A PROPOSED MECHANISM FOR HYPOBARIC-INDUCED NEURONAL INJURY: A SWINE MODEL (P4.068)

Objective: Develop an animal model for axonal cerebral injury following non-hypoxic hypobaric exposure utilizing magnetic resonance diffusion tensor imaging, Q-space and advanced diffusion kurtosis imaging. Background: Human exposure to non-hypoxic hypobaria is associated with increased white matter hyperintensities, diffuse degradation of axonal integrity, and decrements in neurocognitive processing. The mechanism by which this occurs is unknown. We hypothesized that MR diffusion could offer insight into the pathophysiology of hypobaric-induced cerebral injury and we developed a swine model to test this theory. Design/Methods: Miniature pigs (Sus scrofa domestica) were repetitively exposed to non-hypoxic hypobaria at 30,000 feet while controls remained at 5,000 feet altitude. MRI was obtained at baseline, immediately post-exposure and 4 weeks post-exposure. Advanced diffusion quantification was used to include kurtosis anisotropy, multi-b-value diffusion (Q-space), and fractional anisotropy (FA). 2-tailed t-tests were used for individual and group comparisons. Results: Perfusion-diffusion index (PDI) and mean kurtosis anisotropy revealed an increase in unrestricted water immediately after repetitive high-altitude exposures. In addition, age-adjusted average FA significantly decreased at 4 weeks post-exposure in the high-altitude group compared to controls (p Conclusions: PDI and kurtosis demonstrate an increase in unrestricted water after repetitive hypobaric exposure, consistent with injury. The significant decrease in FA at 4 weeks suggests degradation of axonal integrity. This replicates similar MRI findings in humans. The study provides evidence that repetitive hypobaric exposure incites axonal damage, and that swine may be a feasible animal model with which to improve our understanding of injury mechanisms and potentially test interventions that could reduce hypobaric neuronal injury in the future. Study Supported by: Research is sponsored by USAF/SG, 711HPW, 59MDW, and JPC-5 Disclosure: Dr. Peralta has nothing to disclose. Dr. Sladky has nothing to disclose. Dr. Sherman has nothing to disclose. Dr. McGuire has nothing to disclose.