Neuroimaging of subacute brain inflammation and microstructural changes predicts long-term functional outcome after experimental traumatic brain injury

There is currently a lack of prognostic biomarkers to predict the different sequelae following traumatic brain injury (TBI). The present study investigated the hypothesis that subacute neuroinflammation and microstructural changes correlate with chronic TBI deficits. Rats were subjected to Controlled Cortical Impact (CCI) injury, sham surgery or skin incision (naïve). CCI-injured (n=18) and sham-operated rats (n=6) underwent positron emission tomography (PET) imaging with the translocator protein (TSPO) radioligand [18F]PBR111 and diffusion tensor imaging (DTI) in the subacute phase (≤3 weeks post-injury) to quantify inflammation and microstructural alterations. CCI-injured, sham-operated and naïve rats (n=8) underwent behavioural testing in the chronic phase (5.5-10 months post-injury): open field and sucrose preference tests, two one-week video-EEG monitoring periods, pentylenetetrazole seizure susceptibility tests, and a Morris water maze test. In vivo imaging revealed pronounced neuroinflammation, decreased fractional anisotropy and increased diffusivity in perilesional cortex and ipsilesional hippocampus of CCI-injured rats. Behavioural analysis revealed disinhibition, anhedonia, increased seizure susceptibility and impaired learning in CCI-injured rats. Subacute TSPO expression and changes in DTI metrics significantly correlated with several chronic deficits (Pearsons r = 0.50-0.90). Certain specific PET and DTI parameters had good sensitivity and specificity (area under the ROC curve=0.85-1.00) to distinguish between TBI animals with and without particular behavioural deficits. Depending on the investigated behavioural deficit, PET or DTI data alone, or the combination, could very well predict the variability in functional outcome data (adjusted R2=0.54-1.00). Taken together, both TSPO PET and DTI seem promising prognostic biomarkers to predict different chronic TBI sequelae.

Publication year:2018

Authors:International