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, but its precise involvement remains unclear.
• RASopathies, disorders of the RAS-MAPK signaling pathway, are associated with neurodevelopmental challenges.
• Quantitative T1 mapping (QT1) is a promising MRI technique for assessing myelination in vivo.

Purpose of the Study:

• To investigate quantitative T1 mapping (QT1) as a method for measuring myelination in children with RASopathies.
• To characterize white matter and cortical myelination patterns in children with RASopathies compared to typical developing children.
• To identify potential imaging biomarkers for neurodevelopmental disorders.

Main Methods:

• Acquired QT1, diffusion-weighted, and structural MRI scans from 72 children (49 RASopathies, 23 typical developing).
• Assessed white matter myelination using macromolecular tissue volume (MTV) in 39 tracts.
• Analyzed cortical myelination using R1 relaxation rates across 360 regions and employed principal components analysis and support vector machine (SVM).

Main Results:

• Children with RASopathies exhibited significantly higher MTV in 34 of 39 white matter tracts compared to controls.
• A significant group effect on cortical R1 (myelination) was observed, indicating differences between RASopathies and typical developing children.
• SVM analysis achieved 87% accuracy in discriminating between groups, identifying cognitive and cortical R1 features as key discriminators.

Conclusions:

• QT1 revealed widespread white matter hypermyelination and region-dependent cortical myelination patterns in children with RASopathies.
• These findings highlight myelin as a potential therapeutic target in neurodevelopmental disorders.
• QT1 is a valuable tool for identifying and monitoring myelination abnormalities in vivo, advancing therapeutic strategies.