Spaceflight associated neuro-ocular syndrome (SANS) is an unsolved risk for astronauts on long duration missions. When diagnosed from Frisen grade papilledema on fundoscopy, some 10 of 68 astronauts have exhibited SANS, although related ocular findings are more common (e.g., acquired hyperopia, globe flattening, choroidal folds, retinal fiber nerve layer thickening). Unexpectedly, SANS signs do not always spontaneously resolve upon return to Earth gravity. While the cause of SANS is unknown, the hyperopia, globe flattening, and choroidal folds—coupled with typically normal or slightly elevated intra-ocular pressure (IOP)—suggests that intracranial pressure (ICP) may be elevated as compared to average Earth levels. Various pathophysiological mechanisms have been proposed for SANS, with a particular suspicion regarding cephalad fluid shifts.
Most hypotheses regarding SANS involve headward fluid shifts as a factor, and various proposed SANS countermeasures (CMs)—including lower-body negative pressure (LBNP), veno-constrictive thigh cuffs (VTC), inspiratory resistance threshold devices (ITD), and artificial gravity (AG) all involve “mechanical” redistribution of body fluids away from the head. Understanding the relative benefits of each CM calls for assessments of perfusion and fluid flow into, within, and out of the cranium not only for potentially assessing and monitoring SANS, but also to help quantify and compare the effect sizes of various CMs.
SANS-CM Study at German Aerospace Center's (DLR) Envihab Facility
To address the lack of SANS CMs, NASA has negotiated a plan with the German Aerospace Center’s :envihab facility to conduct 30-day head-down tilt (HDT) bedrest studies—the SANS-CM study. This effort has evolved to include 6 study arms:
1. 6o HDT bedrest alone (Reference); 2. 6o HDT bedrest plus two 3-hour periods seated upright (Seated CM); 3. 6o HDT bedrest plus 16 hours seated control (Control); 4. 6o HDT bedrest plus two 3-hour periods of LBNP (LBNP CM); 5. 6o HDT bedrest plus a B-complex vitamin supplement (Vit-B CM); 6. 6o HDT bedrest plus two ~1-hour periods of exercise plus VTC (Exercise CM).
Each arm will consist of n=12 subjects, and different investigators will be involved in different portions of the overall SANS-CM study.
BRAIN-SANS Contribution.This BRAIN-SANS project seeks to provide a wide range of brain-related measures for all subjects in all study arms. These include changes in (i) intracranial pressure (ICP), (ii) blood flow in/out of the brain, (iii) cerebral blood flow, (iv) brain perfusion and oxygenation, (v) blood distribution along the body axis, (vi) intracranial pulsatility, (vii) sagittal sinus imaging of potential, (viii) intracranial water concentration, (ix) functional brain activation, (x) electrical brain activity, as well as (xi) cognitive performance data (Cognition). We also plan to compare these measures with measures from other groups including ocular measures, mood and sleep, 1-carbon single nucleotide polymorphisms, and MRI.
ACHIEVEMENTS IN YEAR 1
By the end of the 1st year of this project, we will have completed the following major tasks:
Institutional Review Board (IRB) approval: Massachusetts General Hospital (MGH) granted Cede Review status to NASA on July 3, 2020. The NASA IRB granted full approval on Dec 8, 2020.
Integration of BRAIN-SANS with all study arms and other investigators: This involved increasing the scope from 3 study arms to 6 study arms, coordinating with other SANS-CM investigators for data sharing, and adjusting our measurement timeline based on feasibility, hardware, and personnel constraints.
Completion of Aim 1, development of the toolbox for multi-modal brain assessment: We assembled the required hardware and completed the needed customizations, configuration, and donning plans to achieve our measurement goals (see BRAIN-SANS Contribution, above). These measurements will be made during both rest and pre/during/post-countermeasure deployment.
Experimental preparations: We have all hardware ready for shipping to DLR, when that is warranted based on COVID-19 restrictions. We have assembled manuals for all devices to be used. We have also developed detailed protocols for DLR :envihab personnel to facilitate making the BRAIN-SANS measurements, as well as all training materials for virtual training of DLR personnel. During the training process, we expect that further optimizations will be made to the experimental protocol details—adding, removing, or modifying procedural steps to ensure more accurate, reliable, and thorough data collection from the study. This process will also continue into the early part of grant year 2 as the first SANS-CM Mission approaches. Ideally, further optimization can be completed in-person in the July-August 2021 timeframe.
Despite challenges bought on by COVID-19 since the beginning of our funding, we have met all deadlines and achieved all required integration. We are thus on-track to conduct our component of the SANS-CM study as soon as it can feasibly be initiated.