Clusters of Low (18)F-Fluorodeoxyglucose Uptake Voxels in Combat Veterans with Traumatic Brain Injury and Post-Traumatic Stress Disorder

Individuals with mild traumatic brain injury (TBI) show diminished metabolic activity when studied with positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG). Since blast injury may not be localized in the same specific anatomical areas in every patient or may be diffuse, significance probability mapping may be vulnerable to false-negative detection of abnormalities. To address this problem, we used an anatomically independent measure to assess PET scans: increased numbers of contiguous voxels that are 2 standard deviations below values found in an uninjured control group. We examined this in three age-matched groups of male patients: 16 veterans with a history of mild TBI, 17 veterans with both mild TBI and post-traumatic stress disorder (PTSD), and 15 veterans without either condition. After FDG administration, subjects performed a modified version of the California Verbal Learning Task. Clusters of low uptake voxels were identified by computing the mean and standard deviation for each voxel in the healthy combat veteran group and then determining the voxel-based z-score for the patient groups. Abnormal clusters were defined as those that contained contiguous voxels with a z-score <-2. Patients with mild TBI alone and patients with TBI+PTSD had larger clusters of low uptake voxels, and cluster size significantly differentiated the mild TBI groups from combat controls. Clusters were more irregular in shape in patients, and patients also had a larger number of low-activity voxels throughout the brain. In mild TBI and TBI+PTSD patients, but not healthy subjects, cluster volume was significantly correlated with verbal learning during FDG uptake.