Abstract
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Objectives: Traumatic Brain Injury (TBI) is a complex phenomenon caused by an external mechanical force. It is a significant source of morbidity and mortality throughout the world. The development of preclinical models of TBI and ability to perform neuroimaging in these models is critical in identifying the pathophysiological changes that occur after TBI. The objective of this study was to characterize a primary overpressure blast injury in rat brain using FDG PET imaging.
Methods: Adult male Sprague Dawley rats (n=12) were imaged at 3-time points (prior to injury, baseline; 1-3 hours post injury, day 0; and one-week post injury, day 7). PET/CT images were acquired using an Inveon multimodality preclinical scanner (Siemens Medical Solutions, Erlangen, Germany). The rats were divided into two groups, sham (n=6) and blast (n=6). The rats were exposed to a blast using a custom-built advanced blast simulator (Ora Inc, Fredericksburg, VA). For PET/CT imaging, Anesthetized animals were injected with [18F] FDG (0.966 ± 0.05 mCi) into the lateral tail vein. After injection, animals were returned to a separate cage (on a heating pad at 37°C) without food and water for conscious uptake (30 minutes). The total uptake time before PET imaging was 45 minutes (30 minutes awake and 15 minutes anesthetized). Physiologic monitoring during imaging included measurements of temperature, respiration rate, heart rate and oxygen saturation. A 30-minute static PET scan was acquired in list mode (350-650keV, 3.483 ns) with an axial field of view of 12.7 cm. A brief CT scan (3 bed in ‘rat mode’, 500uA, 80kVp) was acquired followed by PET scans for anatomical localization, and attenuation and scatter correction. The PET data were reconstructed as a single static frame with OSEM3D/MAP algorithm and corrected for scatter and attenuation. The CT images were reconstructed using Feldkamp algorithm, downsampled and beam hardening and HU corrections applied. The reconstructed PET/CT data were processed and analyzed using Vivoquant Software version 3.0 (inviCRO, Boston, MA). The PET data were registered to 13 regions from the rat brain atlas by way of CT using an automatic algorithm. The data analysis was performed using a semi quantitative
Methods: Standardized Uptake Value (SUV - activity concentration in a specific region normalized to the total injected activity and body weight) normalized to the whole brain (SUVw) was analyzed. All statistical analyses were conducted using Graphpad Prism software version 7.01. Result: Volume-of-Interest analysis (Vivoquant atlas) showed statistically significant differences in regional FDG uptake. 1. Amygdala, Olfactory, and Corpus Callosum all showed higher FDG uptake in Blast group, both at day 0 and day 7 when compared to the Sham group (Two-way Repeated Measures ANOVA, Sidak’s multiple comparisons test). 2. The Midbrain showed lower FDG uptake at day 0 in Blast group when compared to the Sham group (Two-way Repeated Measures ANOVA, Sidak’s multiple comparisons test). Conclusion: The primary blast wave caused an acute increase in FDG uptake in the olfactory and amygdala, and a decrease in uptake in the midbrain. These data suggest that primary blast injury model may be useful for isolating neurological changes after blast using FDG PET. Research Support: The work was supported by the Department of Defense through the Center for Neuroscience and Regenerative Medicine and the Henry M. Jackson Foundation for the Advancement of Military Medicine. References: 1. McCabe JT et. al. (2010). Animal models for the study of military-related, blast-induced traumatic brain injury. BSEC. 2. Zald DH et. al. (1997). Emotion, olfaction, and the human amygdala: Amygdala activation during aversive olfactory stimulation. Proc. Natl. Acad. Sci. 3. Soudry Y. et. al. (2011). Olfactory system and emotion: common substrates. European Annals of Otorhinolaryngology, Head and Neck diseases.