Diffusion kurtosis as an in vivo imaging marker for reactive astrogliosis in traumatic brain injury

Diffusion Kurtosis Imaging (DKI) provides quantifiable information on the non-Gaussian behavior of water diffusion in biological tissue. Changes in water diffusion tensor imaging (DTI) parameters and DKI parameters in several white and gray matter regions were investigated in a mild controlled cortical impact (CCI) injury rat model at both the acute (2 h) and the sub-acute (7 days) stages following injury. Mixed model ANOVA analysis revealed significant changes in temporal patterns of both DTI and DKI parameters in the cortex, hippocampus, external capsule and corpus callosum. Post-hoc tests indicated acute changes in mean diffusivity (MD) in the bilateral cortex and hippocampus (p<0.0005) and fractional anisotropy (FA) in ipsilateral cortex (p<0.0005), hippocampus (p=0.014), corpus callosum (p=0.031) and contralateral external capsule (p=0.011). These changes returned to baseline by the sub-acute stage. However, mean kurtosis (MK) was significantly elevated at the sub-acute stages in all ipsilateral regions and scaled inversely with the distance from the impacted site (cortex and corpus callosum: p<0.0005; external capsule: p=0.003; hippocampus: p=0.011). Further, at the sub-acute stage increased MK was also observed in the contralateral regions compared to baseline (cortex: p=0.032; hippocampus: p=0.039) while no change was observed with MD and FA. An increase in mean kurtosis was associated with increased reactive astrogliosis from immunohistochemistry analysis. Our results suggest that DKI is sensitive to microstructural changes associated with reactive astrogliosis which may be missed by standard DTI parameters alone. Monitoring changes in MK allows the investigation of molecular and morphological changes in vivo due to reactive astrogliosis and may complement information available from standard DTI parameters. To date the use of diffusion tensor imaging has been limited to study changes in white matter integrity following traumatic insults. Given the sensitivity of DKI to detect microstructural changes even in the gray matter in vivo, allows the extension of the technique to understand patho-morphological changes in the whole brain following a traumatic insult.