# Investigation of discrete neurodegenerative changes of the in vivo multiple sclerosis spinal cord using 7T MRI

> **NIH NIH R21** · CLEVELAND CLINIC LERNER COM-CWRU · 2024 · $241,500

## Abstract

Project Summary
People with multiple sclerosis (PwMS) with an insidious clinical decline independent of
inflammatory disease activity (progression) often have a greater extent of spinal cord (SC)
involvement. There is a critical need to understand how injury of clinically eloquent SC motor
and sensory tracts can lead to variable functional impairment ranging from being asymptomatic
to a bedridden state. Strong correlations between disability worsening and a progressive
disease course have been observed with 1) focal atrophy with some lateral SC lesions and 2)
upper cervical SC atrophy reflecting global SC lesion burden. These findings suggest that
axonal loss is a key driver of disability and is variably lost as a consequence of lesions. In
postmortem tissue, we determined that T2*-weighted intensity can be used to discriminate
demyelinated hyperintense lesions from myelinated lesions (intermediate hyperintensity).
Approximately a third of T2* lesions were intermediate intensity characterized by swollen
dystrophic axons with thinner myelin and activated/phagocytic microglia/macrophages. This led
to our hypothesis that intermediate lesions represent secondary neurodegenerative changes
(Wallerian degeneration) distal to a demyelinated lesion. Our aims determine whether 1)
intermediate lesions can be detected distinctly from hyperintense lesions in vivo and whether
they are distal to hyperintense lesions using 7T MRI; and 2) differences in detection of
intermediate lesions between 7T and 3T. We are particularly well positioned to perform this work
as we have demonstrated T2* can be thresholded to discriminate between lesion subtypes by
MRI-pathology and have similar sequences already available in a pre-existing 3T MRI dataset
and prospectively on 7T. The 52% improved detection of 7T lesions compared to 3T and our
ability to pre-screen PwMS with known focal cervical SC lesions at our Center, will optimize the
potential for successful execution of our aims. Ultimately, the data generated from this proposal
will identify the ability of 7T and 3T to detect potential neurodegenerative changes distal to
demyelination to ask what patient characteristics lead to a greater likelihood of Wallerian
degeneration (intermediate lesions) or axonal loss (atrophy) and whether therapeutic
interventions can prevent these processes.

## Key facts

- **NIH application ID:** 10868830
- **Project number:** 1R21NS136961-01
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Kedar Mahajan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $241,500
- **Award type:** 1
- **Project period:** 2024-07-18 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10868830

## Citation

> US National Institutes of Health, RePORTER application 10868830, Investigation of discrete neurodegenerative changes of the in vivo multiple sclerosis spinal cord using 7T MRI (1R21NS136961-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10868830. Licensed CC0.

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