# Mesoscopic Biomarkers of Neurodegeneration and Inflammation with Diffusion MRI

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $680,902

## Abstract

PROJECT SUMMARY
Diseases of the central nervous system (CNS) are a significant public health and economic problem, affecting
one in three Americans at some point in life, and costing over $500 billion per year. Pathologically, the white
matter (WM) is compromised in CNS disorders by neuro-inflammatory processes (gliosis, astrocytosis,
macrophage infiltration), acute axonal beading, and neurodegenerative processes (demyelination, axonal
degeneration and loss). While axonal degeneration results in irreversible disability, the roles of different
inflammatory processes, and their interplay with neurodegeneration, are unknown, mainly due to the lack of
biomarkers that parse these concurrent processes in vivo in humans.
Our main objective is to distinguish and quantify neurodegenerative and inflammatory processes in WM with
MRI, and evaluate them as prognostic markers for Multiple Sclerosis (MS), a chronic inflammatory and
neurodegenerative disorder.
In Aim 1, we will develop a fast T2-weighted dMRI sequence unifying our TE-dependent Diffusion Imaging
(TEdDI) technique with free gradient wave forms reducing acquisition time to within 15 minutes, and employ
Cramer-Rao lower bound minimization to find an optimal protocol for estimating intra- and extra-axonal water
fractions, diffusion coefficients and relaxation times, which are the proposed markers of neurodegeneration
and inflammation. We will then test the protocol's accuracy and reproducibility on phantoms and volunteers.
In Aim 2, we will use our protocol to track neurodegeneration and inflammation both cross-sectionally and
longitudinally on MS patients at different stages in the disease, and identify specific changes of all parameters
with increasing disease severity. We expect that our neurodegeneration-related parameters will be more
sensitive than lesion load and volumetrics in tracking disability. Furthermore, we will for the first time assess
changes in compartmental diffusivities and relaxation times and relate them to MS disease progression.
In Aim 3, we will develop a framework of realistic Monte Carlo random walk simulations in WM geometries
reconstructed from 3d electron microscopy. Ab initio, we will quantitatively explore the effect of gliosis,
beading, demyelination and axonal loss in normal-appearing WM on diffusion and WM microstructure markers.
Overall, the project will yield novel non-invasive clinically feasible diffusion MRI markers sensitive and specific
to diffuse neurodegeneration and inflammatory processes, that could help better understand MS disease
progression and open new avenues for effective management of patients and therapy development. The
developed MRI pipeline for estimating WM microstructure markers will be straightforwardly extendable beyond
MS, to help understand and quantify neurodegeneration and inflammation in other neurological diseases.

## Key facts

- **NIH application ID:** 10022344
- **Project number:** 5R01NS088040-07
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Els Fieremans
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $680,902
- **Award type:** 5
- **Project period:** 2014-09-30 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10022344

## Citation

> US National Institutes of Health, RePORTER application 10022344, Mesoscopic Biomarkers of Neurodegeneration and Inflammation with Diffusion MRI (5R01NS088040-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10022344. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*