Early Microstructural and Metabolic Changes following Controlled Cortical Impact Injury in Rat: A Magnetic Resonance Imaging and Spectroscopy Study

Understanding tissue alterations at an early stage following traumatic brain injury (TBI) is critical for injury management and limiting severe consequences from secondary injury. We investigated the early microstructural and metabolic profiles using in vivo diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy (H-1 MRS) at 2 and 4 h following a controlled cortical impact injury in the rat brain using a 7.0 Tesla animal MRI system and compared profiles to baseline. Significant decrease in mean diffusivity (MD) and increased fractional anisotropy (FA) was found near the impact site (hippocampus and bilateral thalamus; p < 0.05) immediately following TBI, suggesting cytotoxic edema. Although the DTI parameters largely normalized on the contralateral side by 4 h, a large inter-individual variation was observed with a trend towards recovery of MD and FA in the ipsilateral hippocampus and a sustained elevation of FA in the ipsilateral thalamus (p < 0.05). Significant reduction in metabolite to total creatine ratios of N-acetylaspartate (NAA, p = 0.0002), glutamate (p = 0.0006), myoinositol (Ins, p = 0.04), phosphocholine and glycerophosphocholine (PCh + GPC, p = 0.03), and taurine (Tau, p = 0.009) were observed ipsilateral to the injury as early as 2 h, while glutamine concentration increased marginally (p = 0.07). These metabolic alterations remained sustained over 4 h after TBI. Significant reductions of Ins (p = 0.024) and Tau (p = 0.013) and marginal reduction of NAA (p = 0.06) were also observed on the contralateral side at 4 h after TBI. Overall our findings suggest significant microstructural and metabolic alterations as early as 2 h following injury. The tendency towards normalization at 4 h from the DTI data and no further metabolic changes at 4 h from MRS suggest an optimal temporal window of about 3 h for interventions that might limit secondary damage to the brain. Results indicate that early assessment of TBI patients using DTI and MRS may provide valuable information on the available treatment window to limit secondary brain damage.