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)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-DTCS-U (81))
Program Officer
Janis, Scott
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Vanderbilt University Medical Center
Schools of Medicine
United States
Zip Code
Siero, Jeroen C W; Hendrikse, Jeroen; Hoogduin, Hans et al. (2015) Cortical depth dependence of the BOLD initial dip and poststimulus undershoot in human visual cortex at 7 Tesla. Magn Reson Med 73:2283-95
Donahue, Manus J; Hussey, Erin; Rane, Swati et al. (2014) Vessel-encoded arterial spin labeling (VE-ASL) reveals elevated flow territory asymmetry in older adults with substandard verbal memory performance. J Magn Reson Imaging 39:377-86
Tietze, Anna; Blicher, Jakob; Mikkelsen, Irene Klaerke et al. (2014) Assessment of ischemic penumbra in patients with hyperacute stroke using amide proton transfer (APT) chemical exchange saturation transfer (CEST) MRI. NMR Biomed 27:163-74
Talati, Pratik; Rane, Swati; Kose, Samet et al. (2014) Increased hippocampal CA1 cerebral blood volume in schizophrenia. Neuroimage Clin 5:359-64
Donahue, Manus J; Rane, Swati; Hussey, Erin et al. (2014) ?-Aminobutyric acid (GABA) concentration inversely correlates with basal perfusion in human occipital lobe. J Cereb Blood Flow Metab 34:532-41
Raymond, J; Klink, R; Chagnon, M et al. (2014) Patients prone to recurrence after endovascular treatment: periprocedural results of the PRET randomized trial on large and recurrent aneurysms. AJNR Am J Neuroradiol 35:1667-76
Arteaga, Daniel F; Strother, Megan K; Faraco, Carlos C et al. (2014) The vascular steal phenomenon is an incomplete contributor to negative cerebrovascular reactivity in patients with symptomatic intracranial stenosis. J Cereb Blood Flow Metab 34:1453-62
Rane, Swati; Mason, Emily; Hussey, Erin et al. (2014) The effect of echo time and post-processing procedure on blood oxygenation level-dependent (BOLD) functional connectivity analysis. Neuroimage 95:39-47
Zuckerman, Scott L; Eli, Ilyas M; Morone, Peter J et al. (2014) Novel technologies in the treatment of intracranial aneurysms. Neurol Res 36:368-82
Strother, M K; Anderson, M D; Singer, R J et al. (2014) Cerebrovascular collaterals correlate with disease severity in adult North American patients with Moyamoya disease. AJNR Am J Neuroradiol 35:1318-24

Showing the most recent 10 out of 12 publications