# Non-invasive MRI mapping of BBB water exchange rate and permeability

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2024 · $691,074

## Abstract

Project Summary/Abstract
The blood-brain barrier (BBB) plays a crucial role in protecting the central nervous system (CNS)
from harmful substances such as plasma proteins and inorganic solutes. A non-invasive MRI
technique to detect subtle BBB dysfunction could be an extremely valuable tool for early diagnosis
of neurodegenerative disorders. Our team has developed a diffusion prepared pseudo-continuous
arterial spin labeling (OP-pCASL) technique for mapping BBB water exchange rate (kw), which
has been validated by preclinical studies and found to be associated with aging, small vascular
disease, APOE epsilon4 genotype, amyloid PET, and CSF Aβ-42 in cognitively normal subjects.
However, the OP-pCASL technique currently has low spatial resolution and cannot estimate the
permeability surface area product of water (PSw) due to a lack of venous compartment in its
modeling. Mapping both kw and PSw is significant because they assess different aspects of the
BBB and provide comprehensive information about its function. Changes in PSw can indicate a
combination of changes in capillary surface and permeability, making it a potential biomarker for
subtle BBB leakage across endothelial cells. In contrast, kw measures the exchange rate between
blood and tissue and can be more sensitive to transport mechanisms, e.g. AQP4 function, and
potentially linked to the glymphatic function. However, the exact neurophysiological mechanisms
of kw and PSw are still unclear. The proposed project aims to develop and optimize a highresolution
diffusion-weighted arterial spin labeling (OW-ASL) technique and mathematical models
to non-invasively quantify BBB kw and PSw simultaneously. The individual BBB kw and PSw
measurements will be evaluated for test-retest repeatability. The age-related changes of BBB
function and BBB dysfunction in cerebral small vessel disease (cSVO) will be investigated by
measuring kw and PSw in a cohort of healthy subjects across the lifespan of 18-90 years and
elderly subjects (age> 60 years) with cSVO from USC VCIO study. Finally, the mechanisms of
BBB water exchange will be studied in AQP4-knockout mice and in models of mannitol-induced
BBB disruption. The outcome of this project will be a cutting-edge OW-ASL pulse sequence and
post-processing pipeline that allows for high-resolution mapping of kw and PSw, with an
understanding of their neurophysiological mechanisms.

## Key facts

- **NIH application ID:** 10980043
- **Project number:** 1R01NS134712-01A1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Danny JJ WANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $691,074
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980043

## Citation

> US National Institutes of Health, RePORTER application 10980043, Non-invasive MRI mapping of BBB water exchange rate and permeability (1R01NS134712-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10980043. Licensed CC0.

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