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

> **NIH NIH R01** · HENRY FORD HEALTH SYSTEM · 2022 · $559,486

## Abstract

ABSTRACT
The objective of this application is to first develop and validate microvessel measurement for the entire brain to
enhance detection sensitivity of microvessels by ten-fold using superparamagnetic iron oxide (SPIO) enhanced
susceptibility weighted imaging (SWI, SPIO-SWI) and then to investigate the interaction between glymphatic and
vascular systems for waste clearance in the diabetic brain. Emerging data indicate that the glymphatic system
in the brain mediates the cerebrospinal fluid (CSF)-interstitial (ISF) exchange and solute clearance from the brain
parenchyma and plays an important role in neurological diseases1-6. Despite many milestone achievements,
conclusive findings on the solute efflux pathways are relatively limited. Consequently, the interaction between
vascular and glymphatic systems on waste clearance, especially with neurological diseases, is unclear.
 The paucity of research into the efflux pathway may be attributed in part to technical difficulties, such as the
challenging need to perform minimally invasive in-vivo, ultra-high detection sensitivity for tube-shaped influx and
efflux pathways, and whole brain imaging. Although MRI can overcome the weak points of two-photon confocal
microscopy to provide non-invasive whole brain in-vivo imaging of the glymphatic system, conventional MRI
sensitivity is insufficient for the required spatial resolution for investigating microvessels of glymphatic and
vascular systems. We have developed highly sensitive MRI methods (Fig. 1) which significantly improve the
detection sensitivity of small vessels by using the combination of high susceptibility of MRI agents with blooming
effects7-9. The new methods provide excellent tools for investigating the efflux pathways of waste clearance
under normal and pathophysiological conditions. Three efflux routes have been recently proposed and solutes
in the brain could reach the lymphatic network by the olfactory bulb across the ethmoid plate10, 11 or by functioning
conventional lymphatic vasculature in the meninges12. We found that tracer concentration in the venous system
significantly increased with diabetes (Fig. 9), thus adding a new route for brain waste clearance. Based on our
novel preliminary data and published studies by others, we hypothesize that, the newly developed SPIO-SWI
technique significantly increases detecting sensitivity of microvessels in both vascular and glymphatic systems,
and the efflux pathways of waste clearance with and without diabetes can be identified and investigated using
this optimized SPIO-SWI method. To test these hypotheses, we will first (Aim 1) further develop, optimize and
validate SPIO-SWI techniques to enhance the detection sensitivity for both vascular and glymphatic
microvessels. We will perform computer simulation, optimize SWI technique and experimental conditions in
animal studies and then validate USPIO-SWI technique by LSCM measurements. We will then (Aim 2)
investigate the interaction between v...

## Key facts

- **NIH application ID:** 10409674
- **Project number:** 5R01NS108463-05
- **Recipient organization:** HENRY FORD HEALTH SYSTEM
- **Principal Investigator:** JIANI HU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $559,486
- **Award type:** 5
- **Project period:** 2018-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10409674

## Citation

> US National Institutes of Health, RePORTER application 10409674, Interaction between glymphatic and vascular systems for waste clearance in brain (5R01NS108463-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10409674. Licensed CC0.

---

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