Collateral Circulation in Acute Ischemic Stroke

描述(申请人提供)：侧支循环是卒中病理生理学的一个基本组成部分，相对来说还没有被研究过。本研究的主要目的是描述急性缺血性卒中侧支循环的性质，并评价经络补氧作为急性脑缺血的治疗策略。其具体目标是：1)建立急性大脑中动脉(MCA)卒中患者软脑膜侧支循环的标准血管造影分级标准，2)确定准确的软脑膜侧支循环MRI相关性，3)开发一种新的生理指标，以判断大脑中动脉闭塞后远端动脉血氧浓度的充分性，并利用该方法研究侧支循环血中脱氧的存在和可逆性，以及4)证明血管内、颈动脉内给氧以增强急性大脑中动脉缺血患者通过软脑膜侧支的氧气输送是可行的、安全的和潜在有效的。这些目标将在一项前瞻性、非随机、单中心、可行性、安全性和探索性有效性研究中得到解决，研究对象为44名因大脑中动脉闭塞导致的急性缺血性卒中患者，在发病8小时内进行血管内水氧输送。这项研究的基本原理是，治疗性增加软脑膜侧支的含氧量可能会减少缺血并改善微循环灌流。对侧支循环进行全面的血管造影评估，结合多模式磁共振成像和氧气采样，将大大增强我们目前对急性缺血性卒中侧支循环的了解。侧支循环重建或侧支循环衰竭的动态方面将通过序列MRI记录下来，包括扩散-灌注序列和MRA。作为一项K23建议，该奖项还将支持临床研究、神经成像和脑流体力学方面的教学课程和指导互动培训的详细计划，旨在使候选人成为一名完全独立和富有成效的研究人员，面向患者的脑血管研究。这项拟议的研究将为未来的侧支疗法时代奠定基础，为评估一系列新出现的侧支增强战略提供工具和方法。

DESCRIPTION (provided by applicant): Collateral circulation is a fundamental component of stroke pathophysiology that has been relatively unexplored. The principal objective of this study is to characterize the nature of collateral circulation in acute ischemic stroke and to evaluate augmentation of oxygen status via collaterals as a therapeutic strategy for acute cerebral ischemia. The Specific Aims are 1) to establish a standard angiographic rating scale of leptomeningeal collaterals in acute middle cerebral artery (MCA) stroke, 2) to determine accurate MRI correlates of leptomeningeal collateral circulation, 3) to develop a novel physiologic measure for the adequacy of retrograde leptomeningeal collateral blood flow - oxygen sampling of arterial blood distal to MCA occlusion - and employ this measure to investigate the presence and reversibility of deoxygenation in collateral-derived arterial blood, and 4) to demonstrate that endovascular, intracarotid administration of aqueous oxygen to enhance oxygen delivery via leptomeningeal collaterals in patients with acute MCA ischemia is feasible, safe, and potentially efficacious. These Aims will be addressed in a prospective, nonrandomized, single-center, feasibility, safety, and exploratory efficacy study of endovascular aqueous oxygen delivery in 44 patients within 8 hours of onset of acute ischemic stroke due to MCA occlusion. The rationale for this study is that therapeutic augmentation of oxygen content in leptomeningeal collaterals may diminish ischemia and improve microcirculatory perfusion. Comprehensive angiographic evaluation of collaterals combined with multimodal MRI and oxygen sampling will considerably enhance our current understanding of collateral circulation in acute ischemic stroke. Dynamic aspects of collateral recruitment or collateral failure will be chronicled with serial MRI, including diffusion-perfusion sequences and MRA. As a K23 proposal, this Award will also support a detailed program of didactic coursework and mentored interactive training in clinical research, neuroimaging, and cerebral fluid mechanics, designed to enable the candidate to become a fully independent and productive investigator in patient-oriented cerebrovascular research. The proposed study will lay the foundation for a future era of collateral therapeutics, providing tools and approaches for the evaluation of a wide range of emerging collateral enhancement strategies.