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Imaging brain-wide subarachnoid and perivascular cerebrospinal fluid flow in aging and Alzheimer's disease

Award Number: K99AG083056
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 08/01/2023
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Imaging brain-wide subarachnoid and perivascular cerebrospinal fluid flow in aging and Alzheimer's disease - PROJECT SUMMARY / ABSTRACT The impaired clearance of neuropathological proteins has been increasingly recognized in Alzheimer's disease (AD). Cerebrospinal fluid (CSF) flow plays an essential role in the waste clearance process of the brain, and disruptions of CSF flow are implicated in AD. However, most of the studies on CSF clearance were conducted in animals, and the CSF flow dynamics and clearance pathways in the human brain remain poorly understood. Most of the human studies on brain CSF flow are only able to investigate flow dynamics in ventricles or in the aqueduct so far due to the lack of sufficient imaging tools, and little is known about CSF flow in the key regions for clearance—subarachnoid space (SAS) and perivascular space (PVS). This poses a major barrier to studying brain-wide CSF flow dynamics and clearance pathways as well as their correlation with aging and AD pathology, which are essential steps toward understanding the clearance process of toxic proteins in AD. To overcome this barrier, the goal of this proposal is to develop the first whole-brain MR CSF flowmetry that extends the imaging area from ventricles to previously inaccessible SAS and PVS, and apply it to investigate the alteration of brain-wide CSF flow in aging and AD, and its correlation with neuropathological protein deposition. The flowmetry technique will provide unparalleled sensitivity, specificity, efficiency, and spatiotemporal resolution to map SAS/PVS CSF flow in the human brain. Using this tool, we will answer key questions about brain-wide SAS/PVS flow dynamics and pathways as well as their driving factors in the human brain. We will then study how CSF flow dynamics change with healthy aging and how they are disrupted in AD patients, especially how flow stagnation correlates with amyloid-beta and tau deposition using MR flowmetry combined with PET imaging. The outcome of this study will significantly advance our knowledge of brain clearance in aging and AD, and lay the foundation for future investigation of CSF-flow-based imaging biomarkers and therapeutic interventions for AD to improve clinical outcomes. The candidate has in-depth training in neuroimaging, MR physics and state-of-the-art MR methodology, and signal processing. He is seeking additional training in Alzheimer's disease, translational research skills, and multi-model imaging analysis from this grant mechanism, to achieve his long-term career goal to become an independent investigator in neuroimaging of neurodegenerative diseases, and establish research programs that develop innovative neuroimaging technologies, apply them to advance our understanding of aging and neurodegeneration, and translate these technologies to facilitate the discovery of non-invasive imaging biomarkers and aid in the development of therapeutic interventions of Alzheimer's disease and related dementias. He will work with a multi-disciplinary team of mentors and collaborators who are world-renowned experts in their respective fields, and leverage the exceptional resources at Massachusetts General Hospital to achieve his scientific and career development goals.


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: 2026 ( Subtotal = $0 )
2026	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Aging Research	000	2	12/9/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $133,920 )
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Aging Research	000	2	7/31/2024	NON-COMPETING CONTINUATION	$133,920
														Subtotal = $133,920

Issue Date FY: 2023 ( Subtotal = $133,920 )
2023	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Aging Research	000	1	7/18/2023	NEW	$133,920
														Subtotal = $133,920

Grand Total All Awards = $267,840

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Imaging brain-wide subarachnoid and perivascular cerebrospinal fluid flow in aging and Alzheimer's disease

Award Number: K99AG083056

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 08/01/2023

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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