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A Patient-Specific Analysis Framework for Assessing Stroke Risk in Pediatric Moyamoya Disease

Award Number: R03NS110442
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2018
PERIOD OF PERFORMANCE END DATE: 08/31/2021

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A Patient-Specific Analysis Framework for Assessing Stroke Risk in Pediatric Moyamoya Disease - PROJECT SUMMARY: Pediatric MoyaMoya Disease (MMD) is a cerebrovascular disease characterized by progressive narrowing of the major arteries in the Circle of Willis (CoW), leading to recurring ischemic and hemorrhagic stroke. Clinical strategies to prevent or reverse vessel occlusion through medical management are not available. Neurosurgical interventions are used to augment blood flow to the affected region and avert future stroke events; but carry the risk of perioperative stroke, infection and intracranial hemorrhage. Treatment is an absolute necessity however, since a morbidity rate of > 70% in untreated patients is currently realized. While atypical vessel straightening, narrowing and collateralizations are commonly observed on the CT- angiograms, there is a lack of understanding how these characteristic vascular alterations affect local hemodynamics and disease progression, and there has been no study of the effect of surgical interventions on future stroke events. Computational simulations, adjusted with patient-specific attributes, have been successfully used in other pathological conditions to predict local hemodynamics, potentially informing therapy and interventional strategies. The long-term objective is therefore to develop a predictive patient-specific analysis framework to assess stroke risk in pediatric MMD patients treated by surgical intervention, and delineate scenarios affecting disease severity. In a pilot study involving ACTA2(-/-) knockout mouse models, which develop many of the phenotypic features of MMD, computational fluid dynamic analysis of the authentic CoW vasculature was performed applying state-of-the-art isogeometric analysis technology. Locations of critical wall shear rate (above the coagulation limit) that were at a greater risk of clot formation were predicted. Results show that occlusion in one of the major arteries in the CoW increases stroke risk in mouse models of MMD. If a similar or equivalent behavior is realized in the human condition, it could have profound implications for patient care. The goal for the proposed research is to perform 3D patient-specific analysis on a pilot cohort (n=6) of human CoW to identify susceptible regions that could evolve into severe stenosis or complete vessel occlusion, leading to stroke in pediatric MMD patients, and compare the predictions to follow up clinical observations. The central hypothesis is that the simulations will accurately predict the occurrence and location of the stroke. Once the analysis framework is established and the predictive capability assessed in this pilot; a comprehensive study on a population of at least 50 cases will be performed to reliably assess the utility of computational predictions of stroke risk in pediatric MMD patients. The proposed research is significant, as it will provide predictive insight into complex interplay between vascular geometry and hemodynamic environment altered by MMD in a patient-specific sense. If confirmed in a larger cohort, the presented analysis framework could enable clinicians to predict patients at risk of stroke prior to the imaging assessments of severe hemodynamic impairment/collaterization that is used currently, potentially leading to earlier intervention.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2019	TEXAS HEART INSTITUTE	6770 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	3/17/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $81,500 )
2019	2019	TEXAS HEART INSTITUTE	6770 BERTNER AVE MC3 117	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	8/21/2019	NON-COMPETING CONTINUATION	$81,500
														Subtotal = $81,500

Issue Date FY: 2018 ( Subtotal = $81,500 )
2018	2018	TEXAS HEART INSTITUTE	6770 BERTNER AVE MC3 117	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/21/2018	NEW	$81,500
														Subtotal = $81,500

Grand Total All Awards = $163,000

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A Patient-Specific Analysis Framework for Assessing Stroke Risk in Pediatric Moyamoya Disease

Award Number: R03NS110442

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/30/2018

PERIOD OF PERFORMANCE END DATE: 08/31/2021

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