Related Experiment Video
Updated: Aug 5, 2026
Magnetic Resonance Imaging of Multiple Sclerosis at 7.0 Tesla
Published on: February 19, 2021
MRI Markers of EDSS ≥ 3 in Relapsing-Remitting Multiple Sclerosis: An Assessment of Lesion Burden, Brain Volumetry,
Sami A Alghamdi1, Othman I Alomair1, Manal H Alosaimi1
1Radiological Sciences Department, College of Applied Medical Sciences, King Saud University, P.O. Box 145111, Riyadh 4545, Saudi Arabia.
Abstract:
Background/Objectives: Disability in relapsing-remitting multiple sclerosis (RRMS) reflects multiple pathological processes that may not be fully captured by individual MRI markers. Because an EDSS score ≥ 3 represents a clinically meaningful threshold of moderate-to-higher disability, this study evaluated the cross-sectional ability of brain volumetric measures and IVIM-DWI parameters to identify patients with RRMS who had EDSS ≥ 3. Methods: This retrospective cross-sectional study included 189 patients with RRMS who had complete EDSS, lesion count, IVIM-DWI, and brain volumetric MRI data. Patients were stratified into EDSS < 3 and EDSS ≥ 3 groups. Single-marker ROC analyses were performed for lesion count, IVIM-DWI parameters, absolute volumetric measures, and fractional volumetric measures. Combined ROC models were constructed to assess the discriminatory performance of integrating lesion burden, volumetric MRI, and IVIM-DWI metrics. Internal model stability was evaluated using 5-fold cross-validation. Results: Patients with EDSS ≥ 3 had higher lesion count, higher ADC and D values, lower gray matter, white matter, and brain parenchymal volumes, higher CSF volume, higher CSF fraction, and lower brain parenchymal fraction (BPF). In single-marker ROC analysis, BPF and CSF fraction showed the strongest discriminatory performance (AUC = 0.705), followed by lesion count (AUC = 0.696), whereas absolute BV showed minimal discriminatory value (AUC = 0.503). The core lesion count + BPF model achieved an AUC of 0.757 and a cross-validated AUC of 0.737. Adding perfusion fraction (f) produced the numerically highest cross-validated performance, with an AUC of 0.769 and a cross-validated AUC of 0.746, although the incremental improvement over lesion count + BPF was modest and not statistically significant. Conclusions: Fractional volumetric measures showed stronger discriminatory performance than absolute BV for EDSS ≥ 3 stratification in RRMS. The lesion count + BPF + f model achieved the highest cross-validated performance among the evaluated MRI models; however, overall discrimination was moderate, and the incremental improvement associated with f was not statistically significant. These exploratory findings require evaluation in larger longitudinal cohorts with external validation.
Insights
Fractional brain volumes and lesion counts better identify moderate-to-severe disability in relapsing-remitting multiple sclerosis (RRMS) than absolute volumes. Combining these MRI markers showed moderate diagnostic performance.
Area of Science:
- Neurology
- Radiology
- Medical Imaging
Background:
- Disability in relapsing-remitting multiple sclerosis (RRMS) arises from complex pathologies potentially missed by single MRI markers.
- A score of 3 or higher on the Expanded Disability Status Scale (EDSS) signifies clinically meaningful moderate-to-severe disability.
Purpose of the Study:
- To assess the cross-sectional ability of brain volumetric measures and IVIM-DWI parameters to identify RRMS patients with EDSS ≥ 3.
- To compare the discriminatory performance of absolute versus fractional volumetric measures.
Main Methods:
- Retrospective analysis of 189 RRMS patients with complete MRI (volumetric, IVIM-DWI) and EDSS data.
- Stratification into EDSS < 3 and EDSS ≥ 3 groups.
- Receiver Operating Characteristic (ROC) analyses of individual and combined MRI markers, including lesion count, IVIM-DWI parameters, and volumetric measures (absolute and fractional).
Main Results:
- Patients with EDSS ≥ 3 exhibited higher lesion counts, higher ADC and D values, lower gray matter, white matter, and brain parenchymal volumes, and higher CSF volume and fraction, alongside lower brain parenchymal fraction (BPF).
- BPF and CSF fraction demonstrated the strongest single-marker discrimination (AUC=0.705), outperforming lesion count (AUC=0.696) and absolute brain volume (AUC=0.503).
- A combined model of lesion count + BPF achieved an AUC of 0.757, with the addition of perfusion fraction (f) yielding the highest cross-validated AUC of 0.746, though with modest, non-significant improvement.
Conclusions:
- Fractional volumetric measures, particularly BPF, are more effective than absolute brain volumes for stratifying RRMS disability (EDSS ≥ 3).
- The combination of lesion count, BPF, and perfusion fraction (f) showed the highest performance among evaluated MRI models, though overall discrimination was moderate.
- Further validation in larger, longitudinal cohorts is warranted to confirm these exploratory findings and the incremental value of IVIM-DWI parameters.
