The goal of this work is to apply novel neuroimaging methods in patients with Moyamoya syndrome to test fundamental hypotheses regarding hemodynamic compensation, stroke history, and symptomatology. Moyamoya disease (MMD) has unknown etiology and is characterized by steno-occlusion of the supraclinoid internal carotid arteries and proximal branches, development of collateral vessels, and a high risk of stroke. Idiopathic MMD is relatively rare, however moyamoya syndrome (MMS), which can arise secondary to Down syndrome, sickle cell disease, atherosclerosis, and radiotherapy shares many phenotypical characteristics as idiopathic MMD, yet is observed much more frequently. Patients with MMS are at high risk for stroke, and compared with atherosclerotic disease where preferred treatment regimens are outlined by recent clinical trial results, optimal MMS therapies are less clear and may comprise medical management and/or surgical revascularization. Owing to the dynamic course of MMS, which includes a wide variation of progressive steno- occlusion, abnormal expression of endothelial growth factors and inflammatory proteins, hemo-metabolic disturbances, intimal vessel wall thickening, and neoangiogensis, there is a pressing clinical need to understand the pathophysiology of these processes, how they relate to symptomatology and stroke incidence, and ultimately may be used to stratify patients for therapy or guide development of novel pharmaceuticals. The critical barrier to achieving this rests with a lack of optimal methods that can be implemented for mapping and surveillance. Here, in adults and children with MMS, we propose to implement new MRI methods developed in our center to test focused hypotheses regarding (Aim 1) relationships between endothelial dysfunction, stroke incidence, and symptomatology;
(Aim 2) changes in vessel wall morphology, disease chronicity, and neurological symptoms;
and (Aim 3) oxygen extraction fraction response to surgical revascularization therapy. The short-term significance of this work is that it will improve our understanding of the physiological processes that underlie how tissue responds to proximal non-atherosclerotic steno-occlusion and revascularization, which will serve as a prerequisite for utilizing functional neuroimaging to stratify patients with MMS for appropriate therapy. The longer-term goal is to use this information to guide the development of novel pharmaceuticals or early screening procedures that may enable therapies to be titrated to patients prior to irreversible tissue damage. Finally, methods implemented are translatable to other vascular diseases, and findings should have broader relevance for discerning pathophysiological differences between atherosclerotic and non- atherosclerotic hemodynamic compensation mechanisms.

Public Health Relevance

Moyamoya syndrome (MMS) is a condition with unknown cause and is characterized by progressive narrowing of the blood vessels in the brain (i.e., stenosis), placing patients at high risk for stroke. Appropriate treatment of MMS requires understanding how the brain compensates for such stenosis, for instance through development of new blood vessels, and requires comprehensive and sensitive imaging methods. This work will develop and apply new magnetic resonance imaging methods to more thoroughly characterize these processes with the goal of improving our understanding of the most relevant indicators of disease severity, which could be used to titrate therapies to patients at highest risk for stroke.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS097763-01
Application #
9154661
Study Section
Acute Neural Injury and Epilepsy Study Section (ANIE)
Program Officer
Moy, Claudia S
Project Start
2016-07-01
Project End
2021-03-31
Budget Start
2016-07-01
Budget End
2017-03-31
Support Year
1
Fiscal Year
2016
Total Cost
$345,625
Indirect Cost
$126,875
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
079917897
City
Nashville
State
TN
Country
United States
Zip Code
37232
Watchmaker, Jennifer M; Juttukonda, Meher R; Davis, Larry T et al. (2018) Hemodynamic mechanisms underlying elevated oxygen extraction fraction (OEF) in moyamoya and sickle cell anemia patients. J Cereb Blood Flow Metab 38:1618-1630
Cogswell, Petrice M; Siero, Jeroen C W; Lants, Sarah K et al. (2018) Variable impact of CSF flow suppression on quantitative 3.0T intracranial vessel wall measurements. J Magn Reson Imaging 48:1120-1128
Lants, Sarah K; Watchmaker, Jennifer M; Juttukonda, Meher R et al. (2018) Treatment of Progressive Herpes Zoster-Induced Vasculopathy with Surgical Revascularization: Effects on Cerebral Hemodynamics. World Neurosurg 111:132-138
Cogswell, Petrice M; Davis, Taylor L; Strother, Megan K et al. (2017) Impact of vessel wall lesions and vascular stenoses on cerebrovascular reactivity in patients with intracranial stenotic disease. J Magn Reson Imaging 46:1167-1176
Ladner, Travis R; Donahue, Manus J; Arteaga, Daniel F et al. (2017) Prior Infarcts, Reactivity, and Angiography in Moyamoya Disease (PIRAMD): a scoring system for moyamoya severity based on multimodal hemodynamic imaging. J Neurosurg 126:495-503
Juttukonda, Meher R; Jordan, Lori C; Gindville, Melissa C et al. (2017) Cerebral hemodynamics and pseudo-continuous arterial spin labeling considerations in adults with sickle cell anemia. NMR Biomed 30:
Juttukonda, Meher R; Donahue, Manus J (2017) Neuroimaging of vascular reserve in patients with cerebrovascular diseases. Neuroimage :
Donahue, Manus J; Juttukonda, Meher R; Watchmaker, Jennifer M (2017) Noise concerns and post-processing procedures in cerebral blood flow (CBF) and cerebral blood volume (CBV) functional magnetic resonance imaging. Neuroimage 154:43-58
Talati, Pratik; Rane, Swati; Donahue, Manus J et al. (2016) Hippocampal arterial cerebral blood volume in early psychosis. Psychiatry Res Neuroimaging 256:21-25