Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease

描述(申请人提供)：在美国，大约10%的中风是由颅内动脉粥样硬化病(IAD)引起的，在中国和东南亚，高达50%的中风是由IAD引起的，它可能是全球缺血性中风的最重要原因；此外，它具有在1年内早期复发的高达25%的风险。IAD的卒中机制尚不清楚，解开不同的缺血机制可能导致IAD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的血流限制、远端组织对受累区域的灌注和动脉间动脉栓塞术，以及这些机制之间的特定相互作用，来确定IAD患者卒中的机制。这项前瞻性的多中心研究将纳入175名最近有症状(7天)高级别(70%-99%)IAD的患者。将在指数事件发生后14天内对患者进行研究，使用以下先进的神经成像技术来阐明复发缺血的机制：定量磁共振成像以评估通过狭窄动脉的体积血流速度(目标1)；磁共振灌注加权成像以确定组织灌注，并通过经颅多普勒(TCD)评估受影响动脉远端的代偿性血流特征(目标2)；以及经颅多普勒(TCD)结合栓子信号监测以评估动脉与动脉之间的栓塞(目标3)。患者将接受标准化的医疗管理，并将监测其对血压、血脂和血糖控制的效果。主要的结果是在1年的随访期内狭窄的动脉区域复发；其次的结果是：a)在4-6周时在MRI上发现了新的无症状的缺血性病变，以及b)在1年的随访期内出现了短暂性脑缺血发作。

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.