# Identifying mechanisms of tissue injury in MS lesions: a multi-modality imaging approach

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $420,110

## Abstract

Project Summary/Abstract
The overall goal of this proposal is to leverage the distinct advantages of different imaging modalities (PET and
MRI) to facilitate the testing of therapeutic strategies aimed at limiting cytotoxic damage and oxidative stress
within MS lesions for the promotion of myelin recovery and reduction of subsequent neurodegeneration.
 Mechanisms leading to tissue injury in MS are poorly understood, however sources of oxidative injury, such as
the innate immune response and iron release, are felt to contribute to myelin damage, limited myelin repair and
eventual axonal instability. Intervention with treatments targeting CNS pathways for immune modulation and
reduction of oxidative damage requires validation of timing and extent of damage; gaining this knowledge
provides the potential to intervene and prevent clinical disability. Our preliminary data demonstrates that PET
PK11195, a measure of m/M activation, is high at the time of gadolinium (Gd) enhancement in acute MS
lesions and quickly decreases in the following months, whereas lesion magnetic susceptibility, as measured by
quantitative susceptibility mapping (QSM) and is sensitive to iron, significantly increases in the months after
resolution of Gd-enhancement. Accordingly, this proposed research is to further describe these biological
mechanisms in early MS lesions and confirm our hypothesis that acute lesions with high innate immune activity
and high iron content would result in severe demyelination. We propose to test this hypothesis through our first
aim. Aim 1: Lesion iron mapping and a higher specificity PET ligand (DPA713) will be applied to a longitudinal
study of acute MS lesions and will define the relationship of iron release and m/M activation as well as
determine their association with subsequent lesion myelin content, as measured by MRI myelin water content
(MWC) imaging. We then hypothesize that residual lesion iron and myelin loss within chronic MS lesions will
lead to subsequent neuronal degeneration. We propose to test this hypothesis in our second aim. Aim 2: To
apply MWC/QSM to a well-defined cohort of MS patients for which we will measure the association of residual
iron and myelin loss within chronic MS lesions on subsequent global neuronal loss and clinical disability. The
overall goal of this proposal is to leverage the distinct advantages of different imaging modalities to facilitate
the use of MRI to identify patients that would benefit from a therapeutic intervention targeting the reduction in
CNS inflammation for the promotion of myelin recovery and reduction of disability.

## Key facts

- **NIH application ID:** 10251158
- **Project number:** 5R01NS104283-04
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Susan A Gauthier
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $420,110
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10251158

## Citation

> US National Institutes of Health, RePORTER application 10251158, Identifying mechanisms of tissue injury in MS lesions: a multi-modality imaging approach (5R01NS104283-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10251158. Licensed CC0.

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