Comparison of Pediatric Demyelinating Diseases using Axonal and Myelin-Sensitive MRI

Demyelinating diseases constitute the most frequent cause of non-traumatic neurological disability in the pediatric population. Conventional MRI, while sensitive to focal white matter injury, lacks specificity to discern between edema, demyelination and axonal loss. This study aimed to employ advanced MRI biomarkers-specifically macromolecular tissue volume (MTV) and neurite orientation dispersion and density imaging (NODDI)-derived metrics-to assess myelin integrity (myelin volume fraction, MVF), axonal density (neurite density index, NDI), and the g-ratio in pediatric patients with multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).

Thirty-nine pediatric patients (MS, n = 15; NMOSD, n = 6; MOGAD, n = 11), including 7 age-matched heathy controls, underwent 3 Tesla MRI as part of a cross-sectional study. Multi-echo gradient echo and multi-shell diffusion sequences were acquired to compute MTV and NODDI metrics. Lesional and normal-appearing white matter (NAWM) were segmented, and imaging metrics (MVF, NDI, and g-ratio) were compared across groups. Correlations between imaging biomarkers and clinical measures were also examined.

MS demonstrated significantly higher lesional g-ratio than MOGAD (p = 0.02) and NMOSD (p = 0.02) and lower MVF than NMOSD (p = 0.006), indicating greater relative myelin loss. NAWM partitioning identified higher deep-NAWM ODI in MS patients than controls (p = 0.04). Within the MS cohort, 25ftW was associated with g-ratio, MVF, and NDI measures for both whole-brain and deep NAWM.

Advanced MRI biomarkers provide a more nuanced characterization of microstructural alterations in pediatric demyelinating diseases. The distinct imaging profiles-highlighting greater demyelination in MS versus MOGAD and NMOSD-support the utility of these metrics for targeted clinical management and therapeutic stratification. Future longitudinal studies are warranted to further validate their role in monitoring disease progression and treatment response.