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基本组成部分，相对而言尚未研究。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，并评估通过侧支循环增强氧状态作为急性脑缺血的治疗策略。具体目的是：1）建立急性大脑中动脉（MCA）卒中中软脑膜侧支循环的标准血管造影评级量表，2）确定软脑膜侧支循环的准确MRI相关性，3）开发一种新的生理学测量方法，用于测量逆行软脑膜侧支血流的充足性-MCA闭塞远端动脉血的氧气采样-并采用该方法研究侧支动脉血中脱氧的存在和可逆性，以及4）证明血管内、颈动脉内给予水性氧以增强急性MCA缺血患者通过软脑膜侧支的氧输送是可行、安全和潜在有效的。这些目的将在一项前瞻性、非随机化、单中心、可行性、安全性和探索性有效性研究中得到解决，该研究在44例患者中进行，在MCA闭塞导致急性缺血性卒中发作后8小时内进行血管内水相氧输送。这项研究的基本原理是，治疗性增加软脑膜侧支的氧含量可以减少缺血和改善微循环灌注。综合血管造影评估侧支循环结合多模式MRI和氧气采样将大大提高我们目前对急性缺血性卒中侧支循环的理解。侧支募集或侧支衰竭的动态方面将通过系列MRI记录，包括弥散灌注序列和MRA。作为K23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详细教学课程和指导互动培训计划，旨在使候选人成为完全独立和富有成效的研究者以患者为导向的脑血管研究。这项研究将为未来的侧支疗法奠定基础，为评估各种新兴的侧支增强策略提供工具和方法。

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.