Amide Proton Transfer-Weighted Magnetic Resonance Imaging for Detecting Severity and Predicting Outcome after Traumatic Brain Injury in Rats

After traumatic brain injury (TBI), early assessment of secondary injury severity is critically important for estimating prognosis and treatment stratification. Currently, secondary injury severity is difficult to estimate. The objective of this study was to investigate the capacity of non-invasive amide proton transfer-weighted (APTw) magnetic resonance imaging (MRI) techniques to assess TBI injury in different brain regions and predict long-term neurobehavior outcomes. Fifty-five male and female rats were subjected to a controlled cortical impact with one of three different impactor depths to produce different degrees of TBI. Multi-parameter MRI data were acquired on a 4.7-Tesla scanner at 1 h, 1 day, and 3 days. Immunofluorescence staining was used to detect activated microglia at 3 days, and neurobehavioral tests were performed to assess long-term outcomes after 28 days. The APTw signal in the injury core at 1 day correlated with deficits in sensorimotor function, the sucrose preference test (a test for anhedonia), and spatial memory function on the Barnes maze. The APTw signal in the perilesion ipsilateral cortex gradually increased after TBI, and the value at 3 days correlated with microglia density at 3 days and with spatial memory decline and anhedonia at 28 days. The correlation between APTw and activated microglia was also observed in the ipsilateral thalamus, and its correlation to memory deficit and depression was evident in other ipsilateral sites. These results suggest that APTw imaging can be used for detecting secondary injury and as a potential predictor of long-term outcomes from TBI.