Collateral Supply in Preclinical Cerebral Stroke Models

Enhancing the collateral blood supply during the acute phase of cerebral ischemia may limit both the extension of the core infarct, by rescuing the penumbra area, and the degree of disability. Many imaging techniques have been applied to rodents in preclinical studies, to evaluate the magnitude of collateral blood flow and the time course of responses during the early phase of ischemic stroke. The collateral supply follows several different routes at the base of the brain (the circle of Willis) and its surface (leptomeningeal or pial arteries), corresponding to the proximal and distal collateral pathways, respectively. In this review, we describe and illustrate the cerebral collateral systems and their modifications following pre-Willis or post-Willis occlusion in rodents. We also review the potential pharmaceutical agents for stimulating the collateral blood supply tested to date. The time taken to establish a collateral blood flow supply through the leptomeningeal anastomoses differs between young and adult animals and between different species and genetic backgrounds. Caution is required when transposing preclinical findings to humans, and clinical trials must be performed to check the added value of pharmacological agents for stimulating the collateral blood supply at appropriate time points. However, collateral recruitment appears to be a rapid, beneficial, endogenous mechanism that can be stimulated shortly after artery occlusion. It should be considered a treatment target for use in addition to recanalization strategies.

Predictive Value of CT Perfusion Imaging on the Basis of Automatic Segmentation Algorithm to Evaluate the Collateral Blood Flow Status on the Outcome of Reperfusion Therapy for Ischemic Stroke

Our objective was to study the predictive value of CT perfusion imaging based on automatic segmentation algorithm for evaluating collateral blood flow status in the outcome of reperfusion therapy for ischemic stroke. All data of 30 patients with ischemic stroke reperfusion in our hospital were collected and examined by CT perfusion imaging. Convolutional neural network (CNN) algorithm was used to segment perfusion imaging map and evaluate the results. The patients were grouped by regional leptomeningeal collateral score (rLMCs). Binary logistic regression was used to analyze the independent influencing factors of collateral blood flow on brain CT perfusion. The modified Scandinavian Stroke Scale was used to evaluate the prognosis of patients, and the effects of different collateral flow conditions on prognosis were obtained. The accuracy of CNN segmentation image is 62.61%, the sensitivity is 87.42%, the similarity coefficient is 93.76%, and the segmentation result quality is higher. Blood glucose (95% CI = 0.943, P = 0.028 ) and ischemic stroke history (95% CI = 0.855, P = 0.003 ) were independent factors affecting the collateral blood flow status of stroke patients. CBF (95% CI = 0.818, P = 0.008 ) and CBV (95% CI = 0.796, P = 0.016 ) were independent influencing factors of CT perfusion parameters. After 3 weeks of onset, the prognostic function defect score of the good collateral flow group (11.11%) was lower than that of the poor group (41.67%) ( P < 0.05 ). The automatic segmentation algorithm has more accurate segmentation ability for stroke CT perfusion imaging and plays a good auxiliary role in the diagnosis of clinical stroke reperfusion therapy. The collateral blood flow state based on CT perfusion imaging is helpful to predict the treatment outcome of patients with ischemic stroke and further predict the prognosis of patients.

Abstract 1122‐000181: Collateral Circulation in Ischemic Stroke is Not Determined by Anatomical Variants of the Cerebral Arteries

Introduction : In acute ischemic stroke, collateral circulation determines tissue fate and treatment results. The aim of this study was to evaluate the role of anatomical variations of the Circle of Willis (CoW) in formation of cerebral collateral blood flow in patients with acute M1 occlusion. Methods : This study was a retrospective assessment of radiological examinations of patients with stroke due to middle cerebral artery M1 segment occlusion. All patients underwent mechanical thrombectomy from January 2015 until March 2021. The anatomy of the CoW was assessed on initial CT‐angiography and DSA. CTA was utilized to grade cranial collateral vasculature status and cortical vein opacification score (COVES). Non‐contrast CT scans and ASPECTS scores (using RAPID software) were used to determine the ischemic area. Results : A total of 100 patients were included in the analysis (58 females and 42 males, mean age: 71.6 +/‐ 13.9). We classified the anatomy of the CoW according to its continuity as a full circle. Patients with fully continuous CoW (n = 19) had worse COVES scores than those with CoW incomplete at both anterior and posterior portion (n = 9) (89% vs 68% with COVES 0–2, p = 0.179). No statistically significant results were found when comparing the enhancement of collaterals between these two groups (p = 0.390). The COVES scores were similar for patients with complete and incomplete anterior portions of CoW (77% vs 80% with COVES 0–2, p = 0.812). Patients with incomplete posterior portions of CoW had lower COVES scores than those with complete (80% vs 67% with COVES 0–2, p = 0.206). No statistically significant differences were discovered when comparing different types of the posterior communicating artery (adult, transitional and fetal). Analysis of ischemic areas determined as ASPECTS scores pre‐ and post‐thrombectomy yielded no significant differences between any of the groups. Conclusions : Although certain variants of the CoW have been reported to increase the risk of ischemic stroke, our results show that the anatomy of CoW has no large effect on collateral blood flow during acute M1 occlusion. We presume that the greater role is played by pial arterioles than anatomical variants of major cerebral arteries in cerebral collateral circulation formation. Detailed knowledge about the factors that influence collateral blood flow is crucial as it may aid in identification of patients prone to worse outcomes of ischemic stroke. Anatomical variants of CoW do not play a major role in formation of cerebral collaterals.

Pathomorphological manifestations of vascular remodeling in the perifocal areas of ischemic cerebral infarction

Acute disorders of cerebral circulation remain one of the leading causes of death of patients throughout the world. Tissue recovery after a stroke is directly related to active revascularization, which is intensified in the peri-infarction area. Newly formed vessels contribute to the restoration of cellular metabolism in surviving neurons. The processes of vascular remodeling after stroke have been at the center of many clinical and morphological studies in recent years. The aim of the study. To study the processes of vascular remodeling and neoplasm of vessels in the perifocal areas of ischemic cerebral infarctions. Material and methods. The study researched the brain of 29 deceased patients with hemispheric infarctions with different periods of the disease: up to 3 days (n = 5), 6 days (n = 5), 9-12 (n = 10), 30 (n = 5), 45 days (n = 4). The object of the study was perifocal areas of cerebral infarction, as well as areas outside ischemic lesions. The studies were carried out using histological, morphometric and statistical techniques. Results. Studies have shown that in the perifocal areas of cerebral infarction within 3 days from the onset of the disease, the morpho-functional state of the microvasculature was characterized by circulatory and hemocoagulation disorders. Along with destructive changes in blood vessels, processes are directed to improve blood circulation in ischemic areas of the brain. Collateral blood flow increases, dilation of pial vessels is noted with a decrease in the Kernogan index. On the 6th day, the processes of angiogenesis and vasculogenesis are activated, which intensify in the subsequent stages of the disease. In the long term, the efficiency of collateral blood flow in the pial vessels decreases, reduction in the capillary network, and the lumen of large arteries is recalibrated. Conclusions. In the early stages of cerebral stroke (up to 3 days), increased blood circulation in the ischemic areas of the brain occurs due to increased collateral blood flow. From the 6th day, the processes of angiogenesis in the form of capillary budding and the processes of vasculogenesis intensify. In large arterioles, recalibration processes take place. After 30-45 days in the perifocal areas of cerebral infarction, a significant reduction of the capillary network is recorded, which is regarded as a reaction to a decrease in blood supply to the areas of organized infarction.

COMPARATIVE ANATOMY OF THE STRUCTURE OF THE VILLISIAN CIRCLE IN PERSONS WITH CEREBRAL CIRCULATION DISORDERS AND WITHOUT SIGNS OF PATHOLOGY

The study is devoted to the study of the anatomy of the Willis circle of people with and without cerebral circulation pathology. We studied 243 angiograms (men and women of different age groups from 18 to 72 years old). Of these, 120 patients had no signs of cerebrovascular pathology, 123 patients had various kinds of cerebral circulation disorders. Only in 32% of cases, when studying 120 MR-angiograms of persons without cerebral circulation disorders, a classical type of structure of the arterial bed was revealed. In 68% of the subjects, structural anomalies were found, namely: 23% hypoplasia of the anterior communicating artery, 21% aplasia or hypoplasia of one of the posterior communicating arteries, 17% combination of aplasia of the anterior communicating arteries and aplasia of one of the posterior communicating arteries, 4% aplasia of the anterior and both posterior connecting arteries, 3% parietal contact of both anterior cerebral arteries. A study of the Willis circle of patients with cerebrovascular pathology revealed: 2% have a classic variant of the structure, 53% have aplasia of one of the posterior communicating arteries, aplasia of both posterior communicating arteries 26%, 19% a variant in which aplasia of the anterior and posterior communicating arteries is combined. Based on the foregoing, the classical type of structure of the arterial circle of the brain is the most optimal option for ensuring collateral blood flow.

Abstract P321: The Cerebral Collateral Cascade: Rethinking the Assessment of Vascular Pathways in Acute Ischemic Stroke Patients

Background and Purpose: Robust collateral blood flow in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO) has been correlated with favorable outcomes. Collaterals are commonly assessed by the number of arteries present on non-invasive CT angiography (CTA) overlying ischemic brain, but blood transit from these arteries through the brain tissue and the venous drainage is not assessed by this technique. We hypothesized that a comprehensive imaging analysis of the cerebral collateral cascade (CCC) would predict clinical and radiological outcomes in patients with AIS-LVO patients. Materials and Methods: Multicenter retrospective cohort study of AIS-LVO patients undergoing thrombectomy triage. CCC was determined on pre-treatment imaging by scoring for pial arterial collaterals, tissue-level collaterals (TLC), and venous outflow. Pial arterial collaterals were determined by CTA (Tan scale), TLC were assessed on CT perfusion data using the Hypoperfusion Intensity Ratio, and venous egress was assessed on CTA using the cortical vein opacification score system. 3 groups were defined: CCC+ (good pial collaterals, TLC, and venous perfusion), CCC- (poor pial collaterals, TLC, and venous perfusion) and CCCmixed (reminder of patients). Primary outcome was a good functional outcome (modified Rankin Scale [mRS] 0-2 at 90 days). Secondary outcome was final infarct volume. Results: 647 patients met inclusion criteria: 176 CCC+, 345 CCCmixed and 126 CCC-. Multivariate ordinal logistic regression showed that CCC+ predicted good functional outcomes (mRS 0-2: OR=20.8 [95% CI 9.3-46.8]; p<0.001) compared to CCC- and CCCmixed. CCCmixed (β: 27.1, SE: 7.7; p<0.001) and CCC- (β: 86.6, SE: 9.9; p<0.001) profiles were associated with higher final infarct volumes after treatment compared to CCC+. Conclusion: Comprehensive assessment of the collateral blood flow cascade in AIS-LVO patients is a strong predictor of clinical and radiological outcomes in AIS-LVO patients.

Effect of Oxygen Extraction (Brush-Sign) on Baseline Core Infarct Depends on Collaterals (HIR)

Objectives: Baseline-core-infarct volume is a critical factor in patient selection and outcome in acute ischemic stroke (AIS) before mechanical thrombectomy (MT). We determined whether oxygen extraction efficiency and arterial collaterals, two different physiologic components of the cerebral ischemic cascade, interacted to modulate baseline-core-infarct volume in patients with AIS-LVO undergoing MT triage.Methods: Between January 2015 and March 2018, consecutive patients with an AIS and M1 occlusion considered for MT with a baseline MRI and perfusion-imaging were included. Variables such as baseline-core-infarct volume [mL], arterial collaterals (HIR: TMax &gt; 10 s volume/TMax &gt; 6 s), high oxygen extraction (HOE, presence of the brush-sign on T2*) were assessed. A linear-regression was used to test the interaction of HOE and HIR with baseline-core-infarct volume, after including potential confounding variables.Results: We included 103 patients. Median age was 70 (58–78), and 63% were female. Median baseline-core-infarct volume was 32 ml (IQR 8–74.5). Seventy six patients (74%) had HOE. In a multivariate analysis both favorable HIR collaterals (p = 0.02) and HOE (p = 0.038) were associated with lower baseline-core-infarct volume. However, HOE significantly interacted with HIR (p = 0.01) to predict baseline-core-infarct volume, favorable collaterals (low HIR) with HOE was associated with small baseline-core-infarct whereas patients with poor collaterals (high HIR) and HOE had large baseline-core-infarct.Conclusion: While HOE under effective collateral blood-flow has the lowest baseline-core-infarct volume of all patients, the protective effect of HOE reverses under poor collateral blood-flow and may be a maladaptive response to ischemic stroke as measured by core infarctions in AIS-LVO patients undergoing MT triage.