Quantitative T1 mapping indicates elevated white matter myelin in children with RASopathies.

Background: Evidence suggests pathological roles of myelination in neurodevelopmental disorders, but our understanding is limited. We investigated quantitative T1 mapping (QT1) as a clinically feasible tool for measuring myelination in children with neurodevelopmental disorders of the RAS-MAPK signaling pathway (RASopathies). Methods: We collected QT1, diffusion-weighted, and structural MRI scans from 72 children (49 RASopathies, 23 typical developing (TD)). QT1 measures of myelin content included the macromolecular tissue volume (MTV) in white matter and R1 (1/T1 relaxation) of the cortex. For white matter, we assessed between-groups differences across 39 tracts. For cortical R1, we used principal components analysis to reduce dimensionality and capture myelination patterns across 360 regions. A multivariate ANOVA assessed differences across principal components. Finally, a support vector machine (SVM) identified the most discriminative features between TD and RASopathies. Results: Thirty-four of 39 tracts were higher in MTV in RASopathies relative to TD ( Conclusions: We found widespread elevated myelin in white matter tracts and region-dependent patterns of cortical myelination in children with RASopathies. QT1 enabled us to leverage preclinical models showing oligodendrocyte dysfunction to uncover the myelination pattern