The long-term goal of this work is to reduce the incident of stroke by identifying the most vulnerable patients using MRI scans. Currently roughly 1 of every 8 patient who have had an initial stroke from intracranial atherosclerosis disease (ICAD) will suffer a second stroke within a year. Patients who are likely to fail medical management have loss of cerebrovascular reserve, poor collateral arterial blood supply, and/or plaque that is vulnerable to rupture from active macrophage infiltration. Our goal is to identify vulnerable patients to inform the selection for new medical management protocols, stenting or stent-less angioplasty. We will develop a suite of new MRI scans and evaluate them in the intended patient population, comparing to reference standard CO2 Challenge CVR, HMPAO SPECT or direct imaging of active macrophages. Significance: ICAD is one of the most common causes of stroke worldwide and carries an extremely a high risk of recurrent stroke. ICAD patients with severe stenosis (70 to 99%) are at particularly high risk for recurrent stroke in the vascular territory of the stenosis (~12 to 20% within 12 months) despite treatment with aspirin, Plavix and management of risk factors (hypertension, smoking etc). The use of new, preventative treatment including angioplasty, new anti-platelet medication would benefit if the most vulnerable patient can be identified. Our imaging biomarkers will improve risk stratification for the of stroke in a vulnerable, high risk population. Innovation: We have developed time resolve MRI scans that are targeted to risk factor of stroke in ICAD: (1) Cardiac Gated ?Snapshot? images of transient changes in the cerebral vasculature in response to arterial pressure changes induced by the cardiac cycle. These changes are muted by a loss of cerebrovascular reserve a risk fact of stroke. (2) A new mathematical deconvolution algorithm based on linear time-invariant system theory to quantify perfusion supplied to a vascular bed through collateral arterial blood supply distal to a stenosis. (3) First ever high-resolution permeability of the intracranial arterial walls to identify macrophage infiltration. Scientific Rigor: The geometry of the human head and topology of the vasculature are unique, and we therefore perform all our studies in the intended patient population: humans with ICAD. To ensure scientific rigor, we will compare directly to reference standard values of CO2 cerebrovascular reserve, collateral arterial supply, and macrophage infiltration in plaques. Probability of Success: We have built a strong, multi-disciplinary team with a long track record of successful, collaborative neurovascular research. We believe this high probability of successful completion of the aims and high likelihood of clinical translation.
Intracranial atherosclerotic disease (ICAD), is one of the largest causes of stroke in the world. After surviving the initial ICAD stroke, roughly 1 of 8 will have a second devastating stroke within the next year. There is currently no way to determine who will fall victim to the second ICAD stroke. The use of Magnetic Resonance Imaging (MRI) is widespread in the evaluation of patients ICAD. Typically, MRI is used to locate the pathological narrowing (i.e. stenosis) of a blood vessel in the brain (intracranial stenosis/plaque). We will develop new MRI scans to measures a patients? ability to re-route around a stenosis, gradual loss of compensatory reserve and the likelihood that the stenosis ?throws off? a blood clot. It is these risk factors of an that could change the management to prevent an impending stroke. Our long term goal is to develop advance MRI scans that create images to better identify patients destine for a stoke, so that eventually the disease can be aggressively treated to PREVENT a secondary stroke.
