The objective of this study is to determine the mechanisms of stroke in patients with Intracranial Atherosclerotic Disease (IAD) by specifically evaluating limitations of antegrade flow through the stenotic artery, distal tissue perfusion to the affected territory, and artery-to-artery embolism. The hypothesis is that non-invasive imaging biomarkers that stratify stroke risk and distinguish mechanisms of IAD. This prospective multicenter study will enroll 175 patients with recently symptomatic high-grade IAD. Patients will be studied within 21 days of the index event (allowing appropriate time to arrange for diverse imaging modalities), with the following advanced neuroimaging techniques to elucidate mechanisms of recurrent ischemia: * Quantitative magnetic resonance imaging (QMRA) to assess volumetric flow rate through the stenotic artery. * Magnetic resonance perfusion weighted imaging (PWI-MRI) to determine distal tissue perfusion. * Vasomotor reactivity by Transcranial Doppler using the breath-holding technique (BHI-TCD) to assess compensatory flow characteristics to the territory distal to the affected artery; * Transcranial Doppler with embolic signal monitoring to evaluate artery-to-artery embolism that reflects plaque instability. 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; secondary outcomes are: a) new asymptomatic ischemic lesions on MRI in the distribution of the stenotic artery at 6-8 weeks, and b) transient ischemic attack (TIA) in the distribution of the stenotic artery during a 1-year follow-up period. Patients will be recruited at various sites that will be trained and certified on the imaging techniques employed. Raw imaging data will be interpreted centrally.
Study Type
OBSERVATIONAL
Enrollment
105
University of Alabama at Birmingham
Birmingham, Alabama, United States
UCLA
Los Angeles, California, United States
University of Florida
Gainesville, Florida, United States
Mayo Clinic Jacksonville
Jacksonville, Florida, United States
University of Miami
Miami, Florida, United States
Northwestern University Department of Radiology
Chicago, Illinois, United States
Rush University Medical Center
Chicago, Illinois, United States
Columbia University Medical Center
New York, New York, United States
Medical University of South Carolina
Charleston, South Carolina, United States
The University of Texas Southwestern Medical Center
Dallas, Texas, United States
Recurrent stroke in the territory of the symptomatic artery
Time to ischemic stroke in the territory of the symptomatic artery. Stroke is ascertained by the site neurologist and defined as new or worsening symptoms lasting \>24 hours and associated with imaging evidence of ischemia on CT or MRI in the distribution of the stenotic artery.
Time frame: 1 year
TIA in the territory of the stenotic artery
TIA in the territory of the stenotic artery is defined as transient neurological symptoms lasting \<24 hours and clearly related to the stenotic artery as per a neurologist.
Time frame: 1 year
Silent infarcts in the distribution of the stenotic artery
Silent infarcts will be assessed by comparing the DWI and FLAIR sequences at baseline and at 6-8 weeks. Silent infarcts are defined as new discrete lesions not apparent in the baseline images that are in the distribution of the stenotic artery, in the absence of the primary endpoint.
Time frame: 6-8 weeks
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