Alteration of FDG uptake following mTBI by Performing Novel Object Recognition during Uptake

1632 Objectives: Traumatic Brain Injury (TBI) affects approximately 1.5 million people in the United States, of which 80% are considered as mild TBI (mTBI). The functional metabolic deficits observed following mTBI are associated with changes in cognitive performance. The objective of this pilot study was to investigate the effect of addition of cognitive testing during FDG uptake on acute regional metabolic changes in the rat brain after mild lateral fluid percussion (mLFP) injury. Methods: Adult male Sprague Dawley rats (n=9) were used in this study. The PET scans were acquired prior to and after a mLFP, during which a 5 mm craniotomy was performed over the left parietal cortex midway between lambda and bregma and 2.5 mm from the vertex. The fluid percussion device (VCU Health System Custom Design and Fabrication Model 01-B) was attached via a short piece of tubing to a plastic female luer lock cemented over the craniotomy. An impact with an estimated pressure of 1.5 atm was achieved by dropping a pendulum onto the water tube from an angle of 10-15°. For PET/CT imaging, animals were anesthetized with isoflurane for tail vein injection (1.5 - 2.0 mCi FDG). After injection, the animals were returned to a separate box for conscious uptake and cognitive testing (Novel Object Recognition, NOR; n=5) or non-directed exploration (n=4) during FDG uptake. During the uptake the box was placed on a heating pad maintained at 37°C. The total uptake time before PET imaging was 45 minutes (30 minutes awake and 15 minutes anesthetized). The imaging was performed using a Siemens Inveon preclinical scanner (Erlangen, Germany). The PET scans were acquired for 30 minutes followed by a brief CT acquisition for anatomical localization and attenuation and scatter correction. The reconstructed PET/CT data were processed and analyzed using Vivoquant Software version 3.0 (inviCRO, Boston MA). The PET data were registered to a 26 region rat brain atlas by way of CT using an automatic algorithm. The data analysis was performed using a semi quantitative Methods: Standardized Uptake Objectives: alue (SUV - activity concentration in a specific region normalized to the total injected activity and body weight) normalized to the whole brain (SUVw). All statistical analyses were conducted using GraphPad Prism program version 7.0 (GraphPad Software, San Diego, CA). Results: 1. No significant metabolic changes in the ipsilateral hippocampus at pre injury and post injury scans were observed between the Novel and No Novel Object group. 2. Significant metabolic changes were observed both at pre injury and post injury scans in contralateral hippocampus between the Novel and No Novel Object group. 3. The fold change between pre injury and post injury scans was greater in the No Novel Object group than in the Novel Object group. Conclusions: Our findings demonstrate that metabolic changes due to mLFP can be evaluated using [18F] FDG imaging. Cognitive testing during FDG uptake plays an interesting role in the brain uptake pattern, showing a suppression of the effect of injury, particularly in the contralateral hippocampus. These data suggest that cognitive testing alters FDG uptake and affects injury related measurements. References: 1. Frumberg et. al. (2007, Brain Res. 1144: 209-218) 2. Ennaceur A. & Delacour J. (1988, Behav. Brain Res.31, 47-59 ) 3. Selwyn et. al. (2013, J. of Neurotrauma 30(23): 1943-1953) Research Support: This project is supported by funding from NIH/NINDS, and CNRM and HJF.