Abstract
Our study investigates the potential of diffusion MRI (dMRI), including diffusion tensor imaging (DTI), fixel-based analysis (FBA) and neurite orientation dispersion and density imaging (NODDI), to detect microstructural tissue abnormalities in rats after mild traumatic brain injury (mTBI). The brains of sham-operated and mTBI rats 35 days after lateral fluid percussion injury were imaged ex vivo in a 11.7-T scanner. Voxel-based analyses of DTI-, fixel- and NODDI-based metrics detected extensive tissue changes in directly affected brain areas close to the primary injury, and more importantly, also in distal areas connected to primary injury and indirectly affected by the secondary injury mechanisms. Histology revealed ongoing axonal abnormalities and inflammation, 35 days after the injury, in the brain areas highlighted in the group analyses. Fractional anisotropy (FA), fiber density (FD) and fiber density and fiber bundle cross-section (FDC) showed similar pattern of significant areas throughout the brain; however, FA showed more significant voxels in gray matter areas, while FD and FDC in white matter areas, and orientation dispersion index (ODI) in areas most damage based on histology. Region-of-interest (ROI)-based analyses on dMRI maps and histology in selected brain regions revealed that the changes in MRI parameters could be attributed to both alterations in myelinated fiber bundles and increased cellularity. This study demonstrates that the combination of dMRI methods can provide a more complete insight into the microstructural alterations in white and gray matter after mTBI, which may aid diagnosis and prognosis following a mild brain injury.
Highlights
Magnetic resonance imaging (MRI) and computed tomography (CT) are routinely used to assess tissue damage in patients after traumatic brain injury (TBI; Duhaime et al, 2010)
The epicenter of the primary lesion in mild TBI (mTBI) animals was at approximately −3.50 mm from bregma, where we found the most extensive significant changes between the groups
These five parameters showed significant decreases (TFCE, p-value < 0.05, family-wise error (FWE)-corrected) in mTBI rats compared to sham-operated ones
Summary
Magnetic resonance imaging (MRI) and computed tomography (CT) are routinely used to assess tissue damage in patients after traumatic brain injury (TBI; Duhaime et al, 2010). Multi-compartment models, such as neurite orientation dispersion and density imaging (NODDI; Zhang et al, 2012), can extract information of volume fractions of isotropic, hindered, and restricted compartments and identify microstructural features associated with pathological process occurring in the brain Both FBA framework and NODDI has been already used to assess tissue alterations after TBI in both animals and humans (Wright et al, 2017; Churchill et al, 2019; Verhelst et al, 2019; Gazdzinski et al, 2020; Palacios et al, 2020; Wallace et al, 2020; McCunn et al, 2021; Muller et al, 2021; Oehr et al, 2021), there are few studies including corroboration of the tissue changes after brain injury with histology
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