# MR metabolic Imaging of Multiple Sclerosis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $346,719

## Abstract

ABSTRACT
 Multiple sclerosis (MS) is a multifaceted neurological disease and one of the most common causes of
disability in young adults. The major hallmark of MS is an uncontrolled immune response that drives
demyelination, resulting in continuously worsening cognitive impairments, and eventually leading to death.
 Upon clinical diagnosis of MS, numerous clinical evaluations and MR Imaging (MRI) sessions are required
to assess symptoms and/or presence of lesions. Even then, prediction of outcome and choice of treatment
remain a challenge for each patient. Given the role of inflammation in MS, an imaging method that could detect
immune response could improve patient management and subsequent individualized therapeutic approaches.
 In MS lesions, mononuclear phagocytes (MPs, macrophages/microglia) are the most abundant immune
cells, and drive demyelination and cell death. Interestingly, to sustain high proliferation rates, these MPs have
switched from quiescent to pro-inflammatory (M1-polarized) activated state and show increased lactate
production linked to increased pyruvate dehydrogenase kinase 1 (PDK1). During remissions or in response to
therapies, activated MPs switch to a neuroprotective (M2) phenotype and participate in remyelination.
Remarkably, M2 MPs present the unique metabolic feature of excreting high levels of arginase, an enzyme
that inhibits T cells function through depletion of the arginine pool.
 The goal of this study is to test the hypothesis that MPs activation and M1/M2 status can be detected in
MS lesions in vivo using hyperpolarized 13C MR Spectroscopic Imaging (HP 13C MRSI) and that such
metabolic imaging can improve evaluation of MS progression and treatment response. Our Aims are:
 Aim 1. Validate 13C MRSI of HP pyruvate as an imaging method to monitor activated MPs in MS
lesions in vivo. 13C MRSI of HP [1-13C] pyruvate, the most established and clinically translatable probe, will be
used to detect PDK1+/activated MPs through increased HP lactate production in two well-characterized
preclinical MS models. Comparison with established MRI methods will be performed to assess the sensitivity,
specificity and diagnostic accuracy of the method, and its improved potential to monitor disease progression.
 Aim 2. Detect neuroprotective M2 MPs in MS lesions using in vivo 13C MRSI of hyperpolarized
arginine. We will optimize 13C MRSI of HP guanidino-13C-arginine, the substrate of arginase, to non-invasively
and specifically detect arginase+/M2 MPs in vivo through detection of HP urea in preclinical MS models.
Comparison to MRI/S will also be performed to assess the improved diagnostic accuracy of this approach.
 Aim 3. Evaluate in vivo MR metabolic imaging to monitor response to therapies. We will combine 13C
MRSI of HP [1-13C] pyruvate and HP guanidino-13C-arginine and use this multiprobe metabolic imaging
approach to monitor response to clinically relevant therapies in two preclinical MS models. Comparison to
MRI/S methods will ...

## Key facts

- **NIH application ID:** 10162675
- **Project number:** 5R01NS102156-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Myriam Marianne Chaumeil
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $346,719
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10162675

## Citation

> US National Institutes of Health, RePORTER application 10162675, MR metabolic Imaging of Multiple Sclerosis (5R01NS102156-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10162675. Licensed CC0.

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