, 7.2%), day 5 (7.0%; 6.7%), day 7 (6.8%; 6.0%), day 10 (6.0%; 5.1%), day 14 (4.7%; 2.6%) and day 21 (4.1%; 2.2%) after stroke onset than that in controls (-2.0%) (all p<0.05). There was a significant trend of decreasing CAI on the ipsilateral and contralateral sides over time after a stroke. Differences in the percentage increase in the mean blood pressure did not change significantly over time in patients with stroke., Conclusions: Blood pressure elevation persists throughout ECP treatment, which consists of 35 sessions. However, cerebral blood flow augmentation may last at least 3 weeks and then appears to return to baseline 1 month after acute stroke onset., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

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 150 mmHg and gradually increased to 187.5, 225 and 262.5 mmHg. 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 3 minutes. 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 262.5 mmHg (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 150 mmHg as the optimal treatment pressure for ischemic stroke due to higher risks of hypertension-related complications with higher pressures., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

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.)

Background and Purpose: External counterpulsation (ECP) is a novel noninvasive method used to improve the perfusion of vital organs, which may benefit ischemic stroke patients. We hypothesized that ECP may augment cerebral blood flow of ischemic stroke patients via induced hypertension., Methods: We recruited ischemic stroke patients with cerebral intracranial large artery occlusive disease and healthy elderly controls into this study. Bilateral middle cerebral arteries of subjects were monitored using transcranial Doppler. Flow velocity changes before, during, and after ECP were, respectively, recorded for 3 minutes while continuous beat-to-beat blood pressure data were recorded. Cerebral augmentation index was the increase in percentage of middle cerebral artery mean flow velocity during ECP compared with baseline. Transcranial Doppler data were analyzed based on ipsilateral or contralateral to the infarct side., Results: ECP significantly increased mean blood pressure of stroke patients and controls. During ECP, middle cerebral artery mean flow velocities of stroke patients increased on both ipsilateral and contralateral sides when compared with baseline (ipsilateral cerebral augmentation index, 9.64%; contralateral cerebral augmentation index, 9%; both P<0.001), but there was no increase in difference between the 2 sides when compared with each other. Mean flow velocities of controls did not change under ECP. After ECP, blood pressure and flow velocity of stroke patients returned to baseline level., Conclusions: ECP provides a new method of cerebral blood flow augmentation in ischemic stroke by elevation of blood pressure. Flow augmentation induced by ECP suggests the improvement of cerebral perfusion and collateral supply from infarct ipsilateral and contralateral sides.

Background: Collateral circulation stabilizes cerebral blood flow in patients with acute occlusion, but its prognostic role is less studied in intracranial atherosclerosis and appears different in moderate to severe stenosis. We aimed to study the associations between antegrade flow across stenosis, collateral flow via leptomeningeal anastomosis, and the neurological outcome and recurrence risk in patients with symptomatic intracranial stenosis., Methods: We examined a cohort of consecutive patients admitted for stroke or transient ischemic attack (TIA) with symptomatic intracranial stenosis confirmed by digital subtraction angiography in a single-center retrospective study. Angiograms were graded systematically in a blinded fashion for antegrade and collateral flow, using Thrombolysis in Cerebral Infarction (TICI) and American Society of Intervention and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grading, respectively, and integrated to a simple composite circulation score. Demographic and clinical variables, modified Rankin Scale (mRS) scores at 3 months, recurrent stroke or TIA in 12 months were collected. Uni- and multivariate analyses were performed to identify independent predictors of good outcome (mRS 0-2) and recurrence in a logistic regression model., Results: Among 69 patients with pure intracranial atherosclerosis ≥ 50%, compromised antegrade flow (TICI 0-2a) was observed in 26 (36%) patients and was associated with more severe arterial stenosis (mean 86 vs. 74%, p = 0.001). Poor collateral compensation resulting in a poor composite circulation score was observed in 8 (12%) patients. Patients with a good circulation score (n = 61, 88%) had preserved flow, which was associated with more favorable outcome (OR 7.50, 95% CI 1.11-50.7, p = 0.04) and less recurrent TIA or stroke (OR 0.18, 95% CI 0.04-0.96, p = 0.04). Prognosis was not significantly associated with antegrade or collateral grade per se., Conclusion: Good collateral compensations are more important in patients with symptomatic intracranial stenosis and compromised antegrade flow, and are associated with favorable outcome and less recurrence risk. The feasibility of composite flow assessment should be explored in future studies to identify high-risk intracranial stenosis with compromised hemodynamics., (Copyright © 2012 S. Karger AG, Basel.)

Background and Purpose: External counterpulsation (ECP) improves coronary perfusion, increases left ventricular stroke volume similar to intraaortic balloon counterpulsation, and recruits arterial collaterals within ischemic territories. We sought to determine ECPs effect on middle cerebral artery (MCA) blood flow augmentation in normal controls as a first step to support future clinical trials in acute stroke., Methods: Healthy volunteers were recruited and screened for exclusions. Bilateral 2-MHz pulsed wave transcranial Doppler (TCD) probes were mounted by head frame, and baseline M1 MCA TCD measurements were obtained. ECP was then initiated using standard procedures for 30 minutes, and TCD readings were repeated at 5 and 20 minutes. Physiological correlates associated with ECP-TCD waveform morphology were identified, and measurable criteria for TCD assessment of ECP arterial mean flow velocity (MFV) augmentation were constructed., Results: Five subjects were enrolled in the study. Preprocedural M1 MCA TCD measurements were within normal limits. Onset of ECP counterpulsation produced an immediate change in TCD waveform configuration with the appearance of a second upstroke at the dicrotic notch, labeled peak diastolic augmented velocity (PDAV). Although end-diastolic velocities did not increase, both R-MCA and L-MCA PDAVs were significantly higher than baseline end-diastolic values (P<0.05 Wilcoxon rank-sum test) at 5 and 20 minutes. Augmented MFVs (aMFVs) were also significantly higher than baseline MFV in the R-MCA and L-MCA at both 5 and 20 minutes (P<0.05)., Conclusions: ECP induces marked changes in cerebral arterial waveforms and augmented peak diastolic and mean MCA flow velocities on TCD in 5 healthy subjects.

Background and Purpose: We aimed to investigate the feasibility and therapeutic effect of external counterpulsation (ECP) in ischemic stroke., Methods: The trial was a randomized, crossover, assessment-blinded, proof-of-concept trial. ECP treatment consisted of 35 daily 1-hour sessions. Patients were randomized to either early (ECP weeks 1 to 7 and no ECP weeks 8 to 14) or late group (no ECP weeks 1 to 7 and ECP weeks 8 to 14). Primary outcomes were an overall change in National Institutes of Health Stroke Scale (NIHSS) and cerebral blood flow estimated by color velocity imaging quantification. Secondary outcomes were change in NIHSS, color velocity imaging quantification, favorable functional outcome (modified Rankin scale, 0 to 2), and stroke recurrence at weeks 7 and 14, respectively., Results: Fifty patients were recruited. At week 7, there was a significant change in NIHSS (early 3.5 vs late 1.9; P=0.042). After adjusting for treatment sequence, ECP was associated with a favorable trend of change in NIHSS of 2.1 vs 1.3 for non-ECP (P=0.061). Changes of color velocity imaging quantification were not significant but tended to increase with ECP. At week 14, a favorable functional outcome was found in 100% of early group patients compared to 76% in the late group (P=0.022)., Conclusions: ECP is feasible for ischemic stroke patients with larger artery disease.

Background: Despite the rapid progress in stroke prevention, effective acute stroke treatment except for thrombolysis is still lacking. Hypoperfusion is related to unfavorable functional outcome, further strokes and long-term mortality. Therefore, the need for a safe and effective way of increasing the cerebral blood flow seems obvious. Currently, there is a growing body of evidence to suggest that external counterpulsation (ECP) may enhance the blood supply to the brain and thus may be beneficial to patients with ischemic stroke., Methods: A MEDLINE search in combination with a search for papers in Chinese literature in the Wan Fang and China Academic Journal databases was carried out., Results: Preliminary investigations suggested that ECP may improve the clinical outcome of stroke patients. However, well-designed clinical studies exploring the therapeutic effects of ECP in ischemic stroke are very limited., Conclusions: Randomized-controlled trials with a large sample size are needed to further define the efficacy and safety of ECP in acute stroke management. Future studies should provide insight into the value of ECP in ischemic stroke as well as its possible mechanisms., ((c) 2008 S. Karger AG, Basel.)

Although the Virchow's triad on thrombosis includes reduced blood flow as a factor, there has been relatively little data on the importance of total cerebral blood flow on the risk of subsequent stroke. In the current study, we investigate whether total cerebral blood flow helps predict stroke recurrence. Extracranial arterial blood flow volume estimated by color velocity imaging quantification ultrasound (CVIQ) is an index of cerebral blood flow measurement. We performed a cohort study of 210 consecutive acute stroke patients. Patients were studied with transcranial Doppler and duplex ultrasound for intra- and extracranial large artery disease within 3 days of symptom onset. The association between the risk of recurrent stroke and CVIQ was analyzed with Cox proportional hazards model. Thirty-nine patients (17.7%) developed an ischemic stroke during a mean follow-up of 47.5 months. The mean extracranial blood flow volume was significantly lower for patients who had a recurrent stroke than those without (594.4+/-130.3 versus 683.8+/-176.9 mL/min; P=0.003). In a Cox proportional hazards model adjusting for potential confounding variables, extracranial blood flow volume (hazard ratio (HR) for lowest tertile, 4.1; 95% confidence interval (CI), 1.5 to 11.0) along with male sex (HR, 2.5; 95% CI, 1.3 to 5.1), diabetes (HR, 2.5; 95% CI, 1.2 to 5.0) and large artery stenosis (HR, 2.2; 95% CI, 1.1 to 4.4) were independent predictors for stroke recurrence. Our data indicated that patient with low amount of blood flow to the brain is at risk of recurrent stroke.

Background and Purpose: The relationships between cerebral vasomotor reactivity (CVR) and white matter lesions (WMLs) were investigated mainly in patients with carotid stenosis. We aimed to study the relationship in asymptomatic elderly subjects without large artery occlusive disease., Methods: A total of 33 elderly individuals (mean age was 76.2 years) who were free from neurological deficit or cognitive impairment were studied. Bilateral mean blood flow velocity was measured in the middle cerebral artery using a 2-MHz pulsed transcranial Doppler (TCD) system together with intravenous administration of acetazolamide as vasodilatory stimuli. WMLs on a fluid-attenuated inversion recovery (FLAIR) sequence of MRI were classified into two categories: subcortical deep white matter hyperintensity (SDWMH) and periventricular hyperintensity (PVH). The lesions in each category were then divided into three grades (grade 0-I, grade II, grade III) according to the Fazekas scale., Results: CVR was inversely associated with the extent of SDWMH and PVH. The differences in CVR were statistically significant among different severity of WMLs: for SDWMH (70%+/- 10% in grade 0-I, 60%+/- 10% in grade II, and 40%+/- 10% in grade III, P < .001); for PVH (80%+/- 10% in grade 0-I, 60%+/- 10% in grade II, and 40%+/- 10% in grade III, P < .001)., Conclusions: Impaired CVR is related to the extent of WMLs in asymptomatic elderly individuals without large artery stenosis. The findings in our study suggest that dysfunction of cerebral vascular autoregulation might be an important factor in the development of WMLs in the asymptomatic elderly without large artery occlusive disease.

Traditionally hypoperfusion and embolism are considered separate important causes of stroke in patients with arterial occlusive disease. However, although hypoperfusion and embolism differ in mechanisms and location, they generally coincide in severe obstructive lesions and cause washout disturbances of embolism in low perfusion territories distal to stenosis. Unless the collateral blood supply is sufficient to prevent ischemia, multiple remote spot-like infarctions occur within the hypoperfused brain territory. In border-zone distributed infarction - long suspected to result from hemodynamic compromise alone - complementary interaction of embolisation and hypoperfusion territories has to be considered. Thus hypoperfusion with embolism or embolism alone are the most common explanations for stroke, the former often associated with less severe clinical deficits than the latter., (Copyright 2006 S. Karger AG, Basel.)

Objective: To show whether there is any association between the development of neurologic symptoms and the total cerebral blood flow volume documented by color velocity imaging in patients with carotid stenosis that develops after radiotherapy., Methods: Twenty-three patients with nasopharyngeal carcinoma (4 female and 19 male; age range, 39-69 years; mean age, 55.6 years) and major extracranial carotid stenosis underwent color velocity imaging. In this group, 8 patients had symptoms of a stroke or transient ischemic attack, and the other 15 patients were asymptomatic. The color velocity imaging results in the symptomatic group were then compared with those in the asymptomatic group., Results: The cerebral blood flow in the symptomatic group was significantly lower than that in the asymptomatic group (224.1 +/- 89.0 versus 532.5 +/- 89.0 mL/min; P = .001)., Conclusions: Cerebral blood flow as measured by color velocity imaging was lower in the symptomatic group. There is an association between the development of neurologic symptoms and blood flow volume.