Recent findings of elevated white matter hyperintensities (WMHs) in NASA crewmembers are concerning. It is not clear whether these white matter irregularities arise due to spaceflight, extravehicular activity, or some aspect of preflight training such as neutral buoyancy training. Dr. Rachael Seidler is currently conducting a NASA funded flight study of brain and behavioral changes that occur in space; she has recently completed a complementary bed rest study under NSBRI support. Some of the crewmembers enrolled in the flight study are repeat flyers, but several are first timers. Thus she will be able to examine crewmember preflight white matter integrity in relation to bed rest and control subjects to identify whether high white matter burden is evident even prior to flight. Moreover, with support from the current application, she will be able to access diffusion weighted images from the LSAH archives to analyze pre to post flight changes in white matter integrity in comparison to her recently collected control group data (acquired on the same MRI scanner at UTMB Victory Lakes). It is important to understand the source of white matter changes in crewmembers, as WMHs typically increase with normal aging and are associated with cognitive declines.
Evaluation of Brain White Matter Integrity in NASA Crewmembers: Comparisons with Controls, Changes with Flight, and Behavioral Consequences
Rachael D. Seidler, Ph.D.
University of Michigan
Recent reports of elevated brain white matter hyperintensity (WMH) counts and volume in astronauts are concerning. WMHs or ‘white matter lesions’ are caused by cerebral small vessel disease (microangiopathy) that results in ischemia through vascular stenosis. They typically increase with normal aging and are associated with cognitive and motor declines, raising the possibility that spaceflight, or some aspect of preflight training, is linked to accelerated brain aging. It has been reported that U-2 high altitude aircraft pilots, exposed to hypobaria, exhibit WMHs that are several hundred percent above normal in both count and volume. Astronauts have been reported to exhibit WMHs that are approximately twice that of U-2 pilots. One possible mechanism could be extravehicular activity, but this does not appear to be a mediating factor at this point. Since only post flight data have been examined, it is not clear whether elevated WMHs in astronauts stem from some aspect of spaceflight itself or if they rather develop during training. One component of astronaut training is underwater missions in the Neutral Bouyancy Laboratory. Several studies suggest that repeated exposure to recreational as well as professional diving affects the microvasculature of the brain. These adverse effects are thought to result from the migration of inert gas bubbles in the venous to the arterial system, leading to cerebral and cerebellar arterial inert gas embolisms that can cause white matter lesions (Knauth, 2008; Knauth et al., 1997). In addition, the use of oxygen-enriched breathing gas (commonly called Nitrox) poses the risk of central nervous system oxygen toxicity. All astronaut divers use Nitrox to reduce the incidence of the bends with long training sessions. Thus, frequent and long exposure diving in combination with the use of Nitrox could potentially impact white matter in the brain through the vascular system or other mechanisms. It is likely that negative effects would be related to decompression sickness, with Nitrox potentially decreasing risks. It is therefore important to compare white matter integrity imaged in crewmembers pre-flight to controls, as well as to examine pre- to post- flight changes, and to examine any associations with cognitive and sensorimotor function.
We propose to address this important issue through the following aims:
- We will access diffusion weighted images from the LSAH that have been collected on NASA astronauts pre and post flight over the past eight years. We will compare pre-flight measures of white matter integrity to data that we have already collected in 16 controls, and we will quantify and localize any changes in white matter integrity from pre to post flight. Some of these crewmembers also have pre and post flight FLAIR MRI scans so we could quantify WMHs in these individuals and examine how they relate to diffusion weighted metrics.
- We will test for correlations between white matter integrity changes in these crewmembers and behavioral changes in posture control, locomotion, and cognition.
Given that white matter hyperintensities increase with normal aging and are associated with sensorimotor and cognitive declines, it is important to better understand how environmental conditions predispose one to elevated numbers.