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Updated: Aug 27, 2025
Magnetic Resonance Imaging of Multiple Sclerosis at 7.0 Tesla
Published on: February 19, 2021
Evaluating brain damage in multiple sclerosis with simultaneous multi-angular-relaxometry of tissue
Biao Xiang1, Jie Wen1, Robert E Schmidt2
1Department of Radiology, Washington University, St. Louis, Missouri, 63110, USA.
Objective:
Multiple sclerosis (MS) is a common demyelinating central nervous system disease. MRI methods that can quantify myelin loss are needed for trials of putative remyelinating agents. Quantitative magnetization transfer MRI introduced the macromolecule proton fraction (MPF), which correlates with myelin concentration. We developed an alternative approach, Simultaneous-Multi-Angular-Relaxometry-of-Tissue (SMART) MRI, to generate MPF. Our objective was to test SMART-derived MPF metric as a potential imaging biomarker of demyelination.
Methods:
Twenty healthy control (HC), 11 relapsing-remitting MS (RRMS), 22 progressive MS (PMS), and one subject with a biopsied tumefactive demyelinating lesion were scanned at 3T using SMART MRI. SMART-derived MPF metric was determined in normal-appearing cortical gray matter (NAGM), normal-appearing subcortical white matter (NAWM), and demyelinating lesions. MPF metric was evaluated for correlations with physical and cognitive test scores. Comparisons were made between HC and MS and between MS subtypes. Furthermore, correlations were determined between MPF and neuropathology in the biopsied person.
Results:
SMART-derived MPF in NAGM and NAWM were lower in MS than HC (p < 0.001). MPF in NAGM, NAWM and lesions differentiated RRMS from PMS (p < 0.01, p < 0.001, p < 0.001, respectively), whereas lesion volumes did not. MPF in NAGM, NAWM and lesions correlated with the Expanded Disability Status Scale (p < 0.01, p < 0.001, p < 0.001, respectively) and nine-hole peg test (p < 0.001, p < 0.001, p < 0.01, respectively). MPF was lower in the histopathologically confirmed inflammatory demyelinating lesion than the contralateral NAWM and increased in the biopsied lesion over time, mirroring improved clinical performance.
Interpretation:
SMART-derived MPF metric holds potential as a quantitative imaging biomarker of demyelination and remyelination.
Insights
New Simultaneous-Multi-Angular-Relaxometry-of-Tissue (SMART) MRI can measure macromolecule proton fraction (MPF) to detect demyelination in multiple sclerosis (MS). This quantitative imaging biomarker shows potential for tracking disease progression and treatment response.
Area of Science:
- Neuroimaging
- Biomarker Discovery
- Demyelinating Diseases
Background:
- Multiple sclerosis (MS) is a central nervous system disease characterized by myelin loss.
- Accurate quantification of myelin is crucial for evaluating new remyelinating therapies.
- Quantitative magnetization transfer MRI provides macromolecule proton fraction (MPF) as a myelin correlate.
Purpose of the Study:
- To introduce Simultaneous-Multi-Angular-Relaxometry-of-Tissue (SMART) MRI as an alternative method for generating MPF.
- To assess the utility of SMART-derived MPF as an imaging biomarker for demyelination in MS.
Main Methods:
- SMART MRI was performed at 3T on healthy controls (HC) and MS patients (RRMS and PMS).
- SMART-derived MPF was measured in normal-appearing gray matter (NAGM), white matter (NAWM), and demyelinating lesions.
- MPF was correlated with clinical scores and neuropathology in a biopsied lesion.
Main Results:
- SMART-derived MPF was lower in MS patients compared to HC in both NAGM and NAWM.
- MPF metrics differentiated between relapsing-remitting MS (RRMS) and progressive MS (PMS) subtypes.
- MPF correlated significantly with physical and cognitive disability scores and neuropathological findings.
Conclusions:
- SMART-derived MPF is a sensitive imaging biomarker for demyelination in MS.
- This metric has the potential to monitor disease progression and therapeutic effects in MS clinical trials.
