Microstructure of Human Corpus Callosum across the Lifespan: Regional Variations in Axon Caliber, Density, and Myelin Content

The myeloarchitecture of the corpus callosum (CC) is characterized as a mosaic of distinct differences in fiber density of small-and large-diameter axons along the anterior-posterior axis; however, regional and age differences across the lifespan are not fully understood. Using multiecho T-2 magnetic resonance imaging combined with multi-T-2 fitting, the myelin water fraction (MWF) and geometric-mean of the intra-/extracellular water T-2 (geomT(2IEW)) in 395 individuals (7-85 years; 41% males) were examined. The approach was validated where regional patterns along the CC closely resembled the histology; MWF matched mean axon diameter and geomT(2IEW) mirrored the density of large-caliber axons. Across the lifespan, MWF exhibited a quadratic association with age in all 10 CC regions with evidence of a positive linear MWF-age relationship among younger participants and minimal age differences in the remainder of the lifespan. Regarding geomT(2IEW), a significant linear age x region interaction reflected positive linear age dependence mostly prominent in the regions with the highest density of small-caliber fibers-genu and splenium. In all, these two indicators characterize distinct attributes that are consistent with histology, which is a first. In addition, these results conform to rapid developmental progression of CC myelination leveling in middle age as well as age-related degradation of axon sheaths in older adults.

Automated summary

The myeloarchitecture of the corpus callosum was studied using magnetic resonance imaging, revealing age and region-related patterns in myelin water fraction and intra-/extracellular water T-2, which were consistent with histology. These two indicators were associated with axon diameter and density, showing different patterns across age groups.