# Quantitative Endogenous MRI Imaging of Neuroinflammation in AD

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $723,436

## Abstract

PROJECT SUMMARY/ABSTRACT
Neuroinflammation plays a central role in the pathogenesis of Alzheimer’s disease (AD) and links strongly with
AD’s neuropathological hallmarks, including amyloid plaques and neurofibrillary tangles. While there have
been tremendous strides over the last decade in the development of novel cerebrospinal fluid, blood-based
assays, positron emission tomography (PET), and magnetic resonance imaging (MRI) techniques, there still is
a desperate need for a clinical imaging modality that can reliably image and quantify neuroinflammation in the
aging brain and facilitate the identification of the key pathological players in different stages of AD. To address
this unmet need and response to FOA “PAR-21-038”, we propose a new research direction to develop and
establish a brand-new diffusion MRI (dMRI) technique, Diffusion Dictionary Imaging (DDI), as a safe,
specific endogenous, and economical solution for the neuroinflammation imaging in AD. By tracking the
random walk of water molecules using FDA-approved diffusion MRI sequence and compressed sensing
technique, DDI measures and specifically extracts the microstructural changes associated with the activation
and infiltration of the microglia and astrocyte in AD. Moreover, the previously collected dMRI data can be
retrospectively analyzed with this new technique. Therefore, we are in a unique position to cost-effectively
develop DDI by leveraging the longitudinal data-rich studies from the Knight Alzheimer’s Disease Research
Center (ADRC) at Washington University (>800 Sporadic AD participants) and the multi-site international
Dominantly Inherited Alzheimer Network (DIAN) observational study (>500 autosomal-dominant AD [ADAD]
participants). In this project, we will develop the DDI technique and evaluate its capability of imaging
neuroinflammation in the postmortem AD brains (Aim 1). We will examine the associations between the DDI
neuroinflammation index and CSF and plasma inflammation biomarkers (YKL-40, sTREM2, and GFAP) in the
Knight ADRC and DIAN cohorts (Aim 2). We will also cross-sectionally and longitudinally quantify the
neuroinflammation using DDI in the Knight ADRC and DIAN cohorts and examine its connections with amyloid
deposition and tauopathy measured by PET tracers and clinical outcomes (cognitive and progression) (Aim 3).
The successful development of a quantitative endogenous DDI imaging biomarker of neuroinflammation will
represent an important technological leap forward. The integration of DDI neuroinflammation biomarker into the
DIAN and other clinical trial studies will provide clinically feasible neuroimaging surrogates that can significantly
improve our understanding of the role of neuroinflammation in AD pathogenesis.

## Key facts

- **NIH application ID:** 10782472
- **Project number:** 5R01AG074909-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** QING WANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $723,436
- **Award type:** 5
- **Project period:** 2022-04-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10782472

## Citation

> US National Institutes of Health, RePORTER application 10782472, Quantitative Endogenous MRI Imaging of Neuroinflammation in AD (5R01AG074909-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10782472. Licensed CC0.

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