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 MRI protocol, in patients with symptomatic intracranial (IC) steno-occlusive disease. Recent studies have shown high two-year ischemic stroke rates in symptomatic patients with IC arterial stenosis. 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 has been 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. We have demonstrated the clinical utility of relatively new, noninvasive MRI approaches for assessing cerebrovascular reactivity (CVR), aCBV, and collateral CBF. We hypothesize that stroke risk can be more completely evinced from collective measurements of these parameters. Therefore, we propose to implement a novel, validated hemodynamic MRI protocol 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 variables as possible prognostic factors, we will quantify the extent to which two-year stroke risk is associated with hemodynamic compensation mechanisms. 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.

Public Health Relevance

Recent studies have shown high stroke rates in patients with intracranial arterial stenosis, however conflicting reports regarding how best to manage these patients. To better understand stroke risk in these patients, we propose to apply novel, noninvasive magnetic resonance imaging approaches to obtain a more comprehensive measure of tissue viability and the prevalence of vascular compensation strategies in this at-risk population. Results from this study are anticipated to provide new information regarding the mechanisms by which the brain compensates for arterial stenosis and to describe the relationship between these mechanisms and stroke risk with the overreaching aims of reducing stroke and long-term disability.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Special Emphasis Panel (ZRG1-DTCS-U (81))
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Janis, Scott
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Vanderbilt University Medical Center
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Talati, Pratik; Rane, Swati; Donahue, Manus J et al. (2016) Hippocampal arterial cerebral blood volume in early psychosis. Psychiatry Res 256:21-25
Roach, B A; Donahue, M J; Davis, L T et al. (2016) Interrogating the Functional Correlates of Collateralization in Patients with Intracranial Stenosis Using Multimodal Hemodynamic Imaging. AJNR Am J Neuroradiol 37:1132-8
Claassen, Daniel O; Dobolyi, David G; Isaacs, David A et al. (2016) Linear and Curvilinear Trajectories of Cortical Loss with Advancing Age and Disease Duration in Parkinson's Disease. Aging Dis 7:220-9
Strother, Megan K; Buckingham, Cari; Faraco, Carlos C et al. (2016) Crossed cerebellar diaschisis after stroke identified noninvasively with cerebral blood flow-weighted arterial spin labeling MRI. Eur J Radiol 85:136-42
Donahue, Manus J; Juttukonda, Meher R; Watchmaker, Jennifer M (2016) Noise concerns and post-processing procedures in cerebral blood flow (CBF) and cerebral blood volume (CBV) functional magnetic resonance imaging. Neuroimage :
Jordan, Lori C; Gindville, Melissa C; Scott, Allison O et al. (2016) Non-invasive imaging of oxygen extraction fraction in adults with sickle cell anaemia. Brain 139:738-50
Rane, Swati; Talati, Pratik; Donahue, Manus J et al. (2016) Inflow-vascular space occupancy (iVASO) reproducibility in the hippocampus and cortex at different blood water nulling times. Magn Reson Med 75:2379-87
Siero, Jeroen C W; Strother, Megan K; Faraco, Carlos C et al. (2015) In vivo quantification of hyperoxic arterial blood water T1. NMR Biomed 28:1518-25
Buck, Amanda K W; Elder, Christopher P; Donahue, Manus J et al. (2015) Matching of postcontraction perfusion to oxygen consumption across submaximal contraction intensities in exercising humans. J Appl Physiol (1985) 119:280-9
Talati, Pratik; Rane, Swati; Skinner, Jack et al. (2015) Increased hippocampal blood volume and normal blood flow in schizophrenia. Psychiatry Res 232:219-25

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