White Matter Integrity in High-Altitude Pilots Exposed to Hypobaria

Abstract

Introduction Nonhypoxic hypobaric (low atmospheric pressure) occupational exposure, such as experienced by U.S. Air Force U-2 pilots and safety personnel operating inside altitude chambers, is associated with increased subcortical white matter hyperintensity (WMH) burden. The pathophysiological mechanisms underlying this discrete WMH change remain unknown. The objectives of this study were to demonstrate that occupational exposure to nonhypoxic hypobaria is associated with altered white matter integrity as quantified by fractional anisotropy (FA) measured using diffusion tensor imaging and relate these findings to WMH burden and neurocognitive ability. Methods There were 102 U-2 pilots and 114 age- and gender-controlled, health-matched controls who underwent magnetic resonance imaging. All pilots performed neurocognitive assessment. Whole-brain and tract-wise average FA values were compared between pilots and controls, followed by comparison within pilots separated into high and low WMH burden groups. Neurocognitive measurements were used to help interpret group difference in FA values. Results Pilots had significantly lower average FA values than controls (0.489/0.500, respectively). Regionally, pilots had higher FA values in the fronto-occipital tract where FA values positively correlated with visual-spatial performance scores (0.603/0.586, respectively). There was a trend for high burden pilots to have lower FA values than low burden pilots. Discussion Nonhypoxic hypobaric exposure is associated with significantly lower average FA in young, healthy U-2 pilots. This suggests that recurrent hypobaric exposure causes diffuse axonal injury in addition to focal white matter changes.

Acute and Chronic Effects of Hypobaric Exposure upon the Brain

“…Calibration MRI data was performed in 46 patients (CAL) on both the RII and WHASC scanners for the cross comparison and analysis of advanced imaging sequences such as diffusion imaging [5]. The calibration for the average FA values in subjects imaged on both scanners showed excellent correlation (r = 0.85), with coefficients of variation were similar to what has been previously reported [56,57].…”

“…WMHs are regions of accumulation of extra-cellular water due to focal degradation of the myelin sheath [3], and the volume of WMHs is a non-specific marker of cerebral integrity sensitive to multiple etiologies [4]. Repetitive normoxic hypobaric exposure is associated with a decrease in axonal integrity as quantified by global decrease in Fractional Anisotropy (FA) using diffusion tensor imaging (DTI) technique in magnetic resonance imaging (MRI) [5].…”

White matter and hypoxic hypobaria in humans

“…High angular resolution diffusion imaging (HARDI) was utilized for DTI and fractional anisotropy (FA) as previously reported (McGuire et al, ). Briefly, DTI data were collected using a single‐shot echo‐planar, single refocusing spin‐echo, T2‐weighted sequence with a spatial resolution of 1.7 × 1.7 × 3.0 mm with sequence parameters of TE/TR = 87/8,000 ms, field of view (FOV) = 200 mm, axial slice orientation with 50 slices and no gaps, 64 isotropically distributed diffusion‐weighted directions, two diffusion weighting values ( b = 0 and 700 s/mm 2 ), and five b = 0 images.…”

Physiologic Challenges to Pilots of Modern High Performance Aircraft

“…Specifically U2 pilots and altitude chamber staff have white matter changes which are seen on MRI [26,27]. These changes have been linked to diffuse axonal injury [28] and those with a higher burden of white matter changes score lower on neurocognitive tests when compared to other pilots [29]. All these changes were linked to hypobaria without hypoxia, thus it seems low pressure itself may be a risk for permanent changes in the brain which can lead to subtle cognitive decline.…”