Glutamate excitoxicity plays a crucial role in the pathophysiology of traumatic brain injury (TBI) through the initiation of secondary injuries. Glutamate chemical exchange saturation transfer (GluCEST) MRI is a newly developed technique to noninvasively image glutamate in vivo with high sensitivity and spatial resolution. The aim of the present study was to use a rat model of TBI to map changes in brain glutamate distribution and explore the capability of GluCEST imaging for detecting secondary injuries. Sequential GluCEST imaging scans were performed in adult male Sprague-Dawley rats before TBI and at 1, 3, 7, and 14 days after TBI. GluCEST% increased and peaked on day 1 after TBI in the core lesion of injured cortex and peaked on day 3 in the ipsilateral hippocampus, as compared to baseline and controls. GluCEST% gradually declined to baseline by day 14 after TBI. A negative correlation between the GluCEST% of the ipsilateral hippocampus on day 3 and the time in the correct quadrant was observed in injured rats. Immunolabeling for glial fibrillary acidic protein showed significant astrocyte activation in the ipsilateral hippocampus of TBI rats. IL-6 and TNF-α in the core lesion peaked on day 1 postinjury, while those in the ipsilateral hippocampus peaked on day 3. These subsequently gradually declined to sham levels by day 14. It was concluded that GluCEST imaging has potential to be a novel neuroimaging approach for predicting cognitive outcome and to better understand neuroinflammation following TBI.
Keywords: MRI; chemical exchange saturation transfer; glutamate; neuroinflammation; traumatic brain injury.