Isotropic diffusional kurtosis as a marker of glial cell content and diversification during brain maturation

Motivation: Healthy rodent brain maturation research remains limited, although rodents are a predominant study model, which motivates further study to exclude confounds of developmental changes from pathophysiological interpretations. Goal(s): Our goals were to investigate how microstructural MRI metrics change over the course of brain maturation and disentangle what changes in these metrics may indicate on a neurobiological level. Approach: 11 mice were scanned at 9.4T between 3-8 months of age, with histology (n=4) performed at 3 and 8 months. Results: Total diffusional kurtosis and myelin-specific metrics showed significant increases over time, paired with increased isotropic kurtosis and increased histological oligodendrocyte and astrocyte content. Impact: This work shows that there are ongoing microstructural changes even after mice are considered “adults”, detectable by isotropic kurtosis. We provide new interpretations of diffusion MRI changes during brain maturation, with evidence of the underlying mechanisms impacting isotropic kurtosis.