Global and Regional Sex-Related Differences, Asymmetry, and Peak Age of Brain Myelination in Healthy Adults

Background: The fundamental question of normal brain myelination in human is still poorly understood. Methods: Age-dependent global, regional, and interhemispheric sex-related differences in brain myelination of 42 (19 men, 23 women) healthy adults (19-67 years) were explored using the MRI method of fast macromolecular fraction (MPF) mapping. Results: Higher brain myelination in males compared to females was found in global white matter (WM), most WM tracts, juxtacortical WM regions, and putamen. The largest differences between men and women, exceeding 4%, were observed bilaterally in the frontal juxtacortical WM; angular, inferior occipital, and cuneus WM; external capsule; and inferior and superior fronto-orbital fasciculi. The majority of hemispheric differences in MPF were common to men and women. Sex-specific interhemispheric differences were found in juxtacortical WM; men more often had left-sided asymmetry, while women had right-sided asymmetry. Most regions of deep gray matter (GM), juxtacortical WM, and WM tracts (except for projection pathways) showed a later peak age of myelination in women compared to men, with a difference of 3.5 years on average. Body mass index (BMI) was associated with higher MPF and later peak age of myelination independent of age and sex. Conclusions: MPF mapping showed high sensitivity to assess sex-related differences in normal brain myelination, providing the basis for using this method in clinics.