RT Journal Article SR Electronic T1 FDG-PET for individualized longitudinal assessment of brain alterations after repetitive mild blast injury in Veterans JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1482 OP 1482 VO 60 IS supplement 1 A1 Donna Cross A1 Satoshi Minoshima A1 Garth Terry A1 David Cook A1 James Meabon A1 Kathleen Pagulayan A1 Murray Raskind A1 Elaine Peskind YR 2019 UL http://jnm.snmjournals.org/content/60/supplement_1/1482.abstract AB 1482Objectives: Repetitive mild traumatic brain injuries (mTBIs) may lead to an increased risk of future neurodegeneration, but such processes have not been investigated systematically. The goal of this research is to characterize longitudinal alterations in regional neuronal activity among Veterans with previous repeat blast mTBIs using FDG PET. Methods: Positron emission tomography with [18F]-fluorodeoxyglucose (FDG PET) was used to assess brain metabolism in 10 Veterans with repetitive mTBI (age 38.0±10.8, range 25-59 yrs) and 4 deployed controls (DC) with no blast exposure (age 35.8±7.7, range 28-45 yrs). Community controls (n=9, 28.0±8.1, range 20-45 yrs) were used as reference normal data. Each subject received two FDG-PET scans with a mean scan interval of 3.3±0.8 and 3.0±0.29 years for the DC and mTBI groups, respectively that was not significantly different (t[12]=0.44, n.s.). Images were anatomically standardized, normalized to global uptake and compared to the normal database to produce individual Z-score maps where higher Z values represent hypometabolic pixels (HP) (3D-SSP, U. UTAH). A custom algorithm was applied to the individual Z-score maps for each paired image set that counted the number pixels of 26 brain regions with a Z-score above a set threshold (Z>1.64). Longitudinal changes in number of HPs exceeding the threshold within each region as well as total global (GBL) and total cortex (CTX) were counted and within and between group differences were assessed statistically. To overcome challenges from heterogeneous brain reorganization and differences in injury patterns, we calculated a ratio of the number of regions (RR) with decreased HPs divided by the number of regions indicating increased HPs as a very general assessment of decline (<1.0) or recovery (>1.0). Results: Groupwise comparisons between mTBI and DC of scan 1, scan 2, and scan 2-1 differences showed scattered regional decreases in mTBI that did not achieve statistical significance after Bonferonni corrections for multiple comparisons. No between or within group differences were found among GBL or CTX groups, indicating that variability of individualized longitudinal changes (see figure) were obscuring group differences. One of four DC subjects had RR<1.0 (RR=0.64) (25%) indicating increases in hypometabolic pixels and 3 subjects RR>1.0 (range 1.67 - 2.75) indicated improvement (DC RR=1.42±0.86, mn+sd). In mTBI, 8/10 subjects (80%) had RR<1.0 (range 0.26-0.75) indicating decline (increased HPs) and 2 subjects RR>1.0 indicating FDG-PET improvement (RR=7 and 1.67 respectively, mTBI group RR=0.74±2.03). A Chi-square analysis indicated there was a significant difference between the number of subjects declining the mTBI versus DC group (p&#8804;0.05). Conclusions: Although groupwise changes of longitudinal FDG-PET scans were not found, a ratio of regions showing reduced number of hypometabolic pixels compared to increased hypometabolic pixels was able to differentiate individuals that may be declining from those that may be recovering from mTBI. These results indicate that groupwise assessment in longitudinal imaging follow up may be inadequate to detect such individualized changes after repetitive mTBI. Comparison of individual patterns with clinical data is ongoing. Although currently no treatments exist to mitigate poor outcome after repetitive mTBI, it is important for future clinical trials to have an objective means to identify patients that may benefit from specific therapeutic interventions.