Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease

颅内动脉粥样硬化疾病早期复发的机制

基本信息

批准号：
9222819
负责人：
DAVID SIGMUND LIEBESKIND
金额：
$ 56.83万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-03-01 至 2019-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9222819
关键词：
Address Affect Arterial Fatty Streak Arteries Atherosclerosis Biological Markers Blood Pressure Blood Volume Blood flow Characteristics China Chronic Phase Clinical Trials Development Disease Distal Effectiveness Embolism Enrollment Event Financial compensation Functional disorder Image Image Analysis Imaging Techniques Impairment Individual Intervention Ischemia Ischemic Stroke Knowledge Lead Link Lipids Magnetic Resonance Magnetic Resonance Angiography Magnetic Resonance Imaging Medical Monitor Multicenter Studies Outcome Patients Perfusion Perfusion Weighted MRI Physiological Process Prospective Studies Recurrence Risk Risk stratification Signal Transduction Southeastern Asia Standardization Stenosis Stents Stratification Stroke Stroke prevention Techniques Territoriality Testing Therapeutic Embolization Tissues Transcranial Doppler Ultrasonography Transient Ischemic Attack Vasomotor base follow-up glycemic control hemodynamics high risk imaging biomarker improved indexing intracranial artery ischemic lesion neuroimaging non-invasive imaging novel prevent primary outcome prognostic prospective public health relevance secondary outcome specific biomarkers targeted treatment

项目摘要

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.

描述（申请人提供）：颅内动脉粥样硬化性疾病（IAD）在美国约占中风的 10%，在中国和东南亚约占中风的 50%，可能是全球缺血性中风的最重要原因；此外，其 1 年内早期复发的风险高达 25%。 IAD 中风的机制仍不清楚，阐明不同的缺血机制可能会导致风险分层和 IAD 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、受影响区域的远端组织灌注、动脉间栓塞以及这些因素之间的具体相互作用，确定 IAD 患者中风的机制。机制。这项前瞻性多中心研究将招募 175 名近期出现症状（<7 天）高级别（70-99%）IAD 的患者。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影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量（目标 1）；磁共振灌注加权成像确定组织灌注，并通过经颅多普勒 (TCD) 评估血管舒缩反应性，以评估受影响动脉远端区域的代偿血流特征（目标 2）；以及 TCD 和栓塞信号监测，以评估动脉间栓塞（目标 3）。患者将接受标准化医疗管理，并监测其对血压、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复发性卒中；次要结果是：a) 4-6 周时 MRI 上狭窄动脉分布中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中出现 TIA。