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.

Public Health Relevance

Intracranial atherosclerotic disease (IAD) causes 10% of strokes in the US, is the most common cause of ischemic stroke in the China and Southeast Asia, and carries a high risk of early recurrence. Various mechanisms may be responsible for ischemia in IAD. This study will determine, through physiologic neuroimaging techniques, the possible mechanisms of ischemia. This study will lead to better stratification of those at high ris of ischemia, and to novel, rational and targeted interventions to prevent stroke recurrence.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS084288-01A1
Application #
8702343
Study Section
Special Emphasis Panel (ZRG1-BDCN-W (02))
Program Officer
Moy, Claudia S
Project Start
2014-03-01
Project End
2019-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
1
Fiscal Year
2014
Total Cost
$700,066
Indirect Cost
$182,658
Name
University of Miami School of Medicine
Department
Neurology
Type
Schools of Medicine
DUNS #
052780918
City
Coral Gables
State
FL
Country
United States
Zip Code
33146
Liebeskind, David S; Kosinski, Andrzej S; Lynn, Michael J et al. (2015) Noninvasive fractional flow on MRA predicts stroke risk of intracranial stenosis. J Neuroimaging 25:87-91