Predicting Stroke Risk in ICAD With Novel MRI

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 inflammatory plaque that is vulnerable to rupture from active macrophage infiltration. Investigator's goal is to identify vulnerable patients to inform the selection for new medical management protocols or intervention with intracranial stenting or stent-less angioplasty. Investigators will develop a suite of novel MRI scans and evaluate them in the intended patient population, comparing to reference standard CO2 Challenge CVR, HMPAO SPECT, and to perform direct intracranial plaque molecular imaging for active macrophages. ICAD is one of the most common causes of stroke worldwide with 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 aggressive treatment with aspirin, clopidogrel (Plavix), management of risk factors (hypertension, smoking etc.), and lifestyle modification. The use of new, preventative treatments including angioplasty/stenting or new anti-platelet/anti-inflammatory medications would benefit the most vulnerable patients that may be able to be identified with investigator's MR imaging protocol prior to the failure of medical management. Investigator's novel MR imaging biomarkers will improve the risk stratification for ICAD related stroke and recurrent stroke in this vulnerable, high risk population. The Specific Aims of this study are: Specific Aim 1: To develop and validate an MRI scan protocol for quantification of cerebrovascular reserve that does not require externally administered physiologic stressors. Specific Aim 2: To develop and validate an MRI tissue perfusion protocol that can quantify the blood supplied through critical collateral arterial pathways. Specific Aim 3: To correlate dynamic contrast enhancement (Ktrans plaque permeability) and Fe- ferumoxytol uptake, as MRI biomarkers of inflammation (macrophage infiltration) in unstable ICAD plaques. Upon successful completion of this proposal Investigators will have developed three biomarkers of key risk factors for ICAD related stroke that will alter the management of patients in favor of earlier stroke prevention.