Collateral Circulation in Acute Ischemic Stroke

描述（由申请人提供）：侧支循环是卒中病理生理学的一个基本组成部分，相对而言尚未被探索。本研究的主要目的是表征急性缺血性卒中侧支循环的性质，并评估通过侧支增加氧状态作为急性脑缺血的治疗策略。具体目的是：1)建立一个标准的急性大脑中动脉（MCA）卒中的小脑膜侧支血管造影分级量表；2)确定小脑膜侧支循环的准确MRI相关性；3)开发一种新的生理指标来衡量逆行小脑膜侧支血流的充分性——对MCA闭塞远端动脉血进行氧采样，并利用该指标来研究侧枝源性动脉血中缺氧的存在和可逆性；4)证明在急性MCA缺血患者中，血管内、颈动脉内给予水氧以增强经小脑膜侧支的氧输送是可行、安全的。而且可能有效。这些目标将在一项前瞻性、非随机、单中心、可行性、安全性和探索性疗效研究中得到解决，该研究对44例因MCA闭塞引起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。本研究的基本原理是治疗性地增加薄脑膜侧枝的氧含量可以减少缺血并改善微循环灌注。综合血管造影评价侧枝结合多模态MRI和氧采样将大大提高我们目前对急性缺血性卒中侧枝循环的理解。动态方面的侧支招募或侧支衰竭将记录序列MRI，包括扩散灌注序列和MRA。作为K23的提案，该奖项还将支持临床研究，神经影像学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，旨在使候选人成为以患者为导向的脑血管研究领域的完全独立和富有成效的研究者。拟议的研究将为未来的侧枝疗法时代奠定基础，为广泛的新兴侧枝增强策略的评估提供工具和方法。

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.