Differential recovery of behavioral status and brain function assessed with functional magnetic resonance imaging after mild traumatic brain injury in the rat

OBJECTIVE: The relationship between cerebral integrity, recovery of brain function, and neurologic status after mild traumatic brain injury is incompletely characterized. DESIGN: Prospective and randomized study in rodents. SETTING: University laboratory. SUBJECTS: Male Wistar rats (290-310 g). INTERVENTIONS: In rats, quantitative diffusion weighted imaging (DWI), perfusion weighted imaging (PWI), T2-weighted imaging (T2WI), and functional magnetic resonance imaging (fMRI) were performed up to 21 days after weight-induced, closed-head, mild traumatic brain injury (MTBI, n = 6) or sham operation (n = 6). Pixel-by-pixel analysis and region of interest analysis were used to evaluate structural (apparent diffusion coefficient [ADC] and basal cerebral blood flow [bCBF]) and functional magnetic resonance signal changes within the brain, respectively. Quantitative fMRI signal changes were correlated with behavioral measures. MEASUREMENTS AND MAIN RESULTS: Despite normal appearing DWI and T2WI findings following MTBI, persistent hypoperfusion developed that was not associated with cytotoxic edema. In contrast, the ADC was significantly increased by approximately 5% at 1 and 7 days post-MTBI. Post-MTBI fMRI responses to hypercapnia and forepaw stimulation were significantly impaired and showed a differential recovery rate between and within investigated region of interests. Significant dysfunction in forepaw placement test persisted up to day 1 and correlated significantly with fMRI signal changes in the primary somatosensory and motor cortices. CONCLUSIONS: MTBI produced distinct changes on multimodal MRI and behavioral variables acutely and chronically. Following MTBI, fMRI and ADC-bCBF pixel-by-pixel analysis identified subtle structural and functional alterations in the brain that appeared completely normal on conventional DWI and T2WI after concussion injury. The former techniques may therefore provide great potential for understanding mild traumatic brain injury, identifying mechanisms underlying recovery, and investigating specific interventions to enhance functional outcome