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BBB Permeability Imaging in CADASIL

Award Number: R01NS114382
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: 02/01/2020
PERIOD OF PERFORMANCE END DATE: 01/31/2025

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BBB Permeability Imaging in CADASIL - Project Summary/Abstract The purpose of this US-China Biomedical Research Collaboration project is to understand the role of the blood-brain barrier (BBB) in the pathogenesis of cerebral small vessel disease (SVD) and to validate BBB permeability imaging as an early marker of SVD. SVD is a major cause of stroke, white matter (WM) disease and dementia, but the mechanisms underlying brain damage and cognitive decline remain largely elusive. This proposal will test the hypothesis that BBB breakdown initiates disease onset and progression in humans with genetically defined SVD (NOTCH3 mutation carriers suffering from cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy or CADASIL). The proposal will use a unique cohort of Chinese CADASIL patients already lined up for study inclusion at Xuanwu Hospital, Capital Medical University in Beijing. With cutting-edge BBB permeability imaging techniques at 3 and 7 Tesla, using dynamic contrast enhanced (DCE) MRI and diffusion-weighted arterial spin labeling (DW ASL), as well as other innovative biomarkers of SVD as part of the MarkVCID consortium (www.markvcid.org), we will systematically investigate the clinical, neuropsychological, and imaging changes during CADASIL progression. In 3 aims, we will first evaluate the repeatability and correlation between BBB permeability to Gadolinium-based contrast agent (GBCA) and water respectively in the cohort of Chinese CADASIL patients. Using a longitudinal study, we will then determine the initiating role of BBB breakdown using DCE MRI and DW ASL in the cohort of Chinese CADASIL patients to test the hypothesis that increased BBB permeability in NOTCH3 mutation carriers initiates disease onset and progression, such as cerebral blood flow (CBF) reductions, development of WM lesions and free water content, ischemic infracts and mircrohemorhages, and cognitive decline. We will further develop and evaluate a multiparametric MRI protocol for CADASIL patients including BBB permeability imaging at ultrahigh field of 7T. Leveraging a unique cohort of Chinese CADASIL patients, and applying cutting-edge imaging approaches at 3 and 7T, this US-China Biomedical Collaboration project will define the initiating role of BBB dysfunction in cerebral SVD, and will establish the BBB as a new key target for therapeutic interventions in CADASIL and by extension SVD. This project will also result in cutting-edge BBB permeability imaging protocols at 3 and 7T as early imaging markers of SVD.


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: 2024 ( Subtotal = $240,075 )
2024	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90089	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	1/11/2024	NON-COMPETING CONTINUATION	$222,749
2024	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90089	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	4/10/2024	NON-COMPETING CONTINUATION	$17,326
														Subtotal = $240,075

Issue Date FY: 2023 ( Subtotal = $247,500 )
2023	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	2/1/2023	NON-COMPETING CONTINUATION	$247,500
														Subtotal = $247,500

Issue Date FY: 2022 ( Subtotal = $247,500 )
2022	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	1/7/2022	NON-COMPETING CONTINUATION	$222,748
2022	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	3/28/2022	NON-COMPETING CONTINUATION	$24,752
														Subtotal = $247,500

Issue Date FY: 2021 ( Subtotal = $247,500 )
2021	2021	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	1/27/2021	NON-COMPETING CONTINUATION	$247,500
														Subtotal = $247,500

Issue Date FY: 2020 ( Subtotal = $247,500 )
2020	2020	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	1/17/2020	NEW	$247,500
														Subtotal = $247,500

Grand Total All Awards = $1,230,075

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BBB Permeability Imaging in CADASIL

Award Number: R01NS114382

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: 02/01/2020

PERIOD OF PERFORMANCE END DATE: 01/31/2025

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