# MR Metabolic Imaging of Multiple Sclerosis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $626,409

## Abstract

ABSTRACT
 For people living with multiple sclerosis (MS), numerous clinical and Magnetic Resonance Imaging (MRI)
sessions are needed to assess symptoms and/or presence of lesions. Even then, outcome prediction and
treatment choice are challenging. To realize the full potential of personalized medicine, specific biomarkers
reflecting function (e.g. inflammation, redox) are needed for comprehensive characterization and phenotyping.
 Over the initially funded 5-year period of this grant, we have firmly established that hyperpolarized (HP) 13C
MR Spectroscopic Imaging (MRSI) is a highly valuable neuroimaging method for assessment of MS lesions. We
were the first to show that 13C MRSI of HP [1-13C]pyruvate can detect increased HP lactate-to-pyruvate, linked
to proinflammatory microglia/macrophages (MPs) in a MS mouse model, a finding further confirmed in other
models. We also demonstrated that HP 13C MR could monitor early response to immunomodulatory therapies,
e.g. dimethylfumarate (DMF). Additionally, we showed that, as MPs phenotype is linked to levels of Reactive
Oxygen Species (ROS), HP [1-13C]dehydroxyascorbic acid (DHA), a redox-sensing HP probe, could differentiate
between M1 and M2 MPs, thus non-invasively assessing these orthogonal processes.
 In this renewal, we will build upon the successes of the first funded period and 1/develop improved HP 13C
metabolic imaging approaches to assess neuroinflammation and oxidative stress in MS and 2/conduct the first
human study applying HP 13C metabolic imaging to monitor therapy response in people living with MS.
 Specific Aim 1. Provide a comprehensive picture of metabolic impairment in MS using HP [1-
13C]pyruvate. 13C MRSI of HP [1-13C]pyruvate will be optimized at clinical field strength to simultaneously detect
oxidative and glycolytic metabolism through assessment of bicarbonate and lactate kinetics, respectively, in two
preclinical MS models at 3 Tesla. Spatial genomics, immunostainings and biochemical assays will be performed
on paired ex vivo samples to investigate the underlying mechanisms driving the HP readouts.
 Specific Aim 2. Differentiate orthogonal neuroinflammatory processes using HP g-Glutamyl-[1-
13C]Glycine. We will investigate the potential of g-Glu-[1-13C]Gly to assess oxidative stress as a read-out of
M1/M2 status in two MS models. To do so, 13C MRSI of HP g-Glu-[1-13C]Gly will be optimized to measure GGT
activity in vivo through detection of HP [1-13C]Glycine in preclinical MS models at 3 Tesla. Ex vivo analysis of
tissue samples will be performed as in Aim 1 to investigate the underlying mechanisms driving the HP readouts.
 Specific Aim 3. Perform the first study of MS patients using HP [1-13C]pyruvate: 3A. We will perform a
pilot study on 8 RRMS patients naïve to disease modifying therapies (DMTs), to optimize HP [1-13C] pyruvate
MRI parameters for improved resolution at 3 Tesla. 3B. We will then image 32 RRMS patients naïve to DMTs
using parameters defined in 3A, at baselin...

## Key facts

- **NIH application ID:** 10885196
- **Project number:** 5R01NS102156-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Jeremy William Gordon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $626,409
- **Award type:** 5
- **Project period:** 2017-09-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10885196

## Citation

> US National Institutes of Health, RePORTER application 10885196, MR Metabolic Imaging of Multiple Sclerosis (5R01NS102156-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10885196. Licensed CC0.

---

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