# Development of a Multi-Modal MRI Methodology to Map Paravascular Clearance Linked to Astrocyte Dysfunction in Fetal-Onset Hydrocephalus

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $462,000

## Abstract

Fetal-onset hydrocephalus is the most frequent pediatric disease requiring surgical intervention, which can lead
to abnormal cortical development and life-long neurological deficits. An ongoing challenge to provide “non-sur-
gical treatment” of the fetal-onset hydrocephalus is to elucidate the underlying regulatory mechanism of glym-
phatic dysfunction. In particular, the functional dynamic interaction of astrocyte activation and paravascular clear-
ance in the hydrocephalus brain remains elusive. The goal of this proposal is to develop a multi-modal MRI
methodology to identify CSF dynamic abnormality and impaired paravascular clearance at pre/postnatal stages
and characterize the pathophysiological astrocyte function at the juvenile stage of fetal-onset hydrocephalus,
aiming to provide novel biomarkers with diagnostic, prognostic, and therapeutic value. We will implement a 3-
dimensional Modified-Driven-Equilibrium Fourier Transform (3D-MDEFT)-based Manganese-enhanced MRI
(MEMRI) method to estimate the Mn distribution and clearance dynamics in both parenchyma (i.e. paravascular
clearance) and ventricles (CSF flow dynamics) as markers of glymphatic circulation in pre/postnatal mice. Also,
we will apply the balanced steady-state free precession (bSSFP)-based single-vessel fMRI method to identify
the vessel-specific resting-state hemodynamic correlation changes in juvenile mice. The altered vascular hemo-
dynamics and paravascular clearance features of the hydrocephalic brain will be mapped in combination with
the GCaMP6-mediated astrocytic Ca2+ fiber optic recordings in both cortex and hippocampus. We will address
the proposal in two aims: 1). Identify CSF dynamic abnormality and impaired paravascular clearance in pre/post-
natal GFAP/TGF-β1 transgenic mice with fetal-onset hydrocephalus. We will develop MDEFT-based MEMRI to
map the distribution and clearance of Mn-enhanced CSF and parenchyma signals cross pre/postnatal stages of
the hydrocephalic mice. 2. Correlate the astrocyte-mediated vascular hemodynamics to the abnormal paravas-
cular clearance of the fetal-onset hydrocephalic brain. We will combine the concurrent single-vessel fMRI with
optical fiber-mediated astrocytic Ca2+ recording to elucidate the dynamic linkage of astrocytic dysfunction, im-
paired paravascular clearance, and pathological vascular hemodynamics in the hydrocephalic brain. Using novel
multi-modal MRI methods, we expect to identify specific markers for glymphatic dysfunction, which can be trans-
lated to guide and optimize treatments of glymphatic dysfunction of fetal-onset hydrocephalus.

## Key facts

- **NIH application ID:** 10370865
- **Project number:** 1R21NS121642-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Xin Yu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $462,000
- **Award type:** 1
- **Project period:** 2021-09-20 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10370865

## Citation

> US National Institutes of Health, RePORTER application 10370865, Development of a Multi-Modal MRI Methodology to Map Paravascular Clearance Linked to Astrocyte Dysfunction in Fetal-Onset Hydrocephalus (1R21NS121642-01A1). Retrieved via AI Analytics 2026-06-10 from https://api.ai-analytics.org/grant/nih/10370865. Licensed CC0.

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