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

> **NIH NIH K99** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $133,920

## Abstract

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
r...

## Key facts

- **NIH application ID:** 10890172
- **Project number:** 5K99AG083056-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Zijing Dong
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $133,920
- **Award type:** 5
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10890172

## Citation

> US National Institutes of Health, RePORTER application 10890172, Imaging brain-wide subarachnoid and perivascular cerebrospinal fluid flow in aging and Alzheimer's disease (5K99AG083056-02). Retrieved via AI Analytics 2026-07-20 from https://api.ai-analytics.org/grant/nih/10890172. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*