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Updated: Feb 28, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Distinct microstructural white matter alterations in demyelinating diseases: Insights from myelin- and axon-sensitive
Yasunobu Hoshino1, Akifumi Hagiwara2, Yuji Tomizawa1
1Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Objectives:
We aimed to compare microstructural white matter alterations in multiple sclerosis (MS), anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders (AQP4-NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) using advanced quantitative MRI.
Methods:
This retrospective study included 84 participants (24 MS, 18 AQP4-NMOSD, 20 MOGAD, and 22 healthy controls). Quantitative MR relaxometry and multi-shell diffusion-weighted imaging were acquired at 3 T to derive myelin volume fraction (MVF), axonal volume fraction, g-ratio, and diffusion tensor metrics. Normal-appearing white matter (NAWM) was analyzed in all patients, and plaque-based analyses were performed in patients with focal white matter lesions (20 MS, 8 AQP4-NMOSD, 8 MOGAD). Diagnostic performance was assessed using receiver operating characteristic (ROC) analyses.
Results:
In NAWM, MS showed significantly lower fractional anisotropy than MOGAD or controls (P < 0.05), and AQP4-NMOSD exhibited lower MVF than MOGAD (P < 0.05). Among patients with lesions, plaques in MS had significantly lower MVF and higher g-ratio than those in AQP4-NMOSD (P < 0.0001) and MOGAD (P < 0.05). Plaques in AQP4-NMOSD showed a lower g-ratio than MOGAD (P < 0.01). Univariate ROC analyses revealed that plaque g-ratio distinguished AQP4-NMOSD from MS (AUC 0.92 [95%CI, 0.82-1.00], sensitivity 100.0%, specificity 75.0%) and from MS + MOGAD (AUC 0.88 [0.77-0.99], sensitivity 100.0%, specificity 75.0%). A multivariate model combining NAWM and plaque metrics further improved discrimination (AUC 0.95 [0.88-1.00], sensitivity 75.0%, specificity 95.0%, and AUC 0.91 [0.81-1.00], sensitivity 50.0%, specificity 92.9%).
Conclusion:
Quantitative MRI metrics-especially MVF and g-ratio-demonstrate distinct microstructural profiles among MS, AQP4-NMOSD, and MOGAD, enabling improved disease differentiation.
Insights
Quantitative MRI reveals distinct white matter changes in multiple sclerosis (MS), anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders (AQP4-NMOSD), and MOGAD. These advanced imaging metrics aid in differentiating these neurological conditions.
Area of Science:
- Neuroimaging
- Neurology
- Biomedical Engineering
Background:
- Multiple Sclerosis (MS), AQP4-NMOSD, and MOGAD are distinct inflammatory demyelinating diseases of the central nervous system.
- Distinguishing between these conditions is crucial for appropriate treatment and management.
- Microstructural white matter alterations are key pathological features in these diseases.
Purpose of the Study:
- To compare white matter microstructural alterations across MS, AQP4-NMOSD, and MOGAD using advanced quantitative MRI techniques.
- To identify MRI metrics that can effectively differentiate between these three neurological disorders.
Main Methods:
- Retrospective analysis of 84 participants (24 MS, 18 AQP4-NMOSD, 20 MOGAD, 22 controls).
- Acquisition of quantitative MR relaxometry and multi-shell diffusion-weighted imaging at 3T.
- Derivation of myelin volume fraction (MVF), axonal volume fraction, g-ratio, and diffusion tensor metrics in normal-appearing white matter (NAWM) and focal lesions.
Main Results:
- MS showed lower fractional anisotropy in NAWM compared to MOGAD and controls.
- AQP4-NMOSD exhibited lower MVF in NAWM than MOGAD.
- Plaques in MS had significantly lower MVF and higher g-ratio than in AQP4-NMOSD and MOGAD.
- Plaque g-ratio effectively distinguished AQP4-NMOSD from MS and combined MS+MOGAD (AUC up to 0.92).
- A multivariate model combining NAWM and plaque metrics achieved high diagnostic performance (AUC up to 0.95).
Conclusions:
- Quantitative MRI metrics, particularly MVF and g-ratio, reveal unique microstructural profiles for MS, AQP4-NMOSD, and MOGAD.
- These advanced MRI metrics significantly enhance the ability to differentiate between these distinct neurological diseases.
