# Fast Diffusion MRI assay for Studying Neurodegeneration in Alzheimer’s Disease

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2022 · $344,900

## Abstract

Project Summary:
Neurodegenerative disorders (NDDs) are a significant public health and economic problem and are the leading
cause of disability worldwide. Understanding the specific degenerative processes that are actively progressing
over the course of the illness is crucial for developing targeted drugs therapies and deciding treatment options.
Additionally, understanding the structural connectivity changes to tease apart the specific circuitry affected is
crucial in developing circuit specific non-invasive brain stimulation therapies. The myelin model of
neurodegeneration (ND) is now gaining interest in several neurodegenerative disorders. Based on this model,
many of the degenerative processes implicated in the early stages of neurodegeneration are reversable, which
offer hope for interventions to slow down or reverse the course. Hence, finding early interventional targets with
high specificity to the degenerative processes involved in the ND cascade, and quantifying the response to
targeted interventions are critically important to enable studies of NDDs in humans. Diffusion-based MRI
assays can provide microstructural measures that are highly sensitive to (i) the neurodegenerative processes
and (ii) connectivity changes. Coupled with detailed biophysical models that link the diffusion measurements to
the physical properties of the neuronal sub-compartments, biomarkers that can differentiate the degenerative
processes can now be derived. The parent grant aims to develop a novel diffusion MRI assay to generate
dMRI measurements that enable the biophysical modeling to study the NDD cascade.
In this administrative supplement, we propose to extend Specific Aim 1 of the parent grant to include
experiments related to Alzheimer's disease (AD) and its related dementias and to quantify the stage-specific
biomarkers of neurodegeneration. The proposed development will make use of SNR-efficient 3D acquisitions
utilizing multi-band RF pulses. Coupled with time-efficient sparse k-q sampling, the 3D encoding will span over
multiple b-shells. To enable the biomarker studies, an extensive q-space sampling scheme, that will cover 4 b-
shells to provide 120 samples at high SNR, is developed which enables the utilization of advanced biophysical
modeling approaches. Further, we will validate the biomarkers derived from the dMRI assay on a cohort of AD
to study the full course of neurodegenerative cascade.

## Key facts

- **NIH application ID:** 10498507
- **Project number:** 3R01EB031169-02S1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Merry Mani
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $344,900
- **Award type:** 3
- **Project period:** 2021-06-15 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10498507

## Citation

> US National Institutes of Health, RePORTER application 10498507, Fast Diffusion MRI assay for Studying Neurodegeneration in Alzheimer’s Disease (3R01EB031169-02S1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10498507. Licensed CC0.

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