High-resolution imaging of distinct human corpus callosum microstructure and topography of structural connectivity to cortices at high field

Characterization of the microstructural properties and topography of the human corpus callosum (CC) is key to understanding interhemispheric neural communication and brain function. In this work, we tested the hypothesis that high-resolution T ₁ relaxometry at high field has adequate sensitivity and specificity for characterizing microstructural properties of the human CC, and elucidating the structural connectivity of the callosal fibers to the cortices of origin. The high-resolution parametric T ₁ images acquired from healthy subjects (N = 16) at 7 T clearly showed a consistent T ₁ distribution among individuals with substantial variation along the human CC axis, which is highly similar to the spatial patterns of myelin density and myelinated axon size based on the histology study. Compared to the anterior part of the CC, the posterior midbody and splenium had significantly higher T ₁ values. In conjunction with T ₁ -based classification method, the splenial T ₁ values were decoded more reliably compared to a conventional partitioning method, showing a much higher T ₁ value in the inferior splenium than in the middle/superior splenium. Moreover, the T ₁ profile of the callosal subdivision represented the topology of the fiber connectivity to the projected cortical regions: the fibers in the posterior midbody and inferior splenium with a higher T ₁ (inferring a larger axon size) were mainly connected to motor–sensory and visual cortical areas, respectively; in contrast, the fibers in the anterior/posterior CC with a lower T ₁ (inferring a smaller axon size) were primarily connected to the frontal/parietal–temporal areas. These findings indicate that high-resolution T ₁ relaxometry imaging could provide a complementary and robust neuroimaging tool, useful for exploring the complex tissue properties and topographic organization of the human corpus callosum.