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

Abstract

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 T2 magnetic resonance imaging combined with multi-T2 fitting, the myelin water fraction (MWF) and geometric-mean of the intra-/extracellular water T2 (geomT2IEW) 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 geomT2IEW 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 geomT2IEW, a significant linear age × 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.

Can MRI measure myelin? Systematic review, qualitative assessment, and meta-analysis of studies validating microstructural imaging with myelin histology

“…This affects the effective transverse relaxation rate (R2*), and can be more directly measured by quantitative susceptibility mapping (QSM). In fact, most MR markers are likely sensitive to multiple biophysical mechanisms and consequently also to various microstructural features of the tissue - for example, relaxation rates may also be influenced by axon diameter and axon packing ( Lynn et al., 2020 ). The biophysical mechanisms underlying myelin-sensitive MR-modalities have been reviewed extensively elsewhere ( Does, 2018 , Edwards, Kirilina, Mohammadi, Weiskopf, 2018 , Möller, Bossoni, Connor, Crichton, Does, Ward, Zecca, Zucca, Ronen, 2019 , Novikov, Fieremans, Jespersen, Kiselev, 2019 ).…”

Role of diffusion kurtosis imaging for detecting brain microstructural changes in complete remission childhood survivors undergoing chemotherapy for acute lymphoblastic leukemia

“…The volume of myelin in the corpus callosum increases sharply in early childhood, reaching 86% of the nal volume at the age of 5 [14,19]. We observed that the patients ≤ 5 years old had signi cantly lower MK and RK after induction, while the patients 5 years old had not undergone similarly signi cant change DKI parameters, in the genu and splenium of CC.…”

Update on myelin imaging in neurological syndromes

“…It has been postulated that posterior brain regions are spared from aging, compared with anterior regions, as occipital lobes showed delayed maturation compared with other lobes, supporting a ‘last-in first-out’ hypothesis of white matter maturation [21]. A study of corpus callosum regions across the lifespan also showed the inverse U-shape, with higher MWF corresponding to regions with greater axon diameter [22]. Another study employed MWI in cognitively unimpaired adults with and without the APOE4 allele.…”