Detection of Regional Neurometabolic Differences in Individual TBI Subjects After tDCS Therapy

1532 Objectives: FDG-PET imaging is a sensitive, non-invasive tool for evaluating neurometabolic changes in mild traumatic brain injury (TBI) patients. Previous FDG-PET studies of mild TBI have demonstrated significant alterations in brain metabolism in the absence of any visible brain lesions on structural imaging (CT/MRI). In this pilot study, we used FDG-PET in combination with atlas-based image analysis to identify glucose uptake differences in individual TBI subjects following transcranial direct current stimulation (tDCS) therapy. Methods: Baseline and followup FDG-PET scans were obtained prospectively in six subjects with a history of mild to moderate traumatic brain injury (mmTBI) and chronic cognitive post-concussive symptoms. In between scans, subjects underwent left dorsolateral prefrontal anodal tDCS with active (n=3) or sham (n=3) stimulation concurrent with cognitive training for up to ten consecutive weekdays. Subject FDG-PET data were acquired in list mode for 60mins on a Biograph mCT (Siemens Medical Systems) using a brain time-of-flight (TOF) acquisition and reconstructed as a single static frame (45-60mins) with CT-based attenuation correction. Atlas-based analysis of static PET data was performed using NeuroQ version 3.8 (Syntermed Inc). Static PET reconstructions were normalized to the entire atlas comprised of gray matter regions (whole-brain normalization). FDG-PET scans at baseline and followup were each compared to the NeuroQ control database (50 subjects, age range 20-89) to determine regional z-scores. A z-score outside 2σ at baseline or followup indicated a statistically significant difference. Regions with z-scores outside 2σ at both baseline and followup indicated no difference between timepoints and were excluded. Results: Significant regional neurometabolic differences were detected for all subjects, with z-scores ranging from 2.35 (most hypermetabolic) to -2.18 (most hypometabolic). However, there was marked regional heterogeneity at the individual subject level, with the vermis being the only region detected in more than one subject. All of the regions detected in actively treated subjects demonstrated an increase in neurometabolism directionality from baseline to followup; this includes regions that were hypometabolic at baseline and normal at followup (left Broca’s region and right parietotemporal cortex), in addition to regions that were normal at baseline and hypermetabolic at followup (left inferior frontal cortex and vermis). In sham subjects, the directionality was variable, with one subject demonstrating a decrease in significant regions and two other subjects demonstrating an increase. Conclusions: FDG-PET imaging with atlas-based analysis is useful for detecting regional neurometabolic differences in individual subjects following tDCS therapy. The significant regions detected using NeuroQ included substructures of the cortex and cerebellum. Regional FDG uptake in mmTBI subjects is highly heterogeneous at the single-subject level and likely reflects the heterogeneous nature of the injury and recovery. Interestingly, a trend of regional activation was observed in tDCS-treated but not in sham-treated subjects. Future work will include the comparison of subject data to a site-specific FDG-PET database of normal controls and correlation of imaging findings to measures of cognitive control.