# Macromolecular Imaging of Gray and White Matter Pathology in Multiple Sclerosis

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $425,691

## Abstract

Abstract: Macromolecular Imaging of Gray and White Matter Pathology in Multiple Sclerosis
Multiple sclerosis (MS) is a complex inflammatory, demyelinating, neurodegenerative disease of
the central nervous system, highly variable in its symptoms, clinical course, and underlying
pathological changes in the brain. Conventional magnetic resonance imaging (cMRI) is
essential to diagnosis and management of MS but it lacks sufficient sensitivity and specificity to
MS pathology, correlates poorly with clinical disability and has limited prognostic value. In
particular, cMRI fails to detect most of the disease burden in cortical gray matter (GM), recently
recognized as a major site of pathology in MS, which is now understood to be a whole-brain (not
exclusively white matter) disease. More sensitive, specific, and reliable imaging biomarkers are
critically needed for earlier diagnosis and more accurate monitoring of disease progression and
therapy. The overarching aim of this proposal is to meet this need through development of
novel, clinically feasible, quantitative MRI methods based on the phenomenon of magnetization
transfer (MT), a powerful yet underdeveloped method to quantify macromolecular changes in
tissue.
Despite a large volume of published work to date, MT imaging in its present form still lacks
sufficient sensitivity, specificity, and reliability to meet the needs of MS management and clinical
research. So-called quantitative MT imaging (qMTI) was developed to correct these
deficiencies. The principal qMTI parameter, macromolecular pool fraction, has been shown to
reflect myelin content and, when measured in cortical GM, predict clinical disability more
accurately than any other imaging measure studied. These results could herald a paradigm shift
in the assessment of MS as whole-brain disease; however, several obstacles still impede the
application of qMTI in clinical and clinical research settings. The first aim of this proposal will be
to develop the next-generation qMTI methodology immune to cerebrospinal fluid partial volume
effects and corrected for factors affecting tissue water content (edema/inflammation/gliosis), all
optimized for imaging with a minimum number of MRI acquisitions. The second aim will be to
accelerate the constituent image acquisitions for this protocol, yielding a fast, robust, high-
resolution implementation of qMTI for clinical settings. Finally, the third aim will be to validate
the clinical utility of the new qMTI biomarkers in a cross-sectional cohort of MS patients and
age-matched controls. Specifically, we will determine whether they predict cognitive impairment
more accurately than existing imaging methods.

## Key facts

- **NIH application ID:** 10232072
- **Project number:** 5R01EB027087-04
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Alexey Samsonov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $425,691
- **Award type:** 5
- **Project period:** 2018-09-30 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10232072

## Citation

> US National Institutes of Health, RePORTER application 10232072, Macromolecular Imaging of Gray and White Matter Pathology in Multiple Sclerosis (5R01EB027087-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10232072. Licensed CC0.

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