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

Abstract

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 ((1)H 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), myo-inositol (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.

Ex Vivo Diffusion Tensor Imaging of Spinal Cord Injury in Rats of Varying Degrees of Severity

“…Following cortical impact and the resulting axonal damage, there is a decrease in MD and an increase in FA suggestive of cytotoxic edema. 30 Changes in tissue structure in regions outside the lesion site attributed to cytotoxic inflammatory products were implicated in this brain study. 30 In general, there is strong evidence of changes in the number of inflammatory cells at locations away from the injury site and even outside of the spinal cord.…”

“…30 Changes in tissue structure in regions outside the lesion site attributed to cytotoxic inflammatory products were implicated in this brain study. 30 In general, there is strong evidence of changes in the number of inflammatory cells at locations away from the injury site and even outside of the spinal cord. [31][32][33][34][35] The activation of the inflammatory processes helps to explain the FIG.…”

The Effects of Perturbed Cerebral Blood Flow and Cerebrovascular Reactivity on Structural MRI and Behavioral Readouts in Mild Traumatic Brain Injury

“…The patterns of T 2 , ADC, and FA changes after TBI are in general agreement with those reported from our previous studies 8,36 and other studies. [37][38][39] In the impacted region (R0I-1), average CBF reached ischemic levels (⩽20% of normal) at 1 and 3 hours, which is expected to cause ischemia and to manifest in detectable T 2 and ADC changes as observed. Interestingly, at 14 days there were no apparent large infarcts detected based on MRI and behavioral scores indicating that outcome measures were returning toward normal, consistent with our previous study.…”

Diffusion-Derived Magnetic Resonance Imaging Measures of Longitudinal Microstructural Remodeling Induced by Marrow Stromal Cell Therapy after Traumatic Brain Injury

“…Fractional anisotropy (FA), one of the DTI-derived indices, describes the degree of directionality of tissue water diffusion. 23 Because of its ability to capture the alteration of WM integrity, FA is widely used in experimental study 20,24,25 and clinical research 16,21,26 to quantify the extent of structural pathology or therapeutic benefit following brain insult. Although DTI holds value as an excellent imaging modality for identifying axonal injury as well as neuroplasticity that occur in the injured brain 18,27,28 it has a well-known inherent limitation, stemming from the constraints of the tensor model, which prevent DTI from adequately resolving intravoxel fiber crossing.…”