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NASA NTRS2009

NASA Tech Briefs, May 2009

Topics covered include: Valve-"Health"-Monitoring System; Microstrip Antenna for Remote Sensing of Soil Moisture and Sea Surface Salinity; Biomedical Wireless Ambulatory Crew Monitor; Wireless Avionics Packet to Support Fault Tolerance for Flight Applications; Aerobot Autonomy Architecture; Submillimeter Confocal Imaging Active Module; Traveling-Wave Maser for 32 GHz; System Synchronizes Recordings from Separated Video Cameras; Piecewise-Planar Parabolic Reflectarray Antenna; Reducing Interference in ATC Voice Communication; EOS MLS Level 1B Data Processing, Version 2.2; Auto-Generated Semantic Processing Services; Geospatial Authentication; Maneuver Automation Software; Event Driven Messaging with Role-Based Subscriptions; Estimating Relative Positions of Outer-Space Structures; Fabricating PFPE Membranes for Capillary Electrophoresis; Linear Actuator Has Long Stroke and High Resolution; Installing a Test Tap on a Metal Battery Case; Fabricating PFPE Membranes for Microfluidic Valves and Pumps; Room-Temperature-Cured Copolymers for Lithium Battery Gel Electrolytes; Catalysts for Efficient Production of Carbon Nanotubes; Amorphous Silk Fibroin Membranes for Separation of CO2; "Zero-Mass" Noninvasive Pressure Transducers; Radial-Electric-Field Piezoelectric Diaphragm Pumps; Ejector-Enhanced, Pulsed, Pressure-Gain Combustor; Suppressing Ghost Diffraction in E-Beam-Written Gratings; Target-Tracking Camera for a Metrology System; Polarimetric Imaging using Two Photoelastic Modulators; Miniature Wide-Angle Lens for Small-Pixel Electronic Camera; Modal Filters for Infrared Interferometry; Mo(3)Sb(7-x)Te(x) for Thermoelectric Power Generation; Two-Dimensional Quantum Model of a Nanotransistor; Scanning Miniature Microscopes without Lenses; Manipulating Neutral Atoms in Chip-Based Magnetic Traps; Expansion Compression Contacts for Thermoelectric Legs; Processing Electromyographic Signals to Recognize Words; Physical Principle for Generation of Randomness; DSN Beowulf Cluster-Based VLBI Correlator; Hybrid NN/SVM Computational System for Optimizing Designs; Criteria for Modeling in LES of Multicomponent Fuel Flow; Computerized Machine for Cutting Space Shuttle Thermal Tiles; Orbiting Depot and Reusable Lander for Lunar Transportation; FPGA-Based Networked Phasemeter for a Heterodyne Interferometer; Aquarius Digital Processing Unit; Three-Dimensional Optical Coherence Tomography; Benchtop Antigen Detection Technique using Nanofiltration and Fluorescent Dyes; Isolation of Precursor Cells from Waste Solid Fat Tissue; Identification of Bacteria and Determination of Biological Indicators; Further Development of Scaffolds for Regeneration of Nerves; Chemically Assisted Photocatalytic Oxidation System; Use of Atomic Oxygen for Increased Water Contact Angles of Various Polymers for Biomedical Applications; Crashworthy Seats Would Afford Superior Protection; Open-Access, Low-Magnetic-Field MRI System for Lung Research; Microfluidic Mixing Technology for a Universal Health Sensor; Microfluidic Extraction of Biomarkers using Water as Solvent; Microwell Arrays for Studying Many Individual Cells; Droplet-Based Production of Liposomes; and Identifying and Inactivating Bacterial Spores

Source record↗
NASA NTRS2009

Non-invasive in vivo measurement of macular carotenoids

A non-invasive in vivo method for assessing macular carotenoids includes performing Optical Coherence Tomography (OCT) on a retina of a subject. A spatial representation of carotenoid levels in the macula based on data from the OCT of the retina can be generated.

Lambert, James L.↗
NASA NTRS2010

Space Flight-Induced Intracranial Hypertension: An Ophthalmic Review

Background: Although physiologic and pathologic changes associated with microgravity exposure have been studied extensively, the effect of this environment on the eye is largely unknown. Over the last several years, NASA s Space Medicine Division has documented astronauts presenting with varying degrees of disc edema, globe flattening, choroidal folds, cotton wool spots, and hyperopic shifts after long-duration space flight. Methods: Before and after long-duration space flight, six astronauts underwent complete eye examinations to include cycloplegic and/or manifest refraction and fundus photography. Five of these astronauts had Optical Coherence Tomography (OCT) and Magnetic Resonance Imaging (MRI) performed following their missions. Results: Following exposure to space flight of approximately 6-months duration, six astronauts had neuro-ophthalmic findings. These consisted of disc edema in four astronauts, globe flattening in four astronauts, choroidal folds in four astronauts, cotton wool spots in three astronauts, nerve fiber layer thickening by OCT in five astronauts, and decreased near vision in five astronauts. Four of the astronauts with near vision complaints had a hyperopic shift equal to or greater than + 0.50D between pre- and post-mission spherical equivalent refraction in one or both eyes (range +0.50D to +1.50D). These same four had globe flattening by MRI. Conclusions: The findings we describe may have resulted from a rise in intracranial pressure caused by microgravity fluid shifts, and could represent parts of a spectrum of ocular and cerebral responses to extended microgravity.

Gibson, Charles Robert↗
NASA NTRS2012

Long Duration Head-Down Tilt Bed Rest Studies: Safety Considerations Regarding Vision Health

Visual symptoms reported in astronauts returning from long duration missions in low Earth orbit, including hyperopic shift, choroidal folds, globe flattening and papilledema, are thought to be related to fluid shifts within the body due to microgravity exposure. Because of this possible relation to fluid shifts, safety considerations have been raised regarding the ocular health of head-down tilt (HDT) bed rest subjects. HDT is a widely used ground ]based analog that simulates physiological changes of spaceflight, including fluid shifts. Thus, vision monitoring has been performed in bed rest subjects in order to evaluate the safety of HDT with respect to vision health. Here we report ocular outcomes in 9 healthy subjects (age range: 27-48 years; Male/Female ratio: 8/1) completing bed rest Campaign 11, an integrated, multidisciplinary 70-day 6 degrees HDT bed rest study. Vision examinations were performed on a weekly basis, and consisted of office-based (2 pre- and 2 post-bed rest) and in-bed testing. The experimental design was a repeated measures design, with measurements for both eyes taken for each subject at each planned time point. Findings for the following tests were all reported as normal in each testing session for every subject: modified Amsler grid, red dot test, confrontational visual fields, color vision and fundus photography. Overall, no statistically significant differences were observed for any of the measures, except for both near and far visual acuity, which increased during the course of the study. This difference is not considered clinically relevant as may result from the effect of learning. Intraocular pressure results suggest a small increase at the beginning of the bed rest phase (p=0.059) and lesser increase at post-bed rest with respect to baseline (p=0.046). These preliminary results provide the basis for further analyses that will include correlations between intraocular pressure change pre- and post-bed rest, and optical coherence tomography measurements of the retina.

Cromwell, Ronita L.↗
NASA NTRS2013

Association Between Cardiovascular and Intraocular Pressure Changes in a 14-Day 6 deg Head Down Tilt (HDT) Bed Rest Study: Possible Implications in Retinal Anatomy

Visual symptoms and intracranial pressure increase reported in astronauts returning from long duration missions in low Earth-orbit are thought to be related to fluid shifts within the body due to microgravity exposure. Because of this possible relation to fluid shifts, studies conducted in head-down tilt (HDT) bed rest are being monitored for potential changes in ocular health. These measures will also serve to determine whether HDT is a suitable ground-based analog to model subclinical cardiovascular and ocular changes that could shed light on the etiology of the VIIP syndrome observed in spaceflight. Sixteen healthy normotensive (12M, 4F, age range 29-54 years), non-smoker and normal weight subjects, volunteered to participate in a 14 day 6 deg head HDT study conducted at the NASA Flight Analogs Research Unit (FARU). This facility provides standard bed rest conditions (diet, wake/sleep time, time allowed in sunlight) during the time that the subjects stay at the FARU. Cardiovascular parameters were obtained in supine posture at BR-5, BR+0, and BR+3 and ocular monitoring was performed weekly. Intraocular pressure (IOP) increased from pre-bed rest BR-3) to the third day into bed rest (BR+3). Values reached a plateau towards the end of the bed rest phase (BR10) and decreased within the first three days of recovery (BR+2) returning to levels comparable to baseline at BR-3. As expected, most cardiovascular parameters were affected by 14 days of HDT bed rest. Plasma volume decreased as a result of bed rest but recovered to baseline levels by BR+3. Indications of cardiovascular deconditioning included increase in both systolic and diastolic blood pressure and heart rate, and a decrease in stroke volume and cardiac output between BR-5 and BR+3. Due to the experimental design of this study, we were not able to test the hypothesis that fluid shifts might be involved in the IOP increase during the bed rest phase, since cardiovascular measures were not available for those time points. There was no correlation between the largest change in IOP (BR-3 versus BR3) and cardiovascular measure changes between baseline (BR-5) and post bed rest (BR+2). While no clinically relevant visual changes were observed during the study, measurement of various retinal parameters was performed with optical coherence tomography (OCT). A decrease in central subfield retinal thickness was observed between BR+2 and baseline at BR-10, but no association was observed with IOP changes. This work investigates the time course of changes in IOP during 14-day HDT bed rest in an attempt to characterize HDT bed rest as a model of the VIIP syndrome and delve into its etiology.

Cromwell, Ronita↗
NASA NTRS2014

Effects of Long Duration Spaceflight on Venous and Arterial Compliance

The visual impairment and intracranial pressure syndrome (VIIP) is a newly described space flight-associated medical condition made up of a constellation of symptoms affecting at least 34% of American astronauts who have flown International Space Station (ISS) missions. VIIP is defined primarily by visual acuity deficits and anatomical changes to eye structures, and is thought to be related to elevated intracranial pressure secondary to space flightinduced cephalad fluid shifts. Loss of visual acuity could be a significant threat to crew health and performance and may be suggestive of other adaptations with implications for years post-flight. Our primary objective is to determine whether vascular compliance is altered by space flight and whether such adaptations are related to the incidence of VIIP. In particular, we will measure ocular parameters and vascular compliance in vessels of the head and neck in astronauts who have no space flight experience, in astronauts before, during, and after space flight, and in bed rest subjects with conditions similar to space flight. Additionally, we will analyze astronaut data from the Lifetime Surveillance of Astronaut Health (LSAH) archive to determine which factors might be predictive of the development of VIIP. The project will be conducted in four separate but related parts. To understand the baseline condition of astronauts without any prior space flight experience, we will study 10 astronauts who have never flown in space by performing a comprehensive evaluation of the vasculature of the head, neck and eyes. Hemodynamic data (stroke volume and blood pressure), ocular (tonometry and ocular ultrasound), venous and arterial parameters will be acquired across a range of tilt angles (20, 10, 0, -10, -20 degrees). Vessels to be studied include the temporal, jugular, and vertebral veins and the cerebral, carotid and vertebral arteries. Ophthalmic data from the annual physical will be obtained through data sharing. To examine the relation between vascular compliance in the head and neck and the development of VIIP after a long duration space flight, we will study 10 astronauts before, during, and after long-duration ISS missions. Pre- and post-flight testing will be identical to that described above. During flight, images of the same vessels of interest will be obtained for later analysis. Ophthalmic data including VIIP scores will be obtained through data sharing from medically-required tests. To investigate the effects of age and elevated sodium intake, two potential contributors to VIIP, we will study 24 men (in two age groups: 25-35 and 45-55) during a 14 day 6deg head-down bed rest, a well-accepted analog of space flight. Standard NASA bed rest conditions will be maintained except for dietary sodium. Sodium intake will be similar to that of ISS astronauts, which is higher than consumed in previous bed rest studies. Pre- and post-bed rest testing procedures will be identical to the testing protocol described above for astronauts. Ophthalmic testing (optical coherence tomography, fundoscopy, and tonometry) will be conducted on the same day that vascular compliance measures are obtained. To identify parameters that may relate to an increase in an astronaut's susceptibility to developing VIIP, we will use data mining techniques to evaluate astronaut data obtained from the LSAH. Medical history, family history, space flight history and its related exposures, and history of high performance jet aircraft exposure will be examined for their potential relationship to ocular data. We hypothesize that the cephalad fluid shift induced by space flight will result in structural and functional adaptations in head and neck vessels leading to decreased vascular compliance and related to the development of VIIP symptoms. Further, although VIIP has not been observed in previous bed rest studies, we hypothesize that an elevated sodium intake will increase the incidence of VIIP symptoms in this space flight analog. Finally, we hypothesize that data mining analyses will reveal relationships between health history, previous exposures (including space flight and high performance aircraft), and the development of VIIP in the astronaut population.

Ribeiro, L. C.↗
NASA NTRS2014

Visual Impairment/lntracranial Pressure Risk Clinical Care Data Tools

Prior to 2010, several ISS crewmembers returned from spaceflight with changes to their vision, ranging from a mild hyperopic shift to frank disc edema. As a result, NASA expanded clinical vision testing to include more comprehensive medical imaging, including Optical Coherence Tomography and 3 Tesla Brain and Orbit MRIs. The Space and Clinical Operations (SCO) Division developed a clinical practice guideline that classified individuals based on their symptoms and diagnoses to facilitate clinical care. For the purposes of clinical surveillance, this classification was applied retrospectively to all crewmembers who had sufficient testing for classification. This classification is also a tool that has been leveraged for researchers to identify potential risk factors. In March 2014, driven in part by a more comprehensive understanding of the imaging data and increased imaging capability on orbit, the SCO Division revised their clinical care guidance to outline in‐flight care and increase post‐flight follow up. The new clinical guidance does not include a classification scheme

Van Baalen, Mary↗
NASA NTRS2015

Astronaut Preflight Cardiovascular Variables Associated with Vascular Compliance are Highly Correlated with Post-Flight Eye Outcome Measures in the Visual Impairment Intracranial Pressure (VIIP) Syndrome Following Long Duration Spaceflight

The detection of the first VIIP case occurred in 2005, and adequate eye outcome measures were available for 31 (67.4%) of the 46 long duration US crewmembers who had flown on the ISS since its first crewed mission in 2000. Therefore, this analysis is limited to a subgroup (22 males and 9 females). A "cardiovascular profile" for each astronaut was compiled by examining twelve individual parameters; eleven of these were preflight variables: systolic blood pressure, pulse pressure, body mass index, percentage body fat, LDL, HDL, triglycerides, use of anti‐lipid medication, fasting serum glucose, and maximal oxygen uptake in ml/kg. Each of these variables was averaged across three preflight annual physical exams. Astronaut age prior to the long duration mission, and inflight salt intake was also included in the analysis. The group of cardiovascular variables for each crew member was compared with seven VIIP eye outcome variables collected during the immediate post‐flight period: anterior-posterior axial length of the globe measured by ultrasound and optical biometry; optic nerve sheath diameter, optic nerve diameter, and optic nerve to sheath ratio‐ each measured by ultrasound and magnetic resonance imaging (MRI), intraocular pressure (IOP), change in manifest refraction, mean retinal nerve fiber layer (RNFL) on optical coherence tomography (OCT), and RNFL of the inferior and superior retinal quadrants. Since most of the VIIP eye outcome measures were added sequentially beginning in 2005, as knowledge of the syndrome improved, data were unavailable for 22.0% of the outcome measurements. To address the missing data, we employed multivariate multiple imputation techniques with predictive mean matching methods to accumulate 200 separate imputed datasets for analysis. We were able to impute data for the 22.0% of missing VIIP eye outcomes. We then applied Rubin's rules for collapsing the statistical results across our 200 multiply imputed data sets to assess the canonical correlation between the eye outcomes and the twelve astronaut cardiovascular variables available for all 31 subjects. Results: A highly significant canonical correlation was observed among the canonical solutions (p<.00001), with an average best canonical correlation of.97. The results suggest a strong association between astronauts' measures of cardiovascular health and the seven eye outcomes of the VIIP syndrome used in this analysis. Furthermore, the "joint test" revealed a significant difference in cardiovascular profile between male and female astronauts (Prob > F = 0.00001). Overall, female astronauts demonstrated a significantly healthier cardiovascular status. Individually, the female astronauts had significantly healthier profiles on seven of twelve cardiovascular variables than the men (p values ranging from <0.0001 to <0.05). Male astronauts did not demonstrate significantly healthier values on any of the twelve cardiovascular variables measured

Otto, Christian↗
NASA NTRS2015

Fluid Shifts

INTRODUCTION: Mechanisms responsible for the ocular structural and functional changes that characterize the visual impairment and intracranial pressure (ICP) syndrome (VIIP) are unclear, but hypothesized to be secondary to the cephalad fluid shift experienced in spaceflight. This study will relate the fluid distribution and compartmentalization associated with long-duration spaceflight with VIIP symptoms. We also seek to determine whether the magnitude of fluid shifts during spaceflight, as well as the VIIP-related effects of those shifts, can be predicted preflight with acute hemodynamic manipulations, and also if lower body negative pressure (LBNP) can reverse the VIIP effects. METHODS: Physiologic variables will be examined pre-, in- and post-flight in 10 International Space Station crewmembers including: fluid compartmentalization (D2O and NaBr dilution); interstitial tissue thickness (ultrasound); vascular dimensions and dynamics (ultrasound and MRI (including cerebrospinal fluid pulsatility)); ocular measures (optical coherence tomography, intraocular pressure, ultrasound); and ICP measures (tympanic membrane displacement, otoacoustic emissions). Pre- and post-flight measures will be assessed while upright, supine and during 15 deg head-down tilt (HDT). In-flight measures will occur early and late during 6 or 12 month missions. LBNP will be evaluated as a countermeasure during HDT and during spaceflight. RESULTS: The first two crewmembers are in the preflight testing phase. Preliminary results characterize the acute fluid shifts experienced from upright, to supine and HDT postures (increased stroke volume, jugular dimensions and measures of ICP) which are reversed with 25 millimeters Hg LBNP. DISCUSSION: Initial results indicate that acute cephalad fluid shifts may be related to VIIP symptoms, but also may be reversible by LBNP. The effect of a chronic fluid shift has yet to be evaluated. Learning Objectives: Current spaceflight VIIP research is described, including novel hardware and countermeasures.

Stenger, M. B.↗
NASA NTRS2016

Hindlimb Suspension (HLS) in Rodents for the Study of Intracranial Pressure, Molecular and Histologic Changes in the Eye, and CSF Production Regulation and Resorption: A Status Report of Two Studies

This status report corresponds to two studies tied to an animal experiment being executed at the University of California Davis (Charles Fuller's laboratory). The animal protocol uses the well-documented rat hindlimb suspension (HLS) model, to examine the relationship between cephalic fluid shifts and the regulation of intracranial (ICP) and intraocular (IOP) pressures as well as visual system structure and function. Long Evans rats are subjected to HLS durations of 7, 14, 28 and 90 days. Subgroups of the 90-day animals are studied for recovery periods of 7, 14, 28 or 90 days. All HLS subjects have age-matched cage controls. Various animal cohorts are planned for this study: young males, young females and old males. In addition to the live measures (ICP by telemetry, IOP and retinal parameters by optical coherence tomography) which are shared with the Fuller study, the specific outcomes for this study include: -Gene expression analysis of the retina -Histologic analysis - Analysis of the microvasculature of retina flat mounts by NASA's VESsel GENeration Analysis (VESGEN) Software. To date, the young male and female cohorts are being completed. Due to the need to keep technical variation to a minimum, the histologic and genomic analyses have been delayed until all samples from each cohort are available and can be processed in a single batch per cohort. The samples received so far correspond to young males sacrificed at 7,14, 28 and 90 days of HLS and at 90 days of recovery; and from young females sacrificed at 7, 14 and 28 of HLS. A complementary study titled: "A gene expression and histologic approach to the study of cerebrospinal fluid (CSF) production and outflow in hindlimb suspended rats" seeks to study the molecular components of CSF production and outflow modulation as a result of HLS, bringing a molecular and histologic approach to investigate genome wide expression changes in the arachnoid villi and choroid plexus of HLS rats compared to rats in normal posture.

Theriot, C. A.↗
NASA NTRS2016

Validation of a Cephalad Fluid Shift Countermeasure

INTRODUCTION: This project will provide critical data required to objectively determine how an optimized thigh cuff could be incorporated into the NASA integrated physiological countermeasure suite. This project will determine if thigh cuffs used during simulated spaceflight impact intracranial pressure (ICP), ocular structure and function, and intraocular pressure (IOP) using state of-the-art techniques. Additionally, some of the same methods, hardware, and protocols will be employed in the present investigation to enable direct comparisons to the International Space Station (ISS) "Fluid Shifts" experiment with Chibis-Lower Body Negative Pressure (LBNP). This study will determine the temporal physiological responses of thigh cuff application and removal on ocular and cerebral variables (including invasive ICP) in a microgravity analog. Furthermore, this proposed study will determine tissue pressure distribution applied by thigh cuffs in order to improve comfort, mobility, and efficacy of the countermeasure. Our specific aim is to determine the efficacy of a novel thigh cuff device to mitigate cephalad fluid shifts. We hypothesize that a thigh cuff countermeasure employed in a microgravity analog will temporarily reverse or attenuate ocular and cerebral-volume-pressure variables, approaching normal Earth-based seated posture, the most frequent posture assumed in daily life. In addition, we hypothesize that the magnitude of fluid and pressure redistribution using a thigh cuff countermeasure may require a longer exposure time than that of Chibis-LBNP (using ground-based data from our "Fluid Shifts" project). This project directly addresses Critical Path Roadmap Risks and Questions regarding "Risk of Spaceflight-Induced Intracranial Hypertension/Vision Alterations," and IRP Gap VIIP13: We need to identify preventative and treatment countermeasures to mitigate changes in ocular structure and function and intracranial pressure during spaceflight. METHODS: Noninvasive measures and tissue pressure distributions beneath thigh cuffs The objectives of this study are to: 1) determine the distribution of skin surface pressures beneath the advanced thigh cuff in ten subjects, 2) calibrate the built-in pressure measurement system of the advanced thigh cuff using an industry standard device, and 3) collect subjective feedback and data on the new cuff design to allow for further adjustments prior to invasive studies. A Tekscan Industrial Sensing (I-Scan) system will measure the pressure distribution of the advanced thigh cuff against the skin. In addition, we will measure blood pooling in the thigh and record the circumference of the thigh using Hokanson strain gauge plethysmography. The advanced thigh cuff will be adjusted to obtain a skin contact pressure of 30-50 mmHg as visualized on the Tekscan system. The built-in advanced thigh cuff pressure monitor will be recorded simultaneously to allow direct comparison to the Tekscan measurements. The volunteer will then remove the thigh cuff and remain at rest for five minutes with no legging applied. The thigh cuff will be donned again and pressure measurements will be taken in the same manner for up to 10 repetitions to show reproducibility of pressure after donning. At the conclusion of the study, subjects will be asked to flex their knee, stand, walk, and sit with the thigh cuff activated. During each of these maneuvers the subject will rate their pain/comfort using a modified Borg scale. Effect of thigh cuffs on ICP during simulated microgravity Ommaya reservoir patients will be recruited from the John Wayne Cancer Institute. Ommaya reservoirs provide safe and direct access for the measurement of ICP. Subjects will be instrumented for continuous blood pressure, ECG, and invasive ICP measures. The subjects will be positioned in the upright sitting posture for a 10-minute stabilization period. After the 10-minute stabilization period, imaging measures [ICP, Optical Coherence Tomography, IOP, ocular and vascular ultrasound] will be performed. Following baseline seated measures, the subject will be positioned randomly in the supine, 15deg head-down-tilt, and 15deg head-down-tilt with thigh cuffs and measures repeated. DISCUSSION: Tests to down-select thigh cuff designs will occur in early 2016. Invasive ICP and noninvasive eye imaging tests will begin in spring 2016. Supported by NSBRI through NCC 9-58.

Macias, B.↗
NASA NTRS2016

Proteomic Assessment of Fluid Shifts and Association with Visual Impairment and Intracranial Pressure in Twin Astronauts

BACKGROUND: Astronauts participating in long duration space missions are at an increased risk of physiological disruptions. The development of visual impairment and intracranial pressure (VIIP) syndrome is one of the leading health concerns for crew members on long-duration space missions; microgravity-induced fluid shifts and chronic elevated cabin CO2 may be contributing factors. By studying physiological and molecular changes in one identical twin during his 1-year ISS mission and his ground-based co-twin, this work extends a current NASA-funded investigation to assess space flight induced "Fluid Shifts" in association with the development of VIIP. This twin study uniquely integrates physiological and -omic signatures to further our understanding of the molecular mechanisms underlying space flight-induced VIIP. We are: (i) conducting longitudinal proteomic assessments of plasma to identify fluid regulation-related molecular pathways altered by long-term space flight; and (ii) integrating physiological and proteomic data with genomic data to understand the genomic mechanism by which these proteomic signatures are regulated. PURPOSE: We are exploring proteomic signatures and genomic mechanisms underlying space flight-induced VIIP symptoms with the future goal of developing early biomarkers to detect and monitor the progression of VIIP. This study is first to employ a male monozygous twin pair to systematically determine the impact of fluid distribution in microgravity, integrating a comprehensive set of structural and functional measures with proteomic, metabolomic and genomic data. This project has a broader impact on Earth-based clinical areas, such as traumatic brain injury-induced elevations of intracranial pressure, hydrocephalus, and glaucoma. HYPOTHESIS: We predict that the space-flown twin will experience a space flight-induced alteration in proteins and peptides related to fluid balance, fluid control and brain injury as compared to his pre-flight protein/peptide signatures. Conversely, the trajectory of these protein signatures will remain relatively constant in his ground based co-twin. METHODS: We are using proteomic and standard immunoelectrophoresis techniques to delineate the change in protein signatures throughout the course of a long duration space flight in relation to the development of VIIP. We are also applying a novel cell-based metaboloic organ system assay ("Organs on a Plate") to address how these circulating biomarkers affect physiological processes at the cellular and organ level which could result in VIIP symptoms. These molecular data will be correlated with physiological measures (eg. extra and intracellular fluid volume, vascular filling/flow patterns, MRI, and Optic Coherence Tomography. DISCUSSION: Pre- and in-flight data collection is in progress for the space-flown twin, and similar data have been obtained from the ground-based twin. Biosamples will be batch processed when received from ISS after the conclusion of the 1-year mission. Omic and Physiological measures from the twin astronauts will be compared to similar data being collected on twin subjects who participated in simulated microgravity study. bed rest study.

Rana, Brinda K.↗
NASA NTRS2017

Renin-Angiotensin System (RAS) in Hematopoietic Stem/Progenitor Cells (HS/PC) Predicts Vaso-Reparative Dysfunction and Progression of Diabetic Retinopathy (DR)

Purpose: We tested the hypothesis that loss of angiotensin converting enzyme 2 (ACE2) within diabetic HS/PCs (Hematopoietic Stem/Progenitor Cells) would be detrimental to HS/PC reparative function, and alter their ability to contribute to vascular remodeling in human subjects and rodent models of DR (Diabetic Retinopathy). Methods: Subjects (n52) were recruited as controls (n13) or diabetics (n39) with either no DR, mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR or proliferative DR (PDR). Fluorescein angiograms were analyzed using Vessel Generation Analysis (VESGEN) software in a cohort of subjects. CD34+ HS/PCs were isolated from peripheral blood. RAS (Renin-Angiotensin System) gene expression and migration was measured. Diabetic ACE2 knockout (KO)C57BL6-Ins2 (Akita) mice at 3, 6 and 9 months of diabetes were compared to age-matched controls. Bone marrow HS/PC populations were analyzed by flow cytometry and migration and proliferation studies performed. Results: ACE2 gene expression in human CD34+ cells from diabetics without DR was increased compared to controls (p0.0437). Mas receptor mRNA was also increased in diabetics without DR, but reduced with the onset of NPDR (p0.0002), suggesting a loss of compensation. DR was associated with CD34+ cell migratory dysfunction. By VESGEN analysis, vessel density measured by several confirming parameters in early NPDR (n3) was greater than in normal retina (n6) in both arteries and veins, which suggests active retinal remodeling. ACE2KO-Akita and Akita cohorts showed reduced retinal thickness by OCT (Optical Coherence Tomography) at 9 months of diabetes. Absence of ACE2 in 9-month Akita mice led to an accelerated increase in acellular capillaries compared to diabetic alone. Electroretinogram (ERG) in ACE2KO-Akita mice resulted in persistent deterioration of the neural retina. Reparative function studies showed that ACE2KO exacerbated diabetes-induced impairment of LK (Low Potassium) cell migration and proliferative functions as early as 3-month of diabetes (p0.0019). Conclusions: Retinopathy and adverse vascular remodeling in subjects with diabetes was associated with a loss of the protective arm of RAS in HS/PCs. Loss of ACE2 exacerbated vascular dysfunction in diabetic mice.

retina↗
NASA NTRS2020

Evaluation of Tablet-Based Methods for Assessment of Contrast Sensitivity

Some astronauts have suffered degradation of vision during long-duration space flight, suffering from a condition that has come to be known as Spaceflight Associated Neuro-ocular Syndrome (SANS). While related morphological changes can be observed with imaging technologies such as optical coherence tomography (OCT), it may be useful to have a rapid method for functional vision assessment. In this paper, we compare three tablet-based methods for rapid assessment of contrast sensitivity. First, a relatively novel method developed expressly for touch screens, in which the subject ”swipes” a frequency/contrast sweep grating to indicate the boundary between visible and invisible patterns; second, a method-of-adjustment task in which the subject adjusts the contrast of a grating patch up and down to bracket the visual threshold; and third, a traditional temporal two-alternative forced choice (2AFC) task, in which the subject is presented with a near-threshold stimulus in one of two intervals, and must report the interval containing the stimulus. The swipe method shows variability comparable to the 2AFC method, and shows good agreement in estimates of the spatial frequency of peak sensitivity. The absolute sensitivity estimated with the swipe method is higher than that of the other methods, perhaps because subjects are biased to trace outside of the visible pattern region, or perhaps due to stimulus differences.

Mulligan, Jeffrey B.↗
NASA NTRSDate not supplied

Mitigating Headward Fluid Shifts with Venoconstrictive Thigh Cuffs during Spaceflight

Venoconstrictive thigh cuffs (VTC) are a mechanical countermeasure capable of attenuating the spaceflight induced headward fluid shift, and thus may be a viable spaceflight associated neuro-ocular syndrome (SANS) countermeasure. Crewmembers can use VTC to mitigate the headward fluid shift to aid in adapting to spaceflight. However, data are needed to determine if VTC affect ocular structures. PURPOSE The purpose of this study is to determine the efficacy of long duration use of VTC application to mitigate the spaceflight-induced headward fluid shift. We hypothesize that a VTC countermeasure will temporarily reverse the headward fluid shift and attenuate spaceflight-induced changes of internal jugular vein (IJV) cross-sectional area, IJV pressure, stroke volume, cardiac output, intraocular pressure (IOP), and optic nerve head and retinal morphology. METHODS This study will evaluate the effectiveness of VTC countermeasure application on the headward fluid shift, as well as cardiovascular and ocular variables. VTC during spaceflight will be worn for an extended duration (up to 6 hours) with data collected at three time points (30 minutes, 3 hours, and 6 hours) to characterize the temporal profile of key fluid shift outcome measures of the vascular fluid shift, IOP, and ocular structure changes. Ten astronauts will be recruited to participate and will be studied before and during approximately 180-day International Space Station (ISS) spaceflight missions. Baseline data collection will occur approximately 90-days before launch (Figure). Preflight, each leg of the crewmember will be measured to determine the VTC cuff size and a cuff fit check session will occur prior to the preflight baseline ground imaging to verify the appropriate fit measured via a surface contact pressure. Prior to donning the VTC, baseline measures without VTC will be collected seated, supine, and supine followed by data collection with the VTC. The baseline data collection will include ultrasound (IJV area and pressure, stroke volume and cardiac output), brachial blood pressure and heart rate, optical coherence tomography (OCT) imaging (total retinal thickness and choroid thickness), and IOP. An inflight cuff fit check session, same as the preflight fit check, will occur prior to VTC use on ISS. The inflight VTC experiment will be conducted early (FD45) and late (R-45) to determine if mission duration affects VTC fit and the efficacy of fluid redistribution. A system usability scale comfort questionnaire will be included in each VTC session to capture feedback from crewmembers regarding the comfort and usability of the VTC. SCIENTIFIC & MISSION IMPACT Results will narrow knowledge gaps described in the Human Research Roadmap to mitigate the headward fluid shift during spaceflight and help NASA to 1) determine the efficacy of extended use VTC application to mitigate the spaceflight-induced headward fluid shift and 2) further the understanding of the use of VTC on vascular fluid shifts, IOP, and ocular structure during spaceflight. Supported by NASA Human Research Program Directed Research. Figure. Detailed Testing Schedule. Baseline data collection at L-90 will be performed in a randomized order of position.

J V Jasien↗
NASA NTRSDate not supplied

Correlated Changes in Retinal Thickness and Visuomotor Function in Asymptomatic Plaquenil Toxicity Patients

We have previously shown that a 5-minute eye-movement test can capture a number of largely independent “oculometric” parameters of human visual/visuomotor function (Liston & Stone, 2014). This test has been successfully used to characterize mild neural impairment due to traumatic brain injury, sleep and circadian disruption, and alcohol consumption (Liston et al., 2017; Stone et al, 2019; Tyson et al, 2021). Here, we extend this approach to study patients at risk of progressive posterior-segment illness to see how oculometrics relate to standard clinical ophthalmological measures. Five female patients (<20:40 BCVA, 34-60 years old) undergoing hydroxychloroquine treatment (2-7mg/kg/day for 10-23 years for rheumatologic illness) have participated thus far. Under monocular viewing conditions in randomized order, they tracked a moving spot undergoing radial step-ramp motion in one of 90 randomized directions, at one of 5 randomized speeds, starting at random times (for details, see Stone et al, 2019). We computed nine independent oculometrics (latency, initial acceleration, steady-state gain, proportion smooth, saccadic rate, saccadic amplitude, direction noise, speed responsiveness, and speed noise). Spectral-domain optical coherence tomography (Zeiss, Dublin, CA) was used to measure the average thickness of the nine Early Treatment Diabetic Retinopathy Study macular sectors from the internal limiting membrane to the retinal pigmented epithelium. We used Pearson’s correlation between retinal thickness and our oculometrics with t-statistics to test separate one-sided hypotheses across 10 retinae. Our preliminary analysis found significant changes in several different aspects of visuomotor performance. Most notably, latency increased, initial acceleration decreased, and steady-state pursuit gain decreased as retinal thickness decreased (r2 = 0.364, 0.579, and 0.692; one-tailed P = 0.032, 0.005, and 0.001, respectively). Speed responsiveness appeared to decrease, but this effect was marginal for our current sample (r2 = 0.253, P = 0.069). Lastly, direction discrimination and saccadic behavior appeared unchanged. We conclude that oculometrics may provide sensitive measures of changes in retinal thickness. More importantly, oculometrics have the potential to detect impairment before it becomes evident with standard clinical imaging tools, while also providing insight into the behavioral implications of any resulting deficits in visual/visuomotor function.

eye movements↗
NASA NTRSDate not supplied

An Oculometric Standard to Assess the Performance of the Ocular System for Long Duration Spaceflight

Changes in the human brain, due to spaceflight, have been a challenge to the space program since its inception; a challenge that is becoming more acute as extended International Space Station (ISS) missions become routine, a return to crewed lunar exploration is about to begin, and a multi-year crewed trip to Mars is being planned. Determining the extent to which neurophysiological adaptations may adversely impact performance in operational tasks, assessing the full-time course of these changes, and identifying/mitigating any potential long-term health consequences are crucial steps required to enable safe crew-autonomous, long-duration, deep-space missions. Vision is the predominant perceptual sense used to guide cognition and motor control in humans. Thus, it is critical for the success of any future, long-duration mission to understand how long-term exposure to microgravity and to other stressors of spaceflight and their interactions, impact visual function. This is an especially challenging task given the small and disparate samples from which we have been and will be able to collect human performance data. NASA has recently been carefully tracking spaceflight-induced ophthalmic changes, driven in large part by the fluid shifts related to microgravity. In particular, a recent study of Optical Coherence Tomography (OCT) postflight measures revealed that more than two-thirds of US crew members experience significant increases in retinal thickness after 6month or longer ISS missions. Space Associated Neuro-ocular Syndrome (SANS) also includes visual acuity decrements and other ocular structural changes that could adversely impact in-flight performance as missions become longer. However, the impact of spaceflight on the visual system is not limited to the retina. Recent comparisons of pre-and post-flight brain images have revealed structural changes throughout the brain that implicate visual, visuomotor, and visual-cognitive pathways, consistent with observed functional impacts (e.g., decreased speed/accuracy/timing of fine goal-oriented movements). Current limitations on inflight testing make it very difficult to determine when and under what conditions SANS and other disruptions of human neurological subsystems arise. Currently, one cannot anticipate the time course and extent of impairment and recovery. This study addresses this knowledge gap by creating an integrated framework of the relevant existing literature on visual and oculomotor function during spaceflight with an eye towards complementing current structural measures of visuomotor impairment with new oculometric standard measures. Using eye-movement based visual function assessment and diagnostics would provide a valuable enhancement of crew health and performance monitoring in support of deepspace exploration.

Vision↗
NASA NTRSDate not supplied

SPACEFLIGHT ASSOCIATED NEURO-OCULAR SYNDROME (SANS): 2023 CLINICAL UPDATE

INTRODUCTION Spaceflight Associated Neuro-ocular Syndrome (SANS) is a condition unique to long-duration spaceflight, with an unclear pathogenesis and pathophysiology, and no perfect terrestrial analog. Approximately 66% of long duration spaceflight (LDSF) astronauts present with the earliest indication of SANS, which is defined as development of any of the following signs in at least one eye during or immediately following spaceflight: 1) optic disc edema (ODE; represented by an increase of ≥ 20 microns in peripapillary total retinal thickness [ΔTRT]); 2) chorioretinal folds; 3) globe flattening; and 4) excessive shift in refractive error (≥ +0.75D). Each of these signs presents potential risk to a crewmember’s vision and mission effectiveness, with ODE posing the highest risk overall. It is not yet known what severity and/or duration of these signs might lead to acute or permanent impacts to ocular anatomy or visual performance. Brain anatomical changes also occur during long-duration spaceflight and are being monitored in the astronaut population; however, these changes have not yet been associated with functional decrements or with SANS. An update will be provided on the latest SANS clinical analyses, diagnostics, and program initiatives. METHODS Data were obtained from clinical records and SANS subject matter experts (SMEs) to compile a SANS clinical update. Areas of interest include: 1) prevalence of SANS signs, 2) defining clinical thresholds for SANS, and 3) an overview of current and planned SANS clinical efforts. DISCUSSION SANS Sign Prevalence: Analysis at the time of this abstract submission indicates that the approximate prevalence of primary SANS findings in USOS LDSF crewmembers is: 64% for ODE (≥ 20-micron ΔTRT), 15% for chorioretinal folds, 26% for globe flattening, and 14% for hyperopic shifts in refractive error (≥ +0.75D). Clinical Thresholds:  The Earliest Indication of SANS was presented publicly for the first time at the 2020 NASA Human Research Program Investigators’ Workshop. See definition in Introduction section (above).  Clinically Concerning SANS – Development of any of the following signs during or immediately following spaceflight: 1) ODE (≥ 55-micron ΔTRT* and/or Frisèn grade ≥1*), 2) sharp chorioretinal folds in the vicinity of the macula, or 3) moderate globe flattening.  Pathological SANS with an Acute Functional Impact – Development of any of the following signs/symptoms during or immediately following spaceflight: 1) visual field loss (e.g., enlarged blindspot), 2) distorted centralvision, or 3) shift in refractive error beyond power of available correction (e.g., “space anticipation glasses”).  Pathological SANS affecting Long-Term Health – Development of any of the following signs/symptoms during or following spaceflight: 1) permanent visual field loss, 2) reduced retinal nerve fiber layer (RNFL) thickness, 3) permanently distorted central vision, 4) atrophy of retinal pigment epithelium (RPE) or photoreceptors, or 5) choroidal neovascularization. Current & Planned Clinical Efforts (accurate at time of abstract submission): All SANS diagnostic hardware are performing nominally onboard the International Space Station: vision screening, fundoscope, optical coherence tomography (OCT) device, ultrasound, and tonometer. The Goggle-Based Visual Field (GBVF) device is nearing completion of its clinical validation study at Ohio State University and is planned for parabolic flight testing in fiscal year 2023 (FY23); pending positive results, this sequence may pave the way towards an ISS technology demonstration in FY24.

T J Brunstetter↗