IMAGING BRAIN-WIDE SUBARACHNOID AND PERIVASCULAR CEREBROSPINAL FLUID FLOW IN AGING AND ALZHEIMER'S DISEASE…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
Assistance award details
- Assistance award identifier
- ASST_NON_R00AG083056_075
- FAIN
- R00AG083056
- Recipient
- THE GENERAL HOSPITAL CORPORATION
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $492,817
- Period
- Aug 1, 2023 – Jul 31, 2028
- Fiscal year
- 2025
- Place of performance state
- MA
- Source file
- FY2025_All_Assistance_Full_20261006.zip
Description
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 CLEARANCEâSUBARACHNOID 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 OU