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Investigating Enlarged Perivascular Spaces as a Neuroimaging Biomarker of Cerebral Small Vessel Disease

Award Number: F30AG079506
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 05/10/2023
PERIOD OF PERFORMANCE END DATE: 11/09/2025

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Investigating Enlarged Perivascular Spaces as a Neuroimaging Biomarker of Cerebral Small Vessel Disease - ABSTRACT Cerebral small vessel disease (cSVD) is an important risk factor that may arise years before the onset of vascular contributions to cognitive impairment and dementia (VCID). cSVD is characterized by in-vivo neuroimaging biomarkers including enlarged perivascular spaces (ePVS). PVS are the site of interchange between interstitial fluid and cerebrospinal fluid which is believed to play a role in the removal of brain waste. Reduced clearance may lead to enlargement of the PVS and subsequent accumulation of toxic solutes characteristic of neurodegeneration. Given their presence in brain regions that support cognition, we hypothesize that quantitative, cross-sectional ePVS counts in cognitively normal older adults could serve as an early biomarker of VCID. Specifically, we anticipate ePVS will predict cognitive dysfunction and increased white matter lesion burden after three years. We will test this hypothesis in a cohort of 121 cognitively normal older adults ranging in age from 60-86 at baseline. Participants are scanned on a 3T Siemens Prisma magnetic resonance imaging scanner with a 64-channel head coil. ePVS are manually counted by an experienced rater blinded to participant demographics following consensus guidelines using T1 MPRAGE, T2 FLAIR, and Quantitative Susceptibility Mapping images. All ePVS are counted in a single, axial slice of four brain regions with high ePVS burden including the centrum semiovale (CS ePVS), basal ganglia (BG ePVS), hippocampus, and midbrain. Aim 1 will test the hypothesis that CS ePVS predict longitudinal changes in executive function, a specific cognitive domain affected in VCID. Our preliminary data using the same cohort include a negative relationship between CS ePVS and baseline Montreal Cognitive Assessment (MoCA) score, a standardized screening tool of global cognition. Aim 2 will test the hypothesis that baseline CS ePVS burden predicts increased deep white matter hyperintensity (WMH) volume in the centrum semiovale after three years. This expands on preliminary findings that CS ePVS are positively related to whole brain WMH volume, a marker of advanced cSVD. In Aim 3, regional cerebrovascular reactivity (CVR), a measure of microvascular dysfunction, will be analyzed using a novel BOLD- fMRI testing paradigm, as a potential mechanistic contributor of ePVS. The cross-sectional relationship between BG ePVS and basal ganglia CVR will be analyzed to capitalize on our preliminary data which show a negative relationship between BG ePVS and global CVR. We will further test an alternative hypothesis that the cerebrospinal fluid amyloid-beta 42/40 ratio, a biomarker of amyloid burden, is more closely associated with ePVS than CVR. These experiments will be carried out at the University of Kentucky Magnetic Resonance and Imaging Center and the Sanders-Brown Center on Aging, under the direction of an expert team of scientist and clinician mentors. This F30 predoctoral fellowship will provide the requisite experience, training, and knowledge to aid the trainee’s transition into the next step of his career as a scientist-neuroradiologist in the field of neuroscience of aging measuring similar endpoints using basic and translational neuroimaging techniques.


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: 2027 ( Subtotal = -$10,460 )
2027	2025	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Aging Research	000	3	10/27/2026	NON-COMPETING CONTINUATION	-$10,460
														Subtotal = -$10,460

Issue Date FY: 2025 ( Subtotal = $40,769 )
2025	2025	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Aging Research	000	3	4/24/2025	NON-COMPETING CONTINUATION	$40,487
2025	2025	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Aging Research	001	3	6/23/2025	NON-COMPETING CONTINUATION	$282
														Subtotal = $40,769

Issue Date FY: 2024 ( Subtotal = $56,974 )
2024	2024	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE	LEXINGTON	KY	40526	FAYETTE	USA	Aging Research	000	2	6/3/2024	NON-COMPETING CONTINUATION	$56,974
														Subtotal = $56,974

Issue Date FY: 2023 ( Subtotal = $42,262 )
2023	2023	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Aging Research	000	1	4/18/2023	NEW	$42,262
2023	2023	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Aging Research	001	1	4/18/2023	NEW	$0
														Subtotal = $42,262

Grand Total All Awards = $129,545

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Investigating Enlarged Perivascular Spaces as a Neuroimaging Biomarker of Cerebral Small Vessel Disease

Award Number: F30AG079506

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 05/10/2023

PERIOD OF PERFORMANCE END DATE: 11/09/2025

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