Mapping myelin alterations in Neurofibromatosis Type 1 using Magnetization Transfer and T1W/T2W Ratio Imaging

BackgroundAberrant myelination represents a critical but understudied mechanism in cognitive difficulties associated with neurodevelopmental conditions. Neurofibromatosis 1 (NF1), provides a unique monogenic model to investigate this relationship, as white matter abnormalities are consistently observed, yet their microstructural basis remains uncharacterized. We present the first dual-modality quantitative myelin mapping study in NF1, employing Magnetization Transfer and T1W/T2W ratio imaging to delineate regional myelin alterations. Methods and materialsWe conducted a case-control study of 78 children (58 NF1 and 20 neurotypical controls, ages 11-18 years). Magnetization Transfer Ratio (MTR) and T1-weighted/T2-weighted (T1W/T2W) ratio imaging were used to quantify regional myelin properties. Working memory was assessed using the visuospatial n-back task. ResultsCompared to controls, children with NF1 showed significant myelin reductions in the thalamus, basal ganglia and cerebellum, converging across both imaging modalities. These deficits persisted independent of T2 hyperintensities, indicating a primary myelin pathology. Regional myelin alterations did not correlate with working memory performance. ConclusionThis is the first study to employ two simultaneous methods to characterise myelin differences in NF1. The findings indicate that NF1-related myelin deficits are predominantly confined to the brainstem, cerebellar, and diencephalic structures. These results provide a neurobiological framework for understanding white matter pathology in NF1 and may help guide therapeutic strategies targeting myelination deficits in this disorder.