Vanderbilt Assessment of Multi-modal MRI in Patients At-Risk for Stroke With Intracranial Stenosis

The overall aim of this work is to assess the relationship between stroke risk and hemodynamic compensation strategies, as measured using a novel 3.0 Tesla (T) MRI protocol, in patients with symptomatic intracranial (IC) steno-occlusive disease. Recent studies have shown high two-year ischemic stroke rates of approximately 20% in symptomatic IC stenosis patients. Aggressive therapy for IC stenosis patients includes revascularization with angioplasty, IC stenting, or bypass, however identification of patients most likely to benefit from these more aggressive interventions, rather than medical management alone, has been problematic. Accurate measurements of hemodynamic compromise are likely required to better define stroke risk and guide treatment decisions. Specifically, in IC stenosis patients with compromised cerebral perfusion pressure (CPP), the extent of hemodynamic compromise reflects the autoregulatory capacity of vasculature to increase arterial cerebral blood volume (aCBV) and/or develop collaterals to supplement cerebral blood flow (CBF). The prevalence of CBF collateralization and aCBV autoregulation has been hypothesized to correlate uniquely with stroke risk, however the extent of this correlation is debated.

The critical barrier to stratifying stroke risk rests with a lack of (i) methodology for measuring multiple hemodynamic factors with high specificity and (ii) noninvasive approaches capable of monitoring longitudinal progression of impairment. The investigators have demonstrated the clinical utility of relatively new, noninvasive MRI approaches for assessing cerebrovascular reactivity (CVR), aCBV, and collateral CBF. These approaches have been optimized and feasibility assessed in healthy volunteers or isolated clinical studies, however comparatively little information is available regarding the relationship between these collective measures and stroke risk. Therefore, the investigators propose to complement established angiographic and structural imaging with more novel, validated hemodynamic measurements to assess tissue-level impairment and compensation strategies in patients with IC stenosis. Using a collective approach combining measurements of collateral CBF, aCBV and CVR in multiple brain regions, in conjunction with a statistical model incorporating the above parameters as possible prognostic factors, the investigators will quantify the extent to which two-year stroke risk is associated with hemodynamic compensation mechanisms in a population of symptomatic IC stenosis patients. The noninvasive and multi-faceted scope of this investigation is intended to expand the diagnostic stroke infrastructure and elucidate new hemodynamic prognostic indicators of stroke in this high-risk population.

Hypothesis (1). Changes in collateral CBF with hypercarbic stimulation positively correlate with two-year stroke incidence in symptomatic IC stenosis patients.

Aim (1). By separately magnetically labeling blood water in different feeding arteries (8), the investigators will use a tested vessel-selective arterial spin labeling (VS-ASL) approach and a calculated perfusion asymmetry index to noninvasively assess changes in collateral CBF patterns in patients with IC stenosis. IC stenosis (n=90) patients will be monitored for two years during which their known stroke incidence is 20%. Stroke incidence will be recorded and separate correlations between perfusion asymmetry and stroke risk will be assessed.

Hypothesis (2). Regionally reduced CVR, indicative of vascular steal phenomena, and elevated aCBV, will positively correlate with two-year stroke incidence in symptomatic IC stenosis patients.