Description (from grant):
Significance: Moyamoya disease (MMD) is a severe cerebrovascular condition with unknown cause and confers a high risk of stroke; although historically observed in individuals of East Asian ancestry, MMD is now being reported with increasing frequency in North America. Stroke risk can be reduced when surgical revascularization procedures are performed, however, surgical response and disease trajectory can be highly variable, especially in the increasingly recognized North American phenotype. We will test fundamental hypotheses regarding how biomarkers of stroke risk, vascular steno-occlusion, and cerebrospinal fluid (CSF) motion inform treatment candidacy and pathogenesis in North American patients with idiopathic MMD. MMD is characterized by steno-occlusion of the supraclinoid internal carotid arteries and proximal branches, subsequent development of collateral vessels, and more than a seven-fold risk increase of stroke. MMD etiology remains unknown, animal disease models do not exist, biomarkers that may place patients at highest risk for stroke have not been conclusively established. Randomized clinical trials of surgical revascularization vs. medical management are unethical owing to the benefits that revascularization surgery confers for many patients, there is now a need to accurately identify factors that underlie the North American phenotype. Our goal is to develop personalized signatures of tissue physiology that inform neurological impairment and treatment response in these patients. To accomplish this, we will apply magnetic resonance imaging (MRI) and angiographic tools, on similar MRI and digital subtraction angiography equipment at two of the largest North American MMD treatment centers (VU and Johns Hopkins). We propose to evaluate generalizable and pre-surgical biomarkers of ischemic symptomatology, surgical response, and cerebral ischemia to help characterize the spectrum and hemodynamic origins of impairment in North American MMD patients undergoing these indirect surgical revascularizations. Additionally, we will explore new directions in this field, whereby we will evaluate whether neuroimaging markers of aberrant neurofluid flow provide indicators of impaired cortical hemodynamics. Successful completion should provide new technologies that can expand the diagnostic and surveillance imaging infrastructure for the growing number of patients with idiopathic MMD.