Intracranial atherosclerotic disease (ICAD) accounts for 7-10% of acute ischemic stroke with a substantial risk of recurrent stroke in a setting of severe intracranial stenosis, approaching 12-25% over 1-2 years despite medical management. However, a risk stratification scheme is not available to identify this susceptible population for targeted treatment trials when intervention with more aggressive medical management and/or endovascular angioplasty/stenting could limit complications of ischemic stroke. The unmet need that we plan to address is to develop and study MR imaging modalities that may characterize vulnerable inflammatory and/or hemodynamically significant intracranial plaques, stratifying the mechanisms and potential predictors of primary/recurrent ischemic stroke in ICAD. Recently, we have identified unique intracranial plaque characteristics as well as hemodynamic parameters using quantitative MR perfusion techniques to stage cerebrovascular reserve failure that are associated with symptomatic intracranial stenoses. We propose a prospective study to recruit asymptomatic and symptomatic patients with severe ICAD and longitudinally assess them with a comprehensive and novel MRI protocol: high resolution 3T MR imaging, ferumoxytol molecular imaging, dynamic contrast enhanced (DCE) MRI to quantify the transfer constant (Ktrans) of contrast plaque permeability, and dynamic susceptibility contrast (DSC) MR perfusion weighted imaging (MR- PWI) using the quantitative SCALE-PWI sequence. Our study hypothesis is that high resolution T1 plaque enhancement, T1/T2 plaque hemorrhage, early ferumoxytol uptake as a marker of macrophage infiltration/inflammation, intraplaque Ktrans permeability, and/or altered qCBF/qCBV perfusion based parameters with vascular territory analysis will assist in stratifying patient risk for thromboembolic versus hypoperfusion related ischemic complications respectively. This project aims to identify specific qualitative and quantitative thresholds with advanced high resolution, molecular, and functional MRI techniques that can be correlated to clinical presentations (asymptomatic, symptomatic, recurrent symptomatic), DWI infarct distributions (perforator, thromboembolic, hypoperfusion related infarcts), inflammatory blood markers, and clinical/imaging outcomes to inform an understanding of differential stroke mechanisms and to improve the selection of high risk ICAD patients who may be susceptible to primary or recurrent ischemic stroke despite aggressive medical management.

R21HL130969

2016-04-15

2020-03-31