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Endovascular mechanical thrombectomy has significantly improved recovery in acute ischemic stroke (AIS). While traditional patient selection has relied on factors such as last known well and penumbra volume, emerging research highlights the importance of collateral circulation in influencing thrombectomy success. However, current methods to assess collateral circulation are often unreliable and lack standardization, limiting their integration into clinical decision-making and prompting the need for innovative approaches. This study introduces trans-clot manometry as a promising approach for quantitatively assessing collateral blood flow before thrombectomy. Two patients were included in this study: a 64-year-old female with a left M1 near-complete occlusion and an 81-year-old male with a left P1 occlusion. After receiving intravenous tenecteplase, each patient underwent emergent thrombectomy where intraoperative trans-clot manometry revealed significant trans-clot mean arterial pressure (MAP) gradients (66.7% for Patient 1 and 96.9% for Patient 2). Both patients had successful first-pass thrombectomy (Patient 1: TICI 3; Patient 2: TICI 3), with substantial clinical improvement (Patient 1: NIHSS 11 to 1; Patient 2: NIHSS 19 to 8). Intraoperative trans-clot manometry offers a simple yet powerful, objective, and generalizable measure of collateral circulation, applicable to a wide range of AIS cases regardless of clot location or vessel size. In addition, real-time correlations with heart-rate variability and radial artery pressures provide an intrinsic quality control, ensuring proper execution of the technique and accuracy of the resulting MAP gradient. Future research will focus on validating this approach, determining its generalizability, and establishing MAP gradient thresholds to enhance device selection and predict first-pass success., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Patients with acute ischemic stroke secondary to large vessel occlusions and good collaterals are frequently associated with favorable outcomes after mechanical thrombectomy, although poor outcomes are observed also in this subgroup. We aimed to investigate the factors associated with unfavorable outcomes (modified Rankin Scale3-6) in this specific subgroup of patients., Methods: In total, 219 patients (117 females) with anterior circulation stroke and good collaterals (American Society for Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology grades 3-4), treated by mechanical thrombectomy between 2016 and 2021 at our institution were included in this study. Clinical files and neuroimaging were retrospectively reviewed. Univariate and multivariate analyses were performed to identify the predictors of unfavorable outcomes in the overall population (primary endpoint). Secondary endpoints focused on the analysis of the predictors of unfavorable outcomes in the subgroup of successfully recanalized patients, mortality, and symptomatic intracerebral hemorrhages in the overall population., Results: Poor outcome was observed in 47% of the patients despite the presence of good collaterals. Older age ( p  < 0.001), higher baseline National Institute of Health stroke scale ( p  < 0.001), no intravenous thrombolysis administration ( p  = 0.004), > 3 passes ( p  = 0.01), and secondary transfers ( p  < 0.001) were associated with the primary endpoint. The multivariate analysis showed a predictive effect of modified treatment in cerebral infarction 2b-3 and of first pass effect on symptomatic intracerebral hemorrhage., Conclusions: Despite good collaterals, defined through the American Society for Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology scale, poor outcomes occurred in almost half of the patients. Patients with good collaterals not receiving intravenous thrombolysis were significantly associated with unfavorable outcomes, whereas first pass effect was not significantly correlated with clinical outcome in this specific cohort of patients. Different methods to assess collaterals should also be investigated., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Unfavorable venous outflow (VO) is associated with cerebral edema, which represents microvascular dysfunction. This study estimated the relationship between VO and microvascular function in acute ischemic stroke patients. We retrospectively included 102 MCA/ICA occluded patients with anterior circulation infarction who underwent reperfusion therapy between July 2017 and April 2022. Unfavorable VO was defined as a cortical vein opacification score of 0-3 and favorable VO as that of 4-6. The clinical characteristics, collateral status, microvascular integrity, and outcomes were compared between patients with favorable and unfavorable VO. Multivariate analysis and receiver operator characteristic (ROC) analysis were used. The patients with unfavorable VO had higher extravascular-extracellular volume fraction (Ve) in the infarct core and a lower percentage of robust arterial collateral circulation. ROC analysis revealed that Ve in the infarct core predicts unfavorable VO (AUC = 0.67, sensitivity = 65.08%, specificity = 69.23%). The higher Ve in the infarct core (odds ratio = 1.011, 95% CI = 1.000-1.021, P =  0.046) and poor arterial collateral flow (odds ratio = 0.102, 95% CI = 0.032-0.327, P  < 0.001) were independent predictors of unfavorable VO. This suggests that microvascular dysfunction may be one of the mechanisms underlying impaired VO., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Women, especially following menopause, are known to have worse outcomes following acute ischemic stroke. One primary postulated biological mechanism for worse outcomes in older women is a reduction in the vasculoprotective effects of estrogen. Using the INTERRseCT cohort, a multicentre international observational cohort studying recanalization in acute ischemic stroke, we explored the effects of sex, and modifying effects of age, on neuroradiological predictors of recanalization including robustness of leptomeningeal collaterals, thrombus burden and thrombus permeability. Ordinal regression analyses were used to examine the relationship between sex and each of the neuroradiological markers. Further, we explored both multiplicative and additive interactions between age and sex. All patients (n = 575) from INTERRseCT were included. Mean age was 70.2 years (SD: 13.1) and 48.5% were women. In the unadjusted model, female sex was associated with better collaterals (OR 1.37, 95% CIs: 1.01-1.85), however this relationship was not significant after adjusting for age and relevant comorbidities. There were no significant interactions between age and sex. In a large prospective international cohort, we found no association between sex and radiological predictors of recanalization including leptomeningeal collaterals, thrombus permeability and thrombus burden., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Field receives in-kind study medication from Bayer Canada and has received honoraria for advisory board work for HLS Therapeutics and Roche Canada. She is supported by a Sauder/Heart and Stroke Professorship from the University of British Columbia, the Vancouver Coastal Health Research Institute, the Michael Smith Institute for Health Research, and the Heart and Stroke Foundation of Canada. Dr. Menon reported holding stock and a patent for systems of triage in acute stroke in Circle NVI. Dr. Dowlatshahi reported receiving a grant from Heart & Stroke Foundation of Canada and personal fees from Apopharma, BMS, and Bayer. Dr Goyal reported receiving research grants to the University of Calgary by Stryker and Cerenovus and receiving consulting fees from Stryker, Mentice, Medtronic and Microvention. Dr. Demchuk reported receiving honoraria from Medtronic and holding stock and a patent in Circle NVI, a startup stroke imaging software company. Dr Hill reports grants from Covidien (Medtronic LLC), grants from Alberta Innovates, grants from Heart & Stroke Foundation of Canada, grants from Canadian Institutes of Health Research (Canadian Stroke Prevention Intervention Network), grants from University of Calgary (Hotchkiss Brain Institute), grants from Boehringer Ingelheim Canada, grants from NoNO, Inc, and grants from Biogen. In addition, Dr Hill has a patent to US Patent office Number: 62/086,077 and is Stock owner in Pure Web Incorporated and CircleNVI. Dr. Hill is a director of the Canadian Federation of Neurological Sciences, a not-for-profit group, is a director of the Canadian Stroke Consortium, a not-for-profit group, is a director of Circle NeuroVascular, and has received public grant support to the University of Calgary from Alberta Innovates Health Solutions, Canadian Institutes of Health Research, Heart & Stroke Foundation of Canada and National Institutes of Neurological Disorders and Stroke. The other authors report no conflicts.

Background and Purpose: Infarct growth rate (IGR) in acute ischemic stroke is highly variable. We sought to evaluate impact of symptom-reperfusion time on outcomes in patients undergoing mechanical thrombectomy (MT)., Methods: A prospectively maintained database from January,2012-August,2020 was reviewed. All patients with isolated MCA-M1 occlusion who achieved complete reperfusion(mTICI2C-3), had a witnessed symptom onset and follow-up MRI were included. IGR was calculated as final infarct volume (FIV)(ml)/symptom onset to reperfusion time(hours) and was dichotomized according to the median value into slow-(SP) versus fast-progressors (FP). The primary analysis aimed to evaluate the impact of symptom-reperfusion time on 90-day mRS in SP and FP. Secondary analysis was performed to identify predictors of IGR., Results: A total of 137 patients were eligible for analysis. Mean age was 63 ± 15.4 years and median IGR was 5.13ml/hour. SP(n = 69) had higher median ASPECTS, lower median rCBF<30% lesion volume, higher proportion of favorable collaterals and hypoperfusion intensity ratio (HIR)<0.4, higher minimal mean arterial blood pressure before reperfusion, and lower rates of general anesthesia compared to FP(n = 68). Symptom-reperfusion time was comparable between both groups. SP had higher rates of 90-day mRS0-2(71.9%vs.38.9%,aOR;7.226,95%CI[2.431-21.482],p < 0.001) and lower median FIV. Symptom-reperfusion time was associated with 90-day mRS0-2 in FP (aOR;0.541,95%CI[0.309-0.946],p = 0.03) but not in SP (aOR;0.874,95%CI[0.742-1.056],p = 0.16). On multivariable analysis, high ASPECTS and favorable collaterals in the NCCT/CTA model, and low rCBF<30% and HIR<0.4 in the CTP model were independent predictors of SP., Conclusions: The impact of symptom-reperfusion time on outcomes significantly varies across slow-versus fast-progressors. ASPECTS, collateral score, rCBF<30%, and HIR define stroke progression profile.

Despite successful recanalization, reperfusion failure associated with poor neurological outcomes develops in half of treated stroke patients. We explore here whether spreading depolarization (SD) is a predictor of reperfusion failure. Global forebrain ischemia/reperfusion was induced in male and female C57BL/6 mice (n = 57). SD and cerebral blood flow (CBF) changes were visualized with transcranial intrinsic optical signal and laser speckle contrast imaging. To block SD, MK801 was applied (n = 26). Neurological deficit, circle of Willis (CoW) anatomy and neuronal injury were evaluated 24 hours later. SD emerged after ischemia onset in one or both hemispheres under a perfusion threshold (CBF drop to 21.1 ± 4.6 vs. 33.6 ± 4.4%, SD vs. no SD). The failure of later reperfusion (44.4 ± 12.5%) was invariably linked to previous SD. In contrast, reperfusion was adequate (98.9 ± 7.4%) in hemispheres devoid of SD. Absence of the P1 segment of the posterior cerebral artery in the CoW favored SD occurrence and reperfusion failure. SD occurrence and reperfusion failure were associated with poor neurologic function, and neuronal necrosis 24 hours after ischemia. The inhibition of SD significantly improved reperfusion. SD occurrence during ischemia impairs later reperfusion, prognosticating poor neurological outcomes. The increased likelihood of SD occurrence is predicted by inadequate collaterals.

Background: In patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO), development of extensive early ischemic brain edema is associated with poor functional outcomes, despite timely treatment. Robust cortical venous outflow (VO) profiles correlate with favorable tissue perfusion. We hypothesized that favorable VO profiles (VO+) correlate with a reduced early edema progression rate (EPR) and good functional outcomes., Methods: Multicenter, retrospective analysis to investigate AIS-LVO patients treated by mechanical thrombectomy between May 2013 and December 2020. Baseline computed tomography angiography (CTA) was used to determine VO using the cortical vein opacification score (COVES); VO+ was defined as COVES ⩾ 3 and unfavorable as COVES ⩽ 2. EPR was determined as the ratio of net water uptake (NWU) on baseline non-contrast CT and time from symptom onset to admission imaging. Multivariable regression analysis was performed to assess primary (EPR) and secondary outcome (good functional outcomes defined as 0-2 points on the modified Rankin scale)., Results: A total of 728 patients were included. Primary outcome analysis showed VO+ (β: -0.03, SE : 0.009, p  = 0.002), lower presentation National Institutes of Health Stroke Scale (NIHSS; β: 0.002, SE : 0.001, p  = 0.002), and decreased time from onset to admission imaging (β: -0.00002, SE : 0.00004, p  < 0.001) were independently associated with reduced EPR. VO+ also predicted good functional outcomes (odds ratio (OR): 5.07, 95% CI: 2.839-9.039, p  < 0.001), while controlling for presentation NIHSS, time from onset to imaging, general vessel reperfusion, baseline Alberta Stroke Program Early CT Score, infarct core volume, EPR, and favorable arterial collaterals., Conclusions: Favorable VO profiles were associated with slower infarct edema progression and good long-term functional outcomes as well as better neurological status and ischemic brain alterations at admission.

Background: Computed tomography perfusion (CTP) has been increasingly used for patient selection in mechanical thrombectomy for stroke. However, previous studies suggested that CTP might overestimate the infarct size. The term ghost infarct core (GIC) has been used to describe an overestimation of the final infarct volumes by pre-treatment CTP of >10 ml., Aim: We sought to study the frequency and predictors of GIC., Methods: A prospectively collected mechanical thrombectomy database at a comprehensive stroke center between September 2010 and August 2020 was reviewed. Patients were included if they had a successful reperfusion (mTICI2b-3), a pre-procedure CTP, and final infarct volume measured on follow-up magnetic resonance imaging. Uni- and multivariable analyses were performed to identify predictors of GIC., Results: Among 923 eligible patients (median [IQR] age, 64 [55-75] years; NIHSS, 16 [11-21]; onset to reperfusion time, 436.5 [286-744.5] min), GIC was identified in 77 (8.3%) of the overall patients and in 14% (47/335) of those reperfused within 6 h of symptom onset. The median overestimation volume was 23.2 [16.4-38.3] mL. GIC was associated with higher NIHSS score, larger areas of infarct core and tissue at risk on CTP, unfavorable collateral scores, and shorter times from onset to image acquisition and to reperfusion as compared to non-GIC. Patients with GIC had smaller median final infarct volumes (10.7 vs. 27.1 ml, p < 0.001), higher chances of functional independence (76.2% vs. 55.5%, adjusted odds ratio (aOR) 3.829, 95% CI [1.505-9.737], p = 0.005), lower disability (one-point-mRS improvement, aOR 1.761, 95% CI [1.044-2.981], p = 0.03), and lower mortality (6.3% vs. 15%, aOR 0.119, 95% CI [0.014-0.984], p = 0.048) at 90 days. On multivariable analysis, time from onset to reperfusion ≤6 h (OR 3.184, 95% CI [1.743-5.815], p < 0.001), poor collaterals (OR 2.688, 95% CI [1.466-4.931], p = 0.001), and higher NIHSS score (OR 1.060, 95% CI [1.010-1.113], p = 0.018) were independent predictors of GIC., Conclusion: GIC is a relatively common entity, particularly in patients with poor collateral status, higher baseline NIHSS score, and early presentation, and is associated with more favorable outcomes. Patients should not be excluded from reperfusion therapies on the sole basis of CTP findings, especially in the early window.

For patients with symptomatic unilateral internal carotid artery (ICA) occlusion, impaired cerebrovascular reactivity (CVR) indicates increased stroke risk. Here, the role of collateral activation remains a matter of debate, whereas angio-anatomical collateral abundancy does not necessarily imply sufficient compensatory flow provided. We aimed to further elucidate the role of collateral activation in the presence of impaired CVR. From a prospective database, 62 patients with symptomatic unilateral ICA occlusion underwent blood oxygenation-level dependent (BOLD) fMRI CVR imaging and a transcranial Doppler (TCD) investigation for primary and secondary collateral activation. Descriptive statistic and multivariate analysis were used to evaluate the relationship between BOLD-CVR values and collateral activation. Patients with activated secondary collaterals exhibited more impaired BOLD-CVR values of the ipsilateral hemisphere (p = 0.02). Specifically, activation of leptomeningeal collaterals showed severely impaired ipsilateral hemisphere BOLD-CVR values when compared to activation of ophthalmic collaterals (0.05 ± 0.09 vs. 0.12 ± 0.04, p = 0.005). Moreover, the prediction analysis showed leptomeningeal collateral activation as a strong independent predictor for ipsilateral hemispheric BOLD-CVR. In our study, ipsilateral leptomeningeal collateral activation is the sole collateral pathway associated with severely impaired BOLD-CVR in patients with symptomatic unilateral ICA occlusion.

Tetralogy of Fallot (ToF) with pulmonary atresia (ToF-PA) is a complex congenital heart defect at the extreme end of the spectrum of ToF, with no antegrade flow into the pulmonary arteries. Patients differ with regard to the sources of pulmonary blood flow. In the milder spectrum of disease, there are confluent branch pulmonary arteries fed by ductus arteriosus. In more severe cases, however, the ductus arteriosus is absent, and the sole source of pulmonary blood flow is via major aortopulmonary collateral arteries (MAPCAs). The variability in the origin, size, number, and clinical course of these MAPCAs adds to the complexity of these patients. Currently, the goal of management is to establish pulmonary blood flow from the right ventricle (RV) with RV pressures that are ideally less than half of the systemic pressure to allow for closure of the ventricular septal defect. In the long term, patients with ToF-PA are at higher risk for reinterventions to address pulmonary arterial or RV-pulmonary artery conduit stenosis, progressive aortic root dilation and aortic insufficiency, and late mortality than those with less severe forms of ToF.

Leptomeningeal collateral supply is considered pivotal in steno-occlusive vasculopathy to prevent chronic microstructural ischaemic tissue damage. The aim of this study was to assess the alleged protective role of leptomeningeal collaterals in patients with unilateral high-grade steno-occlusive vasculopathy using quantitative (q)T2 mapping and perfusion-weighted imaging (PWI)-based collateral abundance. High-resolution qT2 was used to estimate microstructural damage of the segmented normal-appearing cortex. Volumetric abundance of collaterals was assessed based on PWI source data. The ratio relative cerebral blood flow/relative cerebral blood volume (rCBF/rCBV) as a surrogate of relative cerebral perfusion pressure (rCPP) was used to investigate the intravascular hemodynamic competency of pial collateral vessels and the hemodynamic state of brain parenchyma. Within the dependent vascular territory with increased cortical qT2 values ( P  = 0.0001) compared to the contralateral side, parenchymal rCPP was decreased ( P  = 0.0001) and correlated negatively with increase of qT2 ( P  < 0.05). Furthermore, volumetric abundance of adjacent leptomeningeal collaterals was significantly increased ( P  < 0.01) and negatively correlated with changes of parenchymal rCPP ( P  = 0.01). Microstructural cortical damage is closely related to restrictions of antegrade blood flow despite increased pial collateral vessel abundance. Therefore, increased leptomeningeal collateral supply cannot necessarily be regarded as a sign of effective compensation in patients with high-grade steno-occlusive vasculopathy.

We previously demonstrated that in the DEFUSE 3 trial, the union of the baseline core and the 24-h Tmax > 6 s perfusion lesion predicts the infarct volume at 24 h. Presently, we assessed if collateral robustness measured by the hypoperfusion intensity ratio (HIR) and cerebral blood volume (CBV) index accounts for the variance in these predictions. DEFUSE 3 patients underwent MRI/CT perfusion imaging at baseline and 24 h post-randomization. We compared baseline and follow-up HIR and CBV index across subgroups stratified by differences between predicted and observed 24-h infarct volumes. Of 123 eligible patients, 34 with 24-h infarcts larger than predicted had less favorable collaterals at baseline (HIR 0.43 vs. 0.32, p  = 0.006; CBV Index 0.78 vs. 0.85, p  = 0.001) and 24 h (HIR 0.56 vs. 0.07, p  = 0.004; CBV Index 0.47 vs. 0.73, p  = 0.006) compared to 71 patients with more accurate infarct volume prediction. Eighteen patients with 24-h infarcts smaller than predicted had similar baseline collateral scores but more favorable 24-h CBV indices (0.81 vs. 0.73, p  = 0.040). Overall, patients with 24-h infarcts larger than predicted had evidence of less favorable baseline collaterals that fail within 24 h, while patients with 24-h infarcts smaller than predicted typically had favorable collaterals that persisted for 24 h.

Portal hypertension is the main consequence of liver cirrhosis, leading to severe complications such as variceal hemorrhage, ascites or hepatic encephalopathy. As an attempt to decompress the portal venous system, portal flow is derived into the systemic venous system through spontaneous portosystemic shunts (SPSSs), bypassing the liver. In this review, we aim to provide an overview of the published reports in relation to the prevalence and physiopathology behind the appearance of SPSS in liver cirrhosis, as well as the complications derived from its formation and its management. The role of SPSS embolization is specifically discussed, as SPSSs have been assessed as a therapeutic target, mainly for patients with recurrent/persistent hepatic encephalopathy and preserved liver function. Furthermore, different aspects of the role of SPSS in liver transplantation, as well as in candidates for transjugular intrahepatic portosystemic shunt are reviewed. In these settings, SPSS occlusion has been proposed to minimize possible deleterious effects, but results are so far inconclusive., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Collateral circulation plays a pivotal role in acute ischemic stroke due to large vessel occlusion (LVO) and may be affected by multiple variables during sedation for endovascular therapy (EVT). We conducted detailed analyses of the GOLIATH trial to identify predictors of collateral circulation grade and infarct growth. We also modified the ASITN collateral grading scale and sought to determine its impact on clinical outcome and infarct growth. Multivariable analysis was used to identify predictors of collaterals and infarct growth. Ordinal analysis demonstrated nominal, but non-significant association between modified ASITN scale and infarct growth. Among all analyzed baseline clinical and procedural variables, the most significant predictors of infarct growth at 24 h were phenylephrine dose (estimate 6.78; p  = 0.014) and baseline infarct volume (estimate 0.93; p  = 0.03). The most significant predictors of worse collateral grade were mean arterial pressure (MAP) <70 mmHg (OR 0.35; p  = 0.048) and baseline infarct volume (OR 0.96; p  = 0.003). Hypotension during sedation for EVT for LVO negatively impacts collateral circulation, while higher pressor dose is a strong predictor of infarct growth. Avoidance of anesthesia-induced hypotension and consequent need for pressor therapy may prevent collateral failure and minimize infarct growth.

As a determinant of the progression rate of the ischaemic process in acute large-vessel stroke, the degree of collateralization is a strong predictor of the clinical outcome after reperfusion therapy and may influence clinical decision-making. Therefore, the assessment of leptomeningeal collateralization is of major importance. The purpose of this study was to develop and evaluate a quantitative and observer-independent method for assessing leptomeningeal collateralization in acute large-vessel stroke based on signal variance characteristics in T2*-weighted dynamic susceptibility contrast (DSC) perfusion-weighted MR imaging (PWI). Voxels representing leptomeningeal collateral vessels were extracted according to the magnitude of signal variance in the PWI raw data time series in 55 patients with proximal large-artery occlusion and an intra-individual collateral vessel index (CVI PWI ) was calculated. CVI PWI correlated significantly with the initial ischaemic core volume (rho = -0.459, p = 0.0001) and the PWI/DWI mismatch ratio (rho = 0.494, p = 0.0001) as an indicator of the amount of salvageable tissue. Furthermore, CVI PWI was significantly negatively correlated with NIHSS and mRS at discharge (rho = -0.341, p = 0.015 and rho = -0.305, p = 0.023). In multivariate logistic regression, CVI PWI was an independent predictor of favourable functional outcome (mRS 0-2) (OR = 16.39, 95% CI 1.42-188.7, p = 0.025). CVI PWI provides useful rater-independent information on the leptomeningeal collateral supply in acute stroke.

Background and Purpose: Computed tomography perfusion (CTP) and multiphase CT angiography (mCTA) help selection for endovascular treatment (EVT) in anterior ischemic stroke (AIS). Our aim was to investigate the ability of perfusion maps and collateral score to predict functional outcome after EVT., Patients and Methods: Patients with M1-middle cerebral artery occlusion, evaluated by mCTA and CTP and treated with EVT within six hours of onset, were enrolled. Perfusion parametric maps of cerebral blood flow (CBF), cerebral blood volume (CBV) and time to maximum of tissue residue function ( T max ) were generated; areas of altered perfusion were manually outlined to obtain volumes CBF v , CBV v , T max , v 16 - 25 s and T max , v 9 . 5 - 25 s . Diffusion-weighted imaging (DWI) at 24-36 hours was used to manually outline the ischemic core (volume: DWI v ). Collateral vessels were assessed on mCTA considering extent and delay of maximal enhancement (six-point scale). Functional outcome was evaluated by modified Rankin Scale score at three months. Volumes in good and poor outcome groups were compared by Wilcoxon rank-sum test t, and their discriminative ability for outcome was determined by receiver operating characteristic analysis. A logistic regression model, including T max , CBF and collaterals, was used to differentiate good and poor outcome., Results: Seventy-one patients (mean age 75 ± 11 years, range 45-99 years) were included. T max , v 16 - 25 s , T max , v 9 . 5 - 25 s , CBV v , CBF v and DWI v were statistically different between the two groups. CBF had the best discriminative value for good and poor outcome (area under the curve (AUC) 0.73; 64.5% sensitivity; 74.4% specificity); the logistic regression model might be promising (AUC 0.79, 64.5% sensitivity, 82.1% specificity)., Conclusions: In patients with AIS, the combined use of CTP and mCTA predicts functional outcome of EVT and might allow better selection.

Precision cerebrovascular health or individualized long-term preservation of the brain and associated blood vessels, is predicated on understanding, diagnosing, and tailoring therapies for people at risk of ischemic injury associated with stroke and vascular dementia. The associated imaging patterns are sculpted by the protective effect of the collaterome, the innate compensatory ability of the brain and vasculature to offset hypoperfusion when antegrade or normal arterial inflow pathways are compromised. Theranostics or rational and synchronous use of diagnostic studies in tandem with specific therapies to optimally guide patient outcomes in ischemic brain disorders may capitalize on the pivotal role of the collaterome. Understanding the functional impact of the collaterome across populations of individuals would advance translational science on the brain, while questions with immediate clinical implications may be prioritized. Big data and systematic analyses are necessary to develop normative standards, multimodal imaging atlases, and delineation of specific patterns to guide clinical management. Large-scale, systematic imaging analyses of the collaterome provide a platform for translational work on cerebral collateral circulation and hemodynamics and a theranostic framework with direct clinical implications. This article frames incipient research objectives to guide precision stroke medicine in coming years, building upon the collaterome concept in brain health.

Angiogenesis is a critical compensation route, which has been demonstrated in the brain following ischemic stroke; however, few studies have investigated angiogenesis in chronic intracranial atherosclerosis disease (ICAD). We used 68 Ga-NOTA-PRGD2 positron emission tomography/computed tomography based imaging to detect angiogenesis in chronic ICAD and to explore the factors that may have affected it. A total of 21 participants with unilateral severe chronic ICAD were included in the study. Of the 21 participants, 19 were men; the mean (SD) age was 52 (15) years. In 18 participants, we observed elevated 68 Ga-NOTA-PRGD2 uptake in the peri-infarct, subcortical, and periventricular regions of the lesioned side, with a higher 68 Ga-NOTA-PRGD2 SUV max compared to that in the contralateral hemisphere (0.15 vs. 0.06, p=0.001). The 18 F-FDG PET SUV max was significantly lower on the lesioned side (11.28 vs. 13.92, p=0.001). Subgroup analyses revealed that the recent group (<6 months) had a higher lesion-to-contralateral region ratio SUV max than the remote group (>6 months) (6.73 vs. 2.36, p<0.05). Our results provide molecular imaging evidence of angiogenesis in patients with severe chronic ICAD. Furthermore, the extent of angiogenesis in chronic ICAD may be affected by the post-qualified event time interval, and not by infarction itself or the severity of the arterial lesion.

Collaterals 2016 (third International Symposium on Collaterals to the Brain) was a multidisciplinary scientific conference focused on collateral circulation in acute ischemic stroke. Decisive challenges include generalizability of optimal triage and selection paradigms based on collateral status for definitive treatment of acute ischemic stroke, rapid dissemination of expert methods, and the urgent need to leverage networking opportunities for stroke science related to the hemodynamics of collaterals. The collaterome, or individual capacity to offset ischemia in the brain, and determination of a favorable collateral profile have become pivotal factors in consideration of the precision medicine of stroke decision-making. The conference convened over 50 invited faculty from around the world to connect on-site participants at a state-of-the-art facility with remote audiences in more than 22 countries and regions. The 2½-day program was structured into 40-min sessions devoted to key issues in translating the collaterome in acute stroke therapy across the globe. This unique forum of expertise emphasized the timely impact of collaterals on a monumental scale, encouraging maximal participation, rapid diffusion and added value of a diverse networking resource. The meeting format established a model geographical framework and innovative videoconferencing platform for future scientific conferences.

Background The purpose of this study was to determine the performance of computed tomography angiography (CTA) by using a scoring system to predict anterograde and collateral blood flow status in patients with symptomatic middle cerebral artery (MCA) stenosis with use of conventional angiography as standard reference. Methods We retrospectively identified all consecutive patients with unilateral symptomatic MCA stenosis in our center who underwent conventional angiography and CTA within 1 month. The anterograde and collateral blood flow (AnCo) scoring system consisted of anterograde score (AnS) and collateral score (CoS). Evaluation of the CTA images was done independently by two readers, based on the AnCo scoring system. The conventional angiography was assessed by using the Thrombolysis in Cerebral Infarction (TICI) and American Society of Interventional and Therapeutic Neuroradiology (ASITN/SIR) scoring system to determine the status of anterograde and collateral blood flow. Diagnostic performance of AnCo was evaluated by using the area under the receiver operating characteristic (ROC) curve. Results A total of 61 patients were included in the analysis with mean age of 53.4 ± 11.0 years. AnS demonstrated a strong correlation with TICI with statistical significance ( r = 0.786; p < 0.001). CoS had a modest yet statistically significant correlation with ASITN/SIR ( r = 0.574; p < 0.001). The ROC curve analysis for AnS demonstrated an area under the curve (AUC) of 0.894 ( p < 0.001) and the ROC curve analysis for CoS showed an AUC of 0.824 ( p < 0.001). Conclusions CTA was a potential method to evaluate anterograde and collateral blood flow status in patients with symptomatic unilateral MCA stenosis.

A noninvasive method for quantifying cerebral blood flow and simultaneously visualizing cerebral blood flow territories is vessel-encoded pseudocontinuous arterial spin labeling MRI. However, obstacles to acquiring such information include limited access to the methodology in clinical centers and limited work on how clinically acquired vessel-encoded pseudocontinuous arterial spin labeling data correlate with gold-standard methods. The purpose of this work is to develop and validate a semiautomated pipeline for the online quantification of cerebral blood flow maps and cerebral blood flow territories from planning-free vessel-encoded pseudocontinuous arterial spin labeling MRI with gold-standard digital subtraction angiography. Healthy controls (n = 10) and intracranial atherosclerotic disease patients (n = 34) underwent 3.0 T MRI imaging including vascular (MR angiography) and hemodynamic (cerebral blood flow-weighted arterial spin labeling) MRI. Patients additionally underwent catheter and/or CT angiography. Variations in cross-territorial filling were grouped according to diameters of circle of Willis vessels in controls. In patients, Cohen's k-statistics were computed to quantify agreement in perfusion patterns between vessel-encoded pseudocontinuous arterial spin labeling and angiography. Cross-territorial filling patterns were consistent with circle of Willis anatomy. The intraobserver Cohen's k-statistics for cerebral blood flow territory and digital subtraction angiography perfusion agreement were 0.730 (95% CI = 0.593-0.867; reader one) and 0.708 (95% CI = 0.561-0.855; reader two). These results support the feasibility of a semiautomated pipeline for evaluating major neurovascular cerebral blood flow territories in patients with intracranial atherosclerotic disease.

Focal hyperperfusion after acute ischaemic stroke could be of prognostic value depending upon its spatial localisation and temporal dynamics. Factors associated with late stage (12-24 h) perilesional hyperperfusion, identified using arterial spin labelling, are poorly defined. A prospective cohort of acute ischaemic stroke patients presenting within 4.5 h of symptom onset were assessed with multi-modal computed tomography acutely and magnetic resonance imaging at 24 ± 8 h. Multivariate logistic regression analysis and receiver operating characteristics curves were used. One hundred and nineteen hemispheric acute ischaemic stroke patients (mean age = 71 ± 12 years) with 24 h arterial spin labelling imaging were included. Forty-two (35.3%) patients showed perilesional hyperperfusion on arterial spin labelling at 24 h. Several factors were independently associated with perilesional hyperperfusion: good collaterals (71% versus 29%, P < 0.0001; OR = 5, 95% CI = [1.6, 15.7], P = 0.005), major reperfusion (81% versus 48%, P = < 0.0001; OR = 7.5, 95% CI = [1.6, 35.1], P = 0.01), penumbral salvage (76.2% versus 47%, P = 0.002; OR = 6.6, 95% CI = [1.8, 24.5], P = 0.004), infarction in striatocapsular (OR = 9.5, 95% CI = [2.6, 34], P = 0.001) and in cortical superior division middle cerebral artery (OR = 4.7, 95% CI = [1.4, 15.7], P = 0.012) territory. The area under the receiver operating characteristic curve was 0.91. Our results demonstrate good arterial collaterals, major reperfusion, penumbral salvage, and infarct topographies involving cortical superior middle cerebral artery and striatocapsular are associated with perilesional hyperperfusion.

We have recently shown that intracranial pressure (ICP) increases dramatically 24 h after minor intraluminal thread occlusion with reperfusion, independent of edema. Some of the largest ICP rises were observed in rats with the smallest final infarcts. A possible alternate mechanism for this ICP rise is an increase of cerebrospinal fluid (CSF) volume secondary to choroid plexus damage (a known complication of the intraluminal stroke model used). Alternatively, submaximal injury may be needed to induce ICP elevation. Therefore, we aimed to determine (a) if choroid plexus damage contributes to the ICP elevation, (b) if varying the patency of an important internal collateral supply to the middle cerebral artery (MCA), the anterior choroidal artery (AChA), produces different volumes of ischemic penumbra and (c) if presence of ischemic penumbra (submaximal injury) is associated with ICP elevation. We found (a) no association between choroid plexus damage and ICP elevation, (b) animals with a good internal collateral supply through the AChA during MCAo had significantly larger penumbra volumes and (c) ICP elevation at ≈24 h post-stroke only occurred in rats with submaximal injury, shown in two different stroke models. We conclude that active cellular processes within the ischemic penumbra may be required for edema-independent ICP elevation., (© The Author(s) 2016.)

Background: The steep, time-dependent loss of benefit from reperfusion in clinical trials is consistent with loss of penumbra over the early hours of ischemia, as observed in animal models. Human imaging studies, however, show persistent penumbra for up to 48 h. We investigated core and penumbra volumes and collateral status in relation to time after stroke onset within the first 6 h., Methods: Using data from three multimodal computer tomography-based studies in acute ischemic stroke patients <6 h after onset, we measured core and penumbra volumes, collateral status, and target mismatch (defined as core volume < 50 ml, perfusion lesion volume > 15 ml, mismatch ratio > 1.8). Patients were grouped by onset to imaging time (<3, 3-4.5, 4.5-6 h). We explored correlates of penumbra proportion by multivariable linear regression., Results: Analysis included 144 subjects. Across time epochs, neither proportions of penumbra (59%, 64%, 75% at <3, 3-4.5, >4. 5 h, respectively, p = 0.4) nor poor collaterals (15/56 (27%), 14/47 (30%), 4/15 (27%) at <3, 3-4.5, >4.5 h, p = 0.9) differed significantly. Penumbra proportion was not clearly related to time to imaging (R(2) = 0.003; p = 0.5) but a trend for divergent effects by collateral status was seen (slight increase in penumbra over time with good collaterals versus reduced with poor, interaction = 0.08). The proportion of patients with target mismatch did not vary by time (56%, 74%, and 67% at <3, 3-4.5, >4.5 h, p = 0.09)., Conclusions: In a cross-sectional sample imaged within 6 h, neither the proportions of penumbral tissue nor "target mismatch" varied by time from onset. A trend for reducing penumbra proportion only among those with poor collaterals may have pathophysiological and therapeutic importance., (© 2016 World Stroke Organization.)

ESCAPE is a prospective, multicenter, randomized clinical trial that will enroll subjects with the following main inclusion criteria: less than 12 h from symptom onset, age > 18, baseline NIHSS >5, ASPECTS score of >5 and CTA evidence of carotid T/L or M1 segment MCA occlusion, and at least moderate collaterals by CTA. The trial will determine if endovascular treatment will result in higher rates of favorable outcome compared with standard medical therapy alone. Patient populations that are eligible include those receiving IV tPA, tPA ineligible and unwitnessed onset or wake up strokes with 12 h of last seen normal. The primary end-point, based on intention-to-treat criteria is the distribution of modified Rankin Scale scores at 90 days assessed using a proportional odds model. The projected maximum sample size is 500 subjects. Randomization is stratified under a minimization process using age, gender, baseline NIHSS, baseline ASPECTS (8-10 vs. 6-7), IV tPA treatment and occlusion location (ICA vs. MCA) as covariates. The study will have one formal interim analysis after 300 subjects have been accrued. Secondary end-points at 90 days include the following: mRS 0-1; mRS 0-2; Barthel 95-100, EuroQOL and a cognitive battery. Safety outcomes are symptomatic ICH, major bleeding, contrast nephropathy, total radiation dose, malignant MCA infarction, hemicraniectomy and mortality at 90 days., (© 2014 World Stroke Organization.)

Thrombi, or clots, often occlude proximal segments of the cerebral arterial circulation in acute ischemic stroke. Thromboembolic occlusion or thrombi superimposed on atherosclerotic plaque are the principal focus of acute stroke therapies such as thrombolysis or thrombectomy. We review the imaging characteristics of thrombi on multimodal computed tomography and magnetic resonance imaging, angiography, and ultrasonography, summarizing recent studies that facilitate therapeutic decision-making from these noninvasive studies. Information about the location, size, and imaging characteristics can be ascertained using these techniques. Imaging findings in relation to occlusive thrombus have been correlated with clot pathology, response to therapeutic interventions, and clinical outcome. Diagnostic evaluation of occlusive thrombi on noninvasive studies now constitutes an integral component of acute stroke management., (© 2014 World Stroke Organization.)

Background: In stroke patients, collateral flow can rapidly be assessed on computed tomography angiography (CTA)., Aims: In this study, the impact of baseline collaterals on early outcome and risk of symptomatic intracerebral hemorrhages after systemic thrombolysis in patients with proximal arterial occlusions within the anterior circulation were analyzed., Methods: Collateralization scores were determined on the CT angiography source images (0 = absent; 1 ≤ 50%, 2 > 50% but <100%, and 3 = 100% collateral filling) of patients with distal intracranial carotid artery and/or M1 segment occlusions treated from 2008 to December 2011. A collateral score of 0 to 1 was designated as poor and 2 to 3 as good collateral vessel status. Outcome variables included in hospital mortality, favorable outcome at discharge (modified Rankin score ≤ 2), and rates of symptomatic intracerebral hemorrhage based on the European-Australasian Acute Stroke Study II definition., Results: Among 246 subjects (mean age of 74 years; median National Institutes of Health Stroke Scale N at admission 14), 205 patients (83%) had good collaterals, whereas 41 patients (17%) had poor collaterals, respectively. Patients with poor collaterals had significantly higher rates of in-hospital mortality (41% vs. 12%, P < 0·001), of symptomatic intracerebral hemorrhage (15% vs. 4·9%, P < 0·05) and had significantly lower rates of favorable early clinical outcome (0% vs. 28%, P < 0·001) compared with those with good collaterals. The grade of collateralization was independently associated with in-hospital mortality (P < 0·001), early clinical outcome (P < 0·01), and rates of symptomatic intracerebral hemorrhage (P < 0·01)., Conclusion: Patients with proximal arterial occlusions within the anterior circulation and poor baseline collaterals have a poor early functional outcome and high rates of symptomatic intracerebral hemorrhage after systemic thrombolysis. Since similar findings have also been reported after endovascular therapy, strategies to improve collateral blood flow should be assessed in this patient population., (© 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.)

Identification of patients with acute ischaemic stroke who could most benefit from arterial recanalization after endovascular treatment remains an unsettled issue. Although several classifications of collateral circulation have been proposed, the clinical role of collaterals is still debated. We evaluated the effect of the collateral circulation in relation to recanalization as a predictor of clinical outcome. Data were prospectively collected from 103 patients consecutively treated for proximal middle cerebral or internal carotid artery occlusion. The collateral circulation was evaluated with a novel semiquantitative-qualitative score, the Careggi collateral score (CCS), in six grades. Both CCS and recanalization grades (TICI) were analysed in relation to clinical outcome. A statistical analysis was performed to evaluate the effect of interaction between recanalization and collateral circulation on clinical outcome. Out of the 103 patients, 37 (36.3%) had poor collaterals, and 65 (63.7%) had good collaterals. Patients with good collaterals had lower basal National Institute of Health Stroke Scale (NIHSS), more distal occlusion, smaller lesions at 24h CT scan and better functional outcome. After multivariate analysis, the interaction between recanalization and collateral grades was significantly stronger as a predictor of good outcome (OR 6.87, 95% CI 2.11-22.31) or death (OR 4.66, 95%CI 1.48-14.73) compared to the effect of the single variables. Collaterals showed an effect of interaction with the recanalization grade in determining a favourable clinical outcome. Assessment of the collateral circulation might help predict clinical results after recanalization in patients undergoing endovascular treatment for acute ischaemic stroke.

We determined whether 7T magnetic resonance angiography (MRA) could be used for clearly observing microvessels in a clinically asymptomatic patient with steno-occlusion of the middle cerebral artery (MCA). We utilized 3T magnetic resonance imaging to obtain the brain images of a clinically asymptomatic patient and noted MCA steno-occlusion. In comparison with 3T MRA, 7T MRA could clearly delineate the microvessels, including lenticulostriate arteries and presumed collaterals, and our observation was comparable to that with conventional digital subtraction angiography. We report an interesting case of a clinically asymptomatic patient with MCA steno-occlusion.