Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease

描述（由申请人提供）：颅内动脉粥样硬化性疾病（IAD）在美国导致约10%的中风，在中国和东南亚高达50%的中风，可能是全球缺血性中风的最重要原因；此外，1年内早期复发的风险高达25%。缺血性脑卒中的发病机制尚不清楚，揭示不同的缺血性脑卒中发病机制可能导致缺血性脑卒中的风险分层和靶向治疗的发展。本研究的目的是通过具体评估狭窄动脉血流受限、远端组织灌注到受累区域、动脉对动脉栓塞以及这些机制之间的具体相互作用，来确定内源性内源性卒中患者的机制。这项前瞻性多中心研究将招募175名最近出现症状（<7天）的高级别（70- 99%）IAD患者。患者将在指数事件发生后的14天内进行研究，使用以下先进的神经影像学技术来阐明复发性缺血的机制：定量磁共振成像评估狭窄动脉的体积血流速率（目的1）；磁共振灌注加权成像确定组织灌注，经颅多普勒（TCD）血管舒缩反应性评估受影响动脉远端区域代偿血流特征（Aim 2）；TCD结合栓塞信号监测来评估动脉对动脉栓塞（Aim 3）。患者将接受规范化的医疗管理，并监测其对血压、血脂和血糖控制的效果。在1年的随访期间，主要结局是狭窄动脉范围内卒中复发；次要结果是：a) 4-6周狭窄动脉分布MRI上出现新的无症状缺血性病变，b) 1年随访期间狭窄动脉分布出现TIA。

DESCRIPTION (provided by applicant): Intracranial atherosclerotic disease (IAD) causes about 10% of strokes in the US, and up to 50% of strokes in China and Southeast Asia, and may be the most important cause of ischemic stroke worldwide; furthermore, it carries a risk of early recurrence as high as 25% at 1 year. The mechanisms of stroke in IAD remain unclear, and unraveling the distinct ischemic mechanisms may lead to risk stratification and the development of targeted therapies for IAD. The objective of this study is to determine the mechanisms of stroke in patients with IAD by specifically evaluating limitations of flow through the stenotic artery, distal tissue perfusion to the affected territory, and artery-to-artery embolim, as well as specific interactions between these mechanisms. This prospective multicenter study will enroll 175 patients with recently symptomatic (<7 days) high-grade (70- 99%) IAD. Patients will be studied within 14 days of the index event, with the following advanced neuroimaging techniques to elucidate mechanisms of recurrent ischemia: quantitative magnetic resonance imaging to assess volumetric flow rate through the stenotic artery (Aim 1); magnetic resonance perfusion weighted imaging to determine tissue perfusion, and vasomotor reactivity by transcranial Doppler (TCD) to assess compensatory flow characteristics to the territory distal to the affected artery (Aim 2); and TCD with embolic signal monitoring to evaluate artery-to-artery embolism (Aim 3). Patients will receive standardized medical management and its effectiveness on blood pressure, lipid, and glycemic control will be monitored. The primary outcome is recurrent stroke in the territory of the stenotic artery during a 1-year follow-up period; secondar outcomes are: a) new asymptomatic ischemic lesions on MRI in the distribution of the stenotic artery at 4-6 weeks, and b) TIA in the distribution of the stenotic artery during a 1-year follow-u period.