Exploring IVIM-DKI and DKI for Assessing Microvascular and Microstructural Changes After Traumatic Brain Injury

Traumatic brain injury (TBI) is a major public health concern, but no reliable markers of injury are available. Axonal and microvascular changes are common after TBI, and diffusion MRI offers sensitivity to both. Diffusion kurtosis imaging (DKI) probes tissue microstructure, while intravoxel incoherent motion (IVIM) reflects microvascular flows. This study evaluated whether DKI or combined IVIM-DKI analysis could detect microstructural and microvascular alterations after TBI and compared the sensitivity of these methods to the standard diffusion tensor imaging (DTI) and IVIM models. Longitudinal DKI and IVIM-DKI changes were investigated following controlled cortical impact (CCI) in mice at 3, 10, and 22 days post-injury. For this, parametric maps were obtained which for DKI included fractional anisotropy (FA), axial, radial, and mean diffusivity (AD, RD, and MD), axial, radial, and mean kurtosis (AK, RK, and MK). For IVIM-DKI, we obtain perfusion fraction (f), pseudo-diffusion coefficient (D^*), diffusivity (D), and powder kurtosis ( $\dot{K}$ ). Additionally, results for the non-kurtosis metrics were compared to results for the corresponding metrics as estimated by the standard DTI and IVIM models. Widespread increases in MD, AD, and RD were present in white and gray matter on Day 3 post-injury. On Day 10, these increases were replaced by focally decreased FA and AD in white matter, and increased f in the ipsilateral cortex. On Day 22, decreases in FA and AD were progressively widespread in white matter and accompanied by decreased MD, MK, AK, and RK. Standard DTI revealed less widespread differences at all time points, and standard IVIM detected no significant differences in f. These results show DKI and IVIM-DKI as promising tools for assessing microstructural and microvascular alterations after TBI. DKI captured widespread white matter changes and early gray matter alterations, while IVIM-DKI detected intermediate changes in f in gray matter. Both methods captured additional injury-related differences compared to standard DTI and IVIM.