# Interaction between glymphatic and vascular systems for waste clearance in brain - Administrative Supplement

> **NIH NIH R01** · HENRY FORD HEALTH SYSTEM · 2021 · $200,165

## Abstract

ABSTRACT
The objective of this current proposal is to investigate aging induced changes of brain waste clearance in the
meningeal lymphatic and glymphatic systems using superparamagnetic iron oxide (SPIO)-enhanced
susceptibility weighted imaging (SWI, SPIO-SWI) and fluorescent imaging. Emerging data indicate that the
glymphatic system mediates the cerebrospinal fluid (CSF)-interstitial (ISF) exchange and solute clearance from
the brain parenchyma and plays an important role in neurological diseases1-6. However, despite many milestone
achievements, conclusive findings on the solute efflux pathways are relatively limited. In our funded RO1
(NS108463), we investigate the effects of diabetes on glymphatic and vascular system cerebral waste clearance.
The recently discovered meningeal lymphatics has also been shown to be important for cerebral waste
clearance. However, the interaction between the meningeal lymphatic and glymphatic systems on cerebral waste
clearance has not been investigated.
 The paucity of research into the efflux pathways may be attributed, in part, to the technical difficulties of
performing minimally invasive in vivo, ultra-high detection sensitivity measurements of influx and efflux pathways,
and whole brain imaging. Although MRI can overcome the weak points of two-photon imaging (TPI), to provide
non-invasive whole brain in vivo imaging of the glymphatic system, conventional MRI sensitivity is insufficient to
investigate microvessels of the meningeal lymphatic and glymphatic systems. During the past funded period we
have successfully optimized and validated highly sensitive MRI microvessel measurement. We have identified
an optimal TE-dose index to greatly improve visualization of sub-voxel vessels (detecting ~10µm diameter
microvessels), and have demonstrated that the parenchymal venous system also plays an important role in
cerebral waste clearance7-9. The recently discovered meningeal lymphatics has been proposed to be an
important efflux pathway for cerebral waste clearance, and the decrease in cerebral waste clearance mediated
by a dysfunctional relationship between the meningeal lymphatics and the glymphatic system during, serves as
an aggravating factor for Alzheimer’s disease pathology and age-associated cognitive decline10, 11. However,
several critical issues for this important topic have not been addressed. Based on our novel preliminary data,
and published studies, we hypothesize that the newly optimized SPIO-SWI method significantly increases
detection sensitivity of microvessels in both the meningeal lymphatic and glymphatic systems, and that the efflux
pathways of waste clearance can be identified and investigated using this optimized SPIO-SWI method. To test
these hypotheses, we will investigate the effects of aging on the interaction between the meningeal lymphatic
and glymphatic systems during waste clearance using the optimized USPIO-SWI method and fluorescent
imaging. Data generated from this current proposa...

## Key facts

- **NIH application ID:** 10399708
- **Project number:** 3R01NS108463-04S1
- **Recipient organization:** HENRY FORD HEALTH SYSTEM
- **Principal Investigator:** JIANI HU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $200,165
- **Award type:** 3
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10399708

## Citation

> US National Institutes of Health, RePORTER application 10399708, Interaction between glymphatic and vascular systems for waste clearance in brain - Administrative Supplement (3R01NS108463-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10399708. Licensed CC0.

---

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