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Although rodent models are a predominant study model in neuroscienceresearch, research investigating healthy rodent brain maturation remainslimited. This motivates further study of normal brain maturation in rodents toexclude confounds of developmental changes from interpretations of diseasemechanisms. 11 C57Bl/6 mice (6 males) were scanned longitudinally at 3, 4, 5,and 8 months of age using frequency-dependent and tensor-valued diffusion MRI(dMRI), and Magnetization Transfer saturation (MTsat) MRI. Total kurtosisshowed significant increases over time in all regions, which was driven byincreases in isotropic kurtosis while anisotropic kurtosis remained stable.Increases in total and isotropic kurtosis with age were matched with increasesin MTsat. Quadratic fits revealed that most metrics show a maximum/minimumaround 5-6 months of age. Most dMRI metrics revealed significantly differenttrajectories between males and females, while the MT metrics did not. Linearfits between kurtosis and MT metrics highlighted that changes in total kurtosisfound throughout normal brain development are driven by isotropic kurtosis,while differences in total kurtosis between brain regions are driven byanisotropic kurtosis. Overall, the trends observed in conventional dMRI and MTmetrics are comparable to previous studies on normal brain development, whilethe trajectories of our more advanced dMRI metrics provide novel insight. Basedon the developmental trajectories of tensor-valued dMRI and MT metrics, ourresults suggest myelination during brain maturation is not a main contributorto microscopic diffusion anisotropy and anisotropic kurtosis in axons. Forstudies that only calculate total kurtosis, we suggest caution in attributingneurobiological changes to changes in total kurtosis as we show here constantanisotropic kurtosis in the presence of increasing myelin content.

Tensor-valued and frequency-dependent diffusion MRI and magnetization transfer saturation MRI evolution during adult mouse brain maturation