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）在美国引起约10%的卒中，在中国和东南亚引起高达50%的卒中，可能是全球缺血性卒中的最重要原因;此外，其1年早期复发风险高达25%。网络成瘾患者脑卒中的发病机制尚不清楚，阐明不同的缺血机制可能有助于网络成瘾的危险分层和靶向治疗的发展。本研究的目的是通过专门评价通过狭窄动脉的血流限制、受影响区域的远端组织灌注和动脉间栓塞以及这些机制之间的特定相互作用，确定IAD患者卒中的机制。这项前瞻性多中心研究将招募175名近期有症状（<7天）的高级别（70 - 99%）IAD患者。将在指标事件发生后14天内对患者进行研究，采用以下先进的神经成像技术来阐明复发性缺血的机制：定量磁共振成像，以评估通过狭窄动脉的体积流速（目标1）;磁共振灌注加权成像以确定组织灌注，经颅多普勒（TCD）检测血管反应性，以评估受累动脉远端区域的代偿性血流特征（目的2）; TCD结合栓塞信号监测评价动脉-动脉栓塞（目的3）。患者将接受标准化的医疗管理，并将监测其对血压、血脂和血糖控制的有效性。主要结局是1年随访期间狭窄动脉区域内的复发性卒中;次要结局是：a）4 - 6周时MRI显示狭窄动脉分布区新发无症状缺血性病变，和B）1年随访期间狭窄动脉分布区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.