# Multimodal, quantitative MRI in the lumbosacral spinal cord in progressive multiple sclerosis

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $478,273

## Abstract

PROJECT SUMMARY
Clinical disability in multiple sclerosis (MS) is largely determined by the accumulation of demyelinating lesions
in the spinal cord (SC), but conventional magnetic resonance imaging (MRI) methods lack the sensitivity to
assess the full extent of SC pathology including sub-radiological tissue damage that occurs beyond MRI-visible
lesions. Recent studies have revealed that cervical SC pathology correlates with disability in MS and is
independent from MRI measures of disease in the brain. However, a lack of evidence on disease in the
lumbosacral spinal cord (LSC) has limited our ability to fully understand primary progressive MS (PPMS)
pathology and how LSC lesions and diffuse damage impact clinical disability and autonomic function, which
hinders the selection and evaluation of therapies for patients. Advancing multimodal MRI and developing
imaging biomarkers of PPMS targeting the LSC will deliver more accurate assessments of disease
progression, enabling and informing decisions regarding treatment with disease-modifying therapies or
symptom management strategies. Our long-term goal is to develop MRI biomarkers of MS pathology for the
complete SC. We predict that MRI measures of the entire spinal axis will better inform clinicians on the extent
of disease, which will likely dictate therapy. Our project objective is to identify and validate quantitative MRI
biomarkers in the lower SC that are associated with clinical disability in PPMS. Our previous work
demonstrated that advanced MRI methods (diffusion tensor imaging, quantitative magnetization transfer MRI,
and resting-state functional MRI) provide measures related to pathology in the cervical and lumbar SC in
relapsing-remitting MS, and we will now study the extent of imaging abnormalities in the LSC by applying these
advanced MRI methods in PPMS. We also extend advanced MRI to the conus and cauda equina to explore
associations between imaging indices and autonomic dysfunction seen in PPMS patients. Our specific aims
are: (1) Establish reproducibility and validate quantitative MRI indices in the LSC, (2) Characterize quantitative
MRI biomarkers of disease pathology in the LSC for PPMS in relation to clinical disability, and (3) Optimize the
resolution of quantitative MRI methods to extend their application to the conus medullaris and cauda equina.
This research is technically innovative because it refines advanced MRI methods for application in the LSC; to
our knowledge, this will be the first application of these methods to the conus and cauda equina. The resulting
novel, quantitative MRI biomarkers of PPMS pathology in these structures will complement existing brain and
cervical SC MRI in monitoring disease progression and treatment response. The results will improve our
understanding of the pathological substrates of disability in PPMS, which is expected to have a significant
impact on future studies of potential therapies. The MRI methods will also benefit studies of other ne...

## Key facts

- **NIH application ID:** 10856232
- **Project number:** 1R01NS136316-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Kristin Poole O'Grady
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $478,273
- **Award type:** 1
- **Project period:** 2024-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10856232

## Citation

> US National Institutes of Health, RePORTER application 10856232, Multimodal, quantitative MRI in the lumbosacral spinal cord in progressive multiple sclerosis (1R01NS136316-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10856232. Licensed CC0.

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