The corpus callosum (CC) is the most important interhemispheric white matter (WM) structure composed of several anatomically and functionally distinct WM tracts. Resolving these tracts is a challenge since the callosum appears relatively homogenous in conventional structural imaging. Commonly used callosal parcellation methods such as Hofer and Frahm scheme rely on rigid geometric guidelines to separate the substructures that are limited to consider individual variation. Here we present a novel subject-specific and microstructurally-informed method for callosal parcellation based on axonal water fraction (ƒ) known as a diffusion metric reflective of axon caliber and density. We studied 30 healthy subjects from the Human Connectome Project dataset with multi-shell diffusion MRI. The biophysical parameter ƒ was derived from compartment-specific WM modeling. Inflection points were identified where there were concavity changes in ƒ across the CC to delineate callosal subregions. We observed relatively higher ƒ in anterior and posterior areas known to consist of a greater number of small diameter fibers and lower ƒ in posterior body areas of the CC known to consist of a greater number of large diameter fibers. Based on the degree of change in ƒ along the callosum, seven callosal subregions were consistently delineated for each individual. Therefore, this method provides microstructurally informed callosal parcellation in a subject-specific way, allowing for more accurate analysis in the corpus callosum.
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