# Validation of Diffusion Basis Spectrum Imaging of Neuroinflammation in Schizophrenia

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2024 · $194,375

## Abstract

PROJECT SUMMARY
Schizophrenia (SCZ) is a heterogeneous brain disorder typically characterized by delusions, hallucinations, and
functional decline, with a typical first onset in late adolescence and early adulthood. Genetic, neuropathological,
and neuroimaging studies have suggested a role of neuroinflammation in the etiology of SCZ, which is evident
early in the course of illness. This suggests neuroinflammation may represent a SCZ risk marker and therefore
facilitate early recognition and future drug development to improve outcomes. In vivo imaging methods for
estimating neuroinflammation have been limited by radiation exposure, specificity, and cost. Our proposal aims
to validate a novel non-invasive, new magnetic resonance imaging (MRI) technique called Diffusion Basis
Spectrum Imaging (DBSI) to identify neuroinflammation in SCZ. DBSI can simultaneously detect and quantify
neuroinflammation (increased cellularity) and white matter alterations (axonal injury/loss and demyelination) and
has been previously validated in multiple sclerosis and Alzheimer's disease, but not in SCZ. We propose to test
the overarching hypothesis that DBSI will identify neuroinflammation in histological samples from SCZ patients.
To achieve this objective, we will obtain postmortem brain samples of 18–30-year-old SCZ patients and matched
controls (n=20) from the NIH Neurobiobank and investigate the relationship of the DBSI cellularity subcomponent
with tissue reactivity for the microglial marker, CD163, and the complement marker, C4 (Aim 1). We hypothesize
a strong linear relationship between DBSI cellularity and selected gray and white matter regions. In addition, we
will use DBSI in vivo to characterize the brains of 18–30-year-old SCZ patients and controls (n=30) and identify
group differences in DBSI subcomponents (Aim 2). We hypothesize greater DBSI cellularity in SCZ brains
compared to controls. In completing this work, we expect to identify non-invasive neuroinflammation and white
matter integrity markers for SCZ. In the long term, this information would be used to improve the identification of
those at risk for developing psychosis and facilitate the testing of new treatments.

## Key facts

- **NIH application ID:** 10745333
- **Project number:** 5R21MH131962-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** DANIEL MAMAH
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $194,375
- **Award type:** 5
- **Project period:** 2022-12-01 → 2025-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10745333

## Citation

> US National Institutes of Health, RePORTER application 10745333, Validation of Diffusion Basis Spectrum Imaging of Neuroinflammation in Schizophrenia (5R21MH131962-02). Retrieved via AI Analytics 2026-05-30 from https://api.ai-analytics.org/grant/nih/10745333. Licensed CC0.

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