Quantitative T1 Mapping Indicates Elevated White Matter Myelin in Children With RASopathies

Area of Science:

• Neuroimaging
• Developmental Neuroscience
• Biomedical Engineering

Background:

• Myelination plays a pathological role in neurodevelopmental disorders, often linked to cognitive deficits.
• In vivo assessment of myelination in these disorders is challenging.
• Quantitative T1 mapping (QT1) shows promise for reliable myelin measurement.

Purpose of the Study:

• To investigate QT1 for measuring myelination in children with RASopathies.
• To assess differences in white matter and cortical myelination between children with RASopathies and typically developing children.
• To explore the potential of QT1 as a tool for identifying and monitoring myelin alterations in neurodevelopmental disorders.

Main Methods:

• Collected QT1, diffusion-weighted, and structural MRI scans from 72 children (49 RASopathies, 23 TD).
• Measured white matter myelination using macromolecular tissue volume (MTV) and cortical myelination using R1.
• Utilized principal components analysis, MANOVA, and support vector machine (SVM) for group comparisons and feature identification.

Main Results:

• Widespread elevated white matter tract MTV in RASopathies compared to TD (34/39 tracts, pFDR<.05).
• Significant group effect on cortical R1 (p=.002), indicating differences in cortical myelination.
• SVM achieved 87% accuracy, identifying cognitive and cortical R1 features as most discriminative.

Conclusions:

• Children with RASopathies exhibit widespread elevated white matter myelin and region-dependent cortical myelination patterns.
• QT1 revealed precocious myelination, potentially linked to oligodendrocyte dysfunction.
• QT1 is a promising tool for myelin assessment and therapeutic target identification in neurodevelopmental disorders.