Neurite orientation dispersion and density imaging in a rodent model of acute mild traumatic brain injury

Background and Purpose: Identification of changesin brain microstructure following mild traumatic brain injury (mTBI) could be instrumental in understanding the underlying pathophysiology. The purpose of this study was to apply neurite orientation dispersion and density imaging (NODDI) to a rodent model of mTBI to determine whether microstructural changes could be detected immediately following injury. Methods: Fifteen adult male Wistar rats were scanned on a Bruker 9.4 Tesla small animal MRI using a multi-shell acquisition (30 b = 1000 s/mm2 and 60 b = 2000 s/mm2). Nine animals experienced a single closed head controlled cortical impact followed by NODDI from 1 to 4 h post injury. Region of interest analysis focused on the corpus callosum and hippocampus. A mixed analysis of variance (ANOVA) was used to determine statistically significant interactions in neurite density index (NDI), orientation dispersion index (ODI), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity. Follow up repeated-measures ANOVAs were used to determine individual changes over time. Results: NDI showed a significant increase in the hippocampus and corpus callosum following injury, while ODI showed increases in the corpus callosum. No significant changes were observed in the sham control animals. No changes were found in FA, MD, AD, or RD. Histological analysis revealed increased glial fibrillary acidic protein staining relative to controls in both the hippocampus and corpus callosum, with evidence of activated astrocytes in these regions. Conclusions: Changes in NODDI metrics were detected as early as 1 h following mTBI. No changes were detected with conventional diffusion tensor imaging (DTI) metrics, suggesting that NODDI provides greater sensitivity to microstructural changes than conventional DTI.