# Magnetic resonance imaging of human post-mortem tissues with a clinical diagnosis of multiple sclerosis using inhomogeneous magnetization transfer

> **NIH NIH R21** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2020 · $218,750

## Abstract

PROJECT SUMMARY/ABSTRACT
The National Multiple Sclerosis (MS) Society estimates that 1 million people are living with MS in the United
States. The importance of magnetic resonance imaging (MRI) in diagnosis of the demyelinating neurological
disease MS is evident from the McDonald Criteria guidelines. However the use of MRI in diagnosis of MS is
often qualitative and analysis of images from the central nervous system is subjective. This application is
dedicated to development of a robust, quantitative MRI technique, known as inhomogeneous
magnetization transfer (ihMT), for future use in MS diagnosis. The ihMT MRI technique demonstrates
myelin sensitivity due to its partial dependency on dipolar order, which is particularly prominent in the unique
lipid bilayer structure that makes up myelin. Loss of myelin is inherent to the progression of MS, and many
other neurological disorders. Demonstration of ihMT's sensitivity and specificity to myelin changes in MS
would provide untold benefit not only in detection, but also for monitoring progression and testing
therapies non-invasively. Indeed, preliminary study of ihMT MRI demonstrates a significant correlation with
EDSS, a measure of disability. However MS is a complex disease that not only involves demyelination, but
other processes like inflammation, that may confound state-of-the-art MRI techniques.
We believe quantitative ihMT MRI, which can provide insight into multiple quantitative parameters
associated with the microstructure of the brain and spinal cord, will be able to provide information on
the underlying MS pathology in a non-invasive manner. Confirmation of the information on MS provided by
quantitative ihMT requires comparison with histology, which still represents a gold standard. We aim to provide
such a comparison by application of quantitative ihMT in post-mortem tissues with and without a clinical
diagnosis of MS. This proposed study would serve to determine the quantitative parameters in ihMT that
change in the presence of MS, and histology would confirm how those changes relate to the microstructure of
central nervous system tissue. In order to demonstrate the benefit of quantitative ihMT MRI over other
methods, we also plan to compare quantitative ihMT with other state-of-the-art MRI techniques that have been
applied in prior studies of MS. To allow higher resolution MRI and a more informative comparison with
histology, the bulk of MRI experiments will be conducted on a high field scanner. We will confirm that the
information collected at the higher field strength is applicable at clinical 3T field strength by verifying any
changes in quantitative ihMT parameters are demonstrable at both field strengths.
The information provided by this proposed study on the relationship between quantitative ihMT and
histology would be invaluable to future application of quantitative ihMT MRI for non-invasive
assessment of MS in patients, as well as guiding its use in other neurological disorders.

## Key facts

- **NIH application ID:** 10018119
- **Project number:** 5R21NS114546-02
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Gopal Varma
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $218,750
- **Award type:** 5
- **Project period:** 2019-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018119

## Citation

> US National Institutes of Health, RePORTER application 10018119, Magnetic resonance imaging of human post-mortem tissues with a clinical diagnosis of multiple sclerosis using inhomogeneous magnetization transfer (5R21NS114546-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10018119. Licensed CC0.

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