Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease
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 IADThis prospective multicenter study will enroll 175 patients with recently symptomatic (<7 days) high-grade IAD. Patients will be studied within 14 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 4-6 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 Start Date
Estimated Completion Date
No interventions cited
- Cardiology: Atherosclerosis/Lipids
- Internal Medicine: Atherosclerosis/Lipids,Neurology
- Neurology: Stroke/Vascular
- Family Medicine: Atherosclerosis/Lipids
- Brain Diseases
- Cerebrovascular Disorders
- Vascular Diseases
University of Miami -- 20140056
University of Miami
1. Stroke defined as symptoms lasting >24 hours and associated with imaging evidence of
acute ischemia in the distribution of the stenotic vessel on CT or MRI.
2. Eligible TIA defined as transient neurological symptoms lasting <24 hours, need to
1. accompanied by DWI abnormalities in the distribution of the stenotic artery or
2. multiple (>2), stereotyped events associated with unequivocal ischemic symptoms
(weakness, aphasia), and attributed to the symptomatic artery.
3. IAD should involve the intracranial carotid, middle cerebral, intracranial vertebral
or basilar arteries.
4. Stenosis 70-99% quantified by digital subtraction angiography (DSA) or the
combination of two non-invasive (CT angiography-CTA, MR angiography-MRA, transcranial
Doppler-TCD) tests. DSA is not required but will be used if obtained as part of
The criteria for 70-99% are:
1. CTA or DSA: measured 70-99% stenosis by WASID criteria (percent stenosis =
(1-[diameter stenosis/diameter normal]) x 100%.
2. MRA: presence of a flow gap.
3. TCD: mean flow velocity >100 cm/s for internal carotid and middle cerebral
arteries >80 cm/s for vertebral and basilar arteries.
5. Age >30 those 30-49 years of age must also have the presence of established
atherosclerotic disease in another vascular bed (coronary, extracranial carotid,
peripheral) or the presence of 2 or more risk factors (hypertension, diabetes
mellitus, hyperlipidemia, tobacco abuse within the last 2 years).
6. Enrollment within 7 days of symptom onset and completion of study imaging tests
within 14 days of index event (stroke or TIA).
7. Provide informed consent for participation in the study.
1. Other cause for stroke: atrial fibrillation, mitral stenosis, mechanical valve,
intracardiac thrombus or vegetation, dilated cardiomyopathy or ejection fraction
<30%, proximal extracranial carotid or vertebral stenosis >50%.
2. Contraindications to MRI, including MR-incompatible metallic implants, implanted
electronic devices, other potentially mobile ferromagnetic material, pregnancy (women
in fertile age should have a negative pregnancy test), lactation, morbid obesity, and
3. Renal impairment defined as either a creatinine level >1.5 mg/dL or a glomerular
filtration rate (GFR) <30 mL/min/1.73 m2.
4. Known allergy to gadolinium.
5. Unable to obtain informed consent by patient or legally authorized representative.
6. Severe behavioral or social problems that may interfere with the conduct of the
7. In the investigator's opinion, patient unlikely return for follow up visit and to
complete the study.
30 Years and older
Accepts Healthy Volunteers
Study Locations and Contact Information (9)
|Columbia University Medical Center - New York, New York||44.8 miles||Mitchell S Elkind MDfirstname.lastname@example.org|
|SUNYUniversity at Buffalo - Buffalo, New York||309.9 miles||Elad Levy MDemail@example.com|
|Medical University of South Carolina - Charleston, South Carolina||691.2 miles||Tanya Turan MDfirstname.lastname@example.org|
|Rush University Medical Center - Chicago, Illinois||748.9 miles||Sarah Y Song MD||312-563-2208||Sarah_Song@rush.edu|
|University of Alabama at Birmingham - Birmingham, Alabama||916.1 miles||Mark Harrigan MDemail@example.com|
|University of Florida - Gainesville, Florida||950.8 miles||Anna Khanna MDfirstname.lastname@example.org|
|University of Miami - Miami, Florida||1,141.0 miles||Iszet C Bustillo MPHemail@example.com|
|The University of Texas Southwestern Medical Center - Dallas, Texas||1,414.8 miles||Mark Johnson MD||214-648-7811||Mark.Johnson@UTSouthwestern.edu|
|UCLA - Los Angeles, California||2,499.3 miles||David S Liebeskind MDfirstname.lastname@example.org|