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NASA NTRS2017

Spaceflight Effect on White Matter Structural Integrity

Recent reports of elevated brain white matter hyperintensity (WMH) counts and volume in postflight astronaut MRIs suggest that further examination of spaceflight's impact on the microstructure of brain white matter is warranted. To this end, retrospective longitudinal diffusion-weighted MRI scans obtained from 15 astronauts were evaluated. In light of the recent reports of microgravity-induced cephalad fluid shift and gray matter atrophy seen in astronauts, we applied a technique to estimate diffusion tensor imaging (DTI) metrics corrected for free water contamination. This approach enabled the analysis of white matter tissue-specific alterations that are unrelated to fluid shifts, occurring from before spaceflight to after landing. After spaceflight, decreased fractional anisotropy (FA) values were detected in an area encompassing the superior and inferior longitudinal fasciculi and the inferior fronto-occipital fasciculus. Increased radial diffusivity (RD) and decreased axial diffusivity (AD) were also detected within overlapping regions. In addition, FA values in the corticospinal tract decreased and RD measures in the precentral gyrus white matter increased from before to after flight. The results show disrupted structural connectivity of white matter in tracts involved in visuospatial processing, vestibular function, and movement control as a result of spaceflight. The findings may help us understand the structural underpinnings of the extensive spaceflight-induced sensorimotor remodeling. Prospective longitudinal assessment of the white matter integrity in astronauts is needed to characterize the evolution of white matter microstructural changes associated with spaceflight, their behavioral consequences, and the time course of recovery. Supported by a grant from the National Space Biomedical Research Institute, NASA NCC 9-58.

Lee, Jessica K.↗

NASA NTRS2001

Mapping visual cortex in monkeys and humans using surface-based atlases

We have used surface-based atlases of the cerebral cortex to analyze the functional organization of visual cortex in humans and macaque monkeys. The macaque atlas contains multiple partitioning schemes for visual cortex, including a probabilistic atlas of visual areas derived from a recent architectonic study, plus summary schemes that reflect a combination of physiological and anatomical evidence. The human atlas includes a probabilistic map of eight topographically organized visual areas recently mapped using functional MRI. To facilitate comparisons between species, we used surface-based warping to bring functional and geographic landmarks on the macaque map into register with corresponding landmarks on the human map. The results suggest that extrastriate visual cortex outside the known topographically organized areas is dramatically expanded in human compared to macaque cortex, particularly in the parietal lobe.

Non-NASA Center↗

NASA NTRS1991

Automated rendezvous and docking with video imagery

For rendezvous and docking, assessing and tracking relative orientation is necessary within a minimum approach distance. Special target light patterns have previously been considered for use with video sensors for ease of determining relative orientation. A generalization of those approaches is addressed. At certain ranges, the entire structure of the target vehicle constitutes an acceptable target; at closer ranges, substructures will suffice. Acting on the same principle as the human intelligence, these structures can be compared with a memory model to assess the relative orientation and range. Models for comparison are constructed from a CAD facet model and current imagery. This approach requires fast image handling, projection, and comparison techniques which rely on rapidly developing parallel processing technology. Relative orientation and range assessment consists of successful comparison of the perceived target aspect with a known aspect. Generating a known projection from a model within required times, say subsecond times, is only now approaching feasibility. With this capability, rates of comparison used by the human brain can be approached and arbitrary known structures can be compared in reasonable times. Future space programs will have access to powerful computation devices which far exceed even this capability. For example, the possibility will exist to assess unknown structures and then control rendezvous and docking, all at very fast rates. The first step which has the current utility, namely applying this to known structures, is taken.

Rodgers, Mike↗

NASA NTRS2017

Intracranial Fluid Redistribution During a Spaceflight Analog

The neural correlates of spaceflight-induced sensorimotor impairments are unknown. Head down-tilt bed rest (HDBR) serves as a microgravity analog because it mimics the headward fluid shift and limb unloading of spaceflight. We investigated focal brain white matter (WM) changes and fluid shifts during 70 days of 6 deg HDBR in 16 subjects who were assessed pre (2x), during (3x), and post-HDBR (2x). Changes over time were compared to those in control subjects (n=12) assessed four times over 90 days. Diffusion MRI was used to assess WM microstructure and fluid shifts. Free-Water Imaging, derived from diffusion MRI, was used to quantify the distribution of intracranial extracellular free water (FW). Additionally, we tested whether WM and FW changes correlated with changes in functional mobility and balance measures. HDBR resulted in FW increases in fronto-temporal regions and decreases in posterior-parietal regions that largely recovered by two weeks post-HDBR. WM microstructure was unaffected by HDBR. FW decreased in the post-central gyrus and precuneus. We previously reported that gray matter increases in these regions were associated with less HDBR-induced balance impairment, suggesting adaptive structural neuroplasticity. Future studies are warranted to determine causality and underlying mechanisms.

Koppelmans, Vincent↗

NASA NTRS1993

A petabyte size electronic library using the N-Gram memory engine

A model library containing petabytes of data is proposed by Triada, Ltd., Ann Arbor, Michigan. The library uses the newly patented N-Gram Memory Engine (Neurex), for storage, compression, and retrieval. Neurex splits data into two parts: a hierarchical network of associative memories that store 'information' from data and a permutation operator that preserves sequence. Neurex is expected to offer four advantages in mass storage systems. Neurex representations are dense, fully reversible, hence less expensive to store. Neurex becomes exponentially more stable with increasing data flow; thus its contents and the inverting algorithm may be mass produced for low cost distribution. Only a small permutation operator would be recalled from the library to recover data. Neurex may be enhanced to recall patterns using a partial pattern. Neurex nodes are measures of their pattern. Researchers might use nodes in statistical models to avoid costly sorting and counting procedures. Neurex subsumes a theory of learning and memory that the author believes extends information theory. Its first axiom is a symmetry principle: learning creates memory and memory evidences learning. The theory treats an information store that evolves from a null state to stationarity. A Neurex extracts information data without a priori knowledge; i.e., unlike neural networks, neither feedback nor training is required. The model consists of an energetically conservative field of uniformly distributed events with variable spatial and temporal scale, and an observer walking randomly through this field. A bank of band limited transducers (an 'eye'), each transducer in a bank being tuned to a sub-band, outputs signals upon registering events. Output signals are 'observed' by another transducer bank (a mid-brain), except the band limit of the second bank is narrower than the band limit of the first bank. The banks are arrayed as n 'levels' or 'time domains, td.' The banks are the hierarchical network (a cortex) and transducers are (associative) memories. A model Neurex was built and studied. Data were 50 MB to 10 GB samples of text, data base, and images: black/white, grey scale, and high resolution in several spectral bands. Memories at td, S(m(sub td)), were plotted against outputs of memories at td-1. S(m(sub td)) was Boltzman distributed, and memory frequencies exhibited self-organized criticality (SOC); i.e., 'l/f(sup beta)' after long exposures to data. Whereas output signals from level n may be encoded with B(sub output) = O(-log(2)f(sup beta)) bits, and input data encoded with B(sub input) = O((S(td)/S(td-1))(sup n)), B(sup output)/B(sub input) is much less than 1 always, the Neurex determines a canonical code for data and it is a lossless data compressor. Further tests are underway to confirm these results with more data types and larger samples.

Bugajski, Joseph M.↗

NASA NTRS1995

Safety analysis

We are engaged in a research program in safety-critical computing that is based on two case studies. We use these case studies to provide application-specific details of the various research issues, and as targets for evaluation of research ideas. The first case study is the Magnetic Stereotaxis System (MSS), an investigational device for performing human neurosurgery being developed in a joint effort between the Department of Physics at the University of Virginia and the Department of Neurosurgery at the University of Iowa. The system operates by manipulating a small permanent magnet (known as a 'seed') within the brain using an externally applied magnetic field. By varying the magnitude and gradient of the external magnetic field, the seed can be moved along a non-linear path and positioned at a site requiring therapy, e.g., a tumor. The magnetic field required for movement through brain tissue is extremely high, and is generated by a set of six superconducting magnets located in a housing surrounding the patient's head. The system uses two X-ray cameras positioned at right angles to detect in real time the locations of the seed and of X-ray opaque markers affixed to the patient's skull. the X-ray images are used to locate the objects of interest in a canonical frame of reference. the second case study is the University of Virginia Research Nuclear Reactor (UVAR). It is a 2 MW thermal, concrete-walled pool reactor. The system operates using 20 to 25 plate-type fuel assemblies placed on a rectangular grid plate. There are three scramable safety rods, and one non-scramable regulating rod that can be put in automatic mode. It was originally constructed in 1959 as a 1 MW system, and it was upgraded to 2 MW in 1973. Though only a research reactor rather than a power reactor, the issues raised are significant and can be related to the problems faced by full-scale reactor systems.

Knight, John C.↗

NASA NTRS1999

Dynamical Signatures of Living Systems

One of the main challenges in modeling living systems is to distinguish a random walk of physical origin (for instance, Brownian motions) from those of biological origin and that will constitute the starting point of the proposed approach. As conjectured, the biological random walk must be nonlinear. Indeed, any stochastic Markov process can be described by linear Fokker-Planck equation (or its discretized version), only that type of process has been observed in the inanimate world. However, all such processes always converge to a stable (ergodic or periodic) state, i.e., to the states of a lower complexity and high entropy. At the same time, the evolution of living systems directed toward a higher level of complexity if complexity is associated with a number of structural variations. The simplest way to mimic such a tendency is to incorporate a nonlinearity into the random walk; then the probability evolution will attain the features of diffusion equation: the formation and dissipation of shock waves initiated by small shallow wave disturbances. As a result, the evolution never "dies:" it produces new different configurations which are accompanied by an increase or decrease of entropy (the decrease takes place during formation of shock waves, the increase-during their dissipation). In other words, the evolution can be directed "against the second law of thermodynamics" by forming patterns outside of equilibrium in the probability space. Due to that, a specie is not locked up in a certain pattern of behavior: it still can perform a variety of motions, and only the statistics of these motions is constrained by this pattern. It should be emphasized that such a "twist" is based upon the concept of reflection, i.e., the existence of the self-image (adopted from psychology). The model consists of a generator of stochastic processes which represents the motor dynamics in the form of nonlinear random walks, and a simulator of the nonlinear version of the diffusion equation which represents the mental dynamics. It has been demonstrated that coupled mental-motor dynamics can simulate emerging self-organization, prey-predator games, collaboration and competition, "collective brain," etc.

Zak, M.↗

NASA NTRS2014

Focal Gray Matter Plasticity as a Function of Long Duration Head Down Tilted Bed Rest: Preliminary Results

Long duration spaceflight (i.e., 22 days or longer) has been associated with changes in sensorimotor systems, resulting in difficulties that astronauts experience with posture control, locomotion, and manual control. The microgravity environment is an important causal factor for spaceflight induced sensorimotor changes. Whether these sensorimotor changes are solely related to peripheral changes from reduced vestibular stimulation, body unloading, body fluid shifts or that they may be related to structural and functional brain changes is yet unknown. However, a recent study reported associations between microgravity and flattening of the posterior eye globe and protrusion of the optic nerve [1] possibly as the result of increased intracranial pressure due to microgravity induced bodily fluid shifts [3]. Moreover, elevated intracranial pressure has been related to white matter microstructural damage [2]. Thus, it is possible that spaceflight may affect brain structure and thereby cognitive functioning. Long duration head down tilt bed rest has been suggested as an exclusionary analog to study microgravity effects on the sensorimotor system [4]. Bed rest mimics microgravity in body unloading and bodily fluid shifts. In consideration of the health and performance of crewmembers both in- and post-flight, we are conducting a prospective longitudinal 70-day bed rest study as an analog to investigate the effects of microgravity on brain structure [5]. Here we present results of the first six subjects. Six subjects were assessed at 12 and 7 days before-, at 7, 30, and ~70 days in-, and at 8 and 12 days post 70 days of bed rest at the NASA bed rest facility in UTMB, Galveston, TX, USA. At each time point structural MRI scans (i.e., high resolution T1-weighted imaging and Diffusion Tensor Imaging (DTI)) were obtained using a 3T Siemens scanner. Focal changes over time in gray matter density were assessed using the voxel based morphometry 8 (VBM8) toolbox under SPM. Longitudinal processing in VBM8 includes linear registration of each scan to the mean of the subject and subsequently transforming all scans in to MNI space by applying the warp from the mean subject to MNI to the individual gray matter segmentations. Modulation was applied so that all images represented the volume of the original structure in native space. Voxel wise analysis was carried out on the gray matter images after smoothing, using a flexible factorial design with family wise error correction. Focal changes in white matter microstructural integrity were assessed using tract based spatial statistics (TBSS) as part of FMRIB software library (FSL). TBSS registers all DTI scans to standard space. It subsequently creates a study specific white matter skeleton of the major white matter tracts. For each subject, for each DTI metric (i.e. fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD)), the maximum value in a line perpendicular to the skeleton tract is projected to the skeleton. Non-parametric permutation based t-tests and ANOVA's were used for voxel-wise comparison of the skeletons. For both VBM and TBSS, comparison of pre bed rest measurements did not show significant differences. VBM analysis revealed decreased gray matter density in bilateral areas including the frontal medial cortex, the insular cortex and the caudate (see Figure) from 'pre to in bed rest'. Over the same time period, there was an increase in gray matter density in the cerebellum, occipital-, and parietal cortex, including the precuneus (see Figure). The majority of these changes did not recover from 'during to post bed rest'. TBSS analysis did not reveal significant changes in white matter microstructural integrity after correction for multiple comparisons. Uncorrected analyses (p<.015) revealed an increase in RD in the cerebellum and brainstem from pre bed rest to the first week in bed rest that did not recover post bed rest. Extended bed rest, which is an analog for microgravity, can result in gray matter changes and potentially in microstructural white matter changes in areas that are important for neuro motor behavior and cognition. These changes did not recover at two weeks post bed rest. Whether the effects of bed rest wear off at longer times post bed rest, and if they are associated with behavior are important questions that warrant further research.

Koppelmans, V.↗

NASA NTRS2016

Functional Responses in Otolith Structures from Micro- to Hyper-Gravity

Vertebrates and invertebrates sense gravito-inertial acceleration by mechanoreceptors in the otolith and statolith organs, respectively. These structures consist of ciliated sensory hair cells surmounted by biomineral grains of calcium carbonate (CaCO3) called oto-orstato-conia. The grains provide mechanical loading of hair cell cilia, and their high density increases sensitivity to acceleration. A widely considered mechanism by which the animal responds to a chronic change in amplitude of gravity is a change in weight lending otoconia. In G, it is argued, the organism counters the loss of gravity by increasing CaCO3 production, thereby increasing otolith mass, as a means to increase system gain. In hypergravity (HG), the converse is argued. Here, we present the results obtained in 3 species exposed both to G and HG. Adult toadfish, Opsanus tau, were exposed to G in 2 short-duration shuttle missions and to 1.24 1.73G centrifugation for 1-32 days; re-adaptation was studied following 1-8 days of 1G. Results show a biphasic pattern in response to 1.73G: initial hypersensitivity, similar to that observed after G exposure, followed by transition to a significant decrease at 16-32 days. Recovery from HG exposure is 4-8 days. Next, we examined directly the responses of statocyst receptors in the land snail after exposure to G on two unmanned Russian Orbital missions and at 1.24G. Similar to vertebrate afferents snail receptors increased their sensitivity to tilt after G exposure, and decrease it after 16-32 days of HG. Two major pieces of information are still needed: vertebrate hair cell response to altered gravity and impact of longer duration exposures on sensory plasticity. To address the latter, we applied electron microscopic techniques to image otoconia mass obtained from 1) mice subjected to 91-days of weightlessness in the Mouse Drawer System (MDS) flown on International Space Station, 2) mice subjected to 91-days of 1.24G centrifugation on ground, and 3) mice flown on 2 short-duration orbital missions. Images indicate a clear restructuring of individual otoconia, suggesting deposition to the outer shell. Images from their HG counterparts indicate the converse - an ablation of the otoconia mass. For shorter duration exposures to weightlessness on 13-day shuttle missions, mice otoconia appear normal. Despite the permanence of 1G in evolution, the animal senses exposure to a novel, non-1G, environment and adaptive mechanisms are initiated - in the short term, compensation is likely confined to the peripheral sensory receptors, the brain or both. For longer exposures structural modifications of the endorgan may also result. Support Contributed By: NASA 03-OBPR-04 and 11-11_Omni_2-0002

Vertebrates↗

NASA NTRS1994

Neural network wavelet technology: A frontier of automation

Neural networks are an outgrowth of interdisciplinary studies concerning the brain. These studies are guiding the field of Artificial Intelligence towards the, so-called, 6th Generation Computer. Enormous amounts of resources have been poured into R/D. Wavelet Transforms (WT) have replaced Fourier Transforms (FT) in Wideband Transient (WT) cases since the discovery of WT in 1985. The list of successful applications includes the following: earthquake prediction; radar identification; speech recognition; stock market forecasting; FBI finger print image compression; and telecommunication ISDN-data compression.

Szu, Harold↗

NASA NTRS2011

Multipoint Observations of Coronal Mass Ejection and Solar Energetic Particle Events on Mars and Earth During November 2001

Multipoint spacecraft observations provide unique opportunities to constrain the propagation and evolution of interplanetary coronal mass ejections (ICMEs) throughout the heliosphere. Using Mars Global Surveyor (MGS) data to study both ICME and solar energetic particle (SEP) events at Mars and OMNI and Geostationary Operational Environmental Satellite (GOES) data to study ICMEs and SEPs at Earth, we present a detailed study of three CMEs and flares in late November 2001. In this period, Mars trailed Earth by 56deg solar longitude so that the two planets occupied interplanetary magnetic field lines separated by only approx.25deg. We model the interplanetary propagation of CME events using the ENLIL version 2.6 3-D MHD code coupled with the Wang-Sheeley-Arge version 1.6 potential source surface model, using Solar and Heliospheric Observatory (SOHO) Large Angle and Spectrometric Coronagraph (LASCO) images to determine CME input parameters. We find that multipoint observations are essential to constrain the simulations of ICME propagation, as two very different ICMEs may look very similar in only one observational location. The direction and width of the CME as parameters essential to a correct estimation of arrival time and amplitude of the ICME signal. We find that these are problematic to extract from the analysis of SOHO/LASCO images commonly used for input to ICME propagation models. We further confirm that MGS magnetometer and electron reflectometer data can be used to study not only ICME events but also SEP events at Mars, with good results providing a consistent picture of the events when combined with near-Earth data.

Falkenberg, T. V.↗

NASA NTRS2014

Focal Gray Matter Plasticity as a Function of Long Duration Bedrest: Preliminary Results

Long duration spaceflight (i.e., 22 days or longer) has been associated with changes in sensorimotor systems, resulting in difficulties that astronauts experience with posture control, locomotion, and manual control. It is unknown whether and how spaceflight impacts sensorimotor brain structure and function, and whether such changes may potentially underlie behavioral effects. Long duration head down tilt bed rest has been used repeatedly as an exclusionary analog to study microgravity effects on the sensorimotor system [1]. Bed rest mimics microgravity in body unloading and bodily fluid shifts. We are currently testing sensorimotor function, brain structure, and brain function pre and post a 70‐day bed rest period. We will acquire the same measures on NASA crewmembers starting in 2014. Here we present the results of the first eight bed rest subjects. Subjects were assessed at 12 and 7 days before‐, at 7, 30, and ~70 days in‐, and at 8 and 12 days post 70 days of bed rest at the NASA bed rest facility, UTMB, Galveston, TX, USA. At each time point structural MRI scans (i.e., high resolution T1‐weighted imaging and Diffusion Tensor Imaging (DTI)) were obtained using a 3T Siemens scanner. Focal changes over time in gray matter density were assessed using the voxel based morphometry 8 (VBM8) toolbox under SPM. Focal changes in white matter microstructural integrity were assessed using tract based spatial statistics (TBSS) as part of the FMRIB software library (FSL). TBSS registers all DTI scans to standard space. It subsequently creates a study specific white matter skeleton of the major white matter tracts. Non‐parametric permutation based t‐tests and ANOVA's were used for voxel‐wise comparison of the skeletons. For both VBM and TBSS, comparison of the two pre bed rest measurements did not show significant differences. VBM analysis revealed decreased gray matter density in bilateral areas including the frontal medial cortex, the insular cortex and the caudate nucleus from pre to in bed rest. Over the same time period, there was an increase in gray matter density in the cerebellum, occipital, and parietal cortices. The majority of these changes did not recover from during to post bed rest. TBSS analyses will also be presented. Extended bed rest, which is an analog for microgravity, can result in gray matter changes and potentially in microstructural white matter changes in areas that are important for neuromotor behavior and cognition. These changes did not recover at two weeks post bed rest. These results have significant public health implications, and will also aid in interpretation of our future data obtained pre and post spaceflight. Whether the effects of bed rest wear off at longer times post bed rest, and if they are associated with behavior are important questions that warrant further research.

Koppelmans, V.↗

NASA NTRS2002

Space radiation absorbed dose distribution in a human phantom

The radiation risk to astronauts has always been based on measurements using passive thermoluminescent dosimeters (TLDs). The skin dose is converted to dose equivalent using an average radiation quality factor based on model calculations. The radiological risk estimates, however, are based on organ and tissue doses. This paper describes results from the first space flight (STS-91, 51.65 degrees inclination and approximately 380 km altitude) of a fully instrumented Alderson Rando phantom torso (with head) to relate the skin dose to organ doses. Spatial distributions of absorbed dose in 34 1-inch-thick sections measured using TLDs are described. There is about a 30% change in dose as one moves from the front to the back of the phantom body. Small active dosimeters were developed specifically to provide time-resolved measurements of absorbed dose rates and quality factors at five organ locations (brain, thyroid, heart/lung, stomach and colon) inside the phantom. Using these dosimeters, it was possible to separate the trapped-proton and the galactic cosmic radiation components of the doses. A tissue-equivalent proportional counter (TEPC) and a charged-particle directional spectrometer (CPDS) were flown next to the phantom torso to provide data on the incident internal radiation environment. Accurate models of the shielding distributions at the site of the TEPC, the CPDS and a scalable Computerized Anatomical Male (CAM) model of the phantom torso were developed. These measurements provided a comprehensive data set to map the dose distribution inside a human phantom, and to assess the accuracy and validity of radiation transport models throughout the human body. The results show that for the conditions in the International Space Station (ISS) orbit during periods near the solar minimum, the ratio of the blood-forming organ dose rate to the skin absorbed dose rate is about 80%, and the ratio of the dose equivalents is almost one. The results show that the GCR model dose-rate predictions are 20% lower than the observations. Assuming that the trapped-belt models lead to a correct orbit-averaged energy spectrum, the measurements of dose rates inside the phantom cannot be fully understood. Passive measurements using 6Li- and 7Li-based detectors on the astronauts and inside the brain and thyroid of the phantom show the presence of a significant contribution due to thermal neutrons, an area requiring additional study.

STS-91 Shuttle Project↗

NASA NTRS2019

Oculometric Assessment of Mild Neural Impairment

For over 100 years, neurologists have used eye movements to identify neural impairment, disease, or injury. Prior to the age of modern imaging, qualitative assessment of eye movements was a critical, routine component of diagnosis and remains today a routine law-enforcement tool for detecting impaired driving due to drugs or alcohol. We will describe the application of a simple 5-minute oculomotor tracking task coupled with a broad range of quantitative analyses of high-resolution oculomotor measurements for the sensitive detection of sub-clinical neural impairment and for the potential differentiation of various causes. Specifically, we will show that there are distinct patterns of impairment across our set of oculometric parameters observed with brain trauma, sleep and circadian disruption, and alcohol consumption. Such differences could form the basis of a self-administered medical monitoring or diagnostic support tool.

Stone, Lee↗

NASA NTRS2017

Developmental Research in Space: Predicting Adult Neurobehavioral Phenotypes via Metabolomic Imaging

As human habitation and eventual colonization of space becomes an inevitable reality, there is a necessity to understand how organisms develop over the life span in the space environment. Microgravity, altered CO2, radiation and psychological stress are some of the key factors that could affect mammalian reproduction and development in space, however there is a paucity of information on this topic. Here we combine early (neonatal) in vivo spectroscopic imaging with an adult emotionality assay following a common obstetric complication (prenatal asphyxia) likely to occur during gestation in space. The neural metabolome is sensitive to alteration by degenerative changes and developmental disorders, thus we hypothesized that that early neonatal neurometabolite profiles can predict adult response to novelty. Late gestation fetal rats were exposed to moderate asphyxia by occluding the blood supply feeding one of the rats pair uterine horns for 15min. Blood supply to the opposite horn was not occluded (within-litter cesarean control). Further comparisons were made with vaginal (natural) birth controls. In one-week old neonates, we measured neurometabolites in three brain areas (i.e., striatum, prefrontal cortex, and hippocampus). Adult perinatally-asphyxiated offspring exhibited greater anxiety-like behavioral phenotypes (as measured the composite neurobehavioral assay involving open field activity, responses to novel object, quantification of fecal droppings, and resident-intruder tests of social behavior). Further, early neurometabolite profiles predicted adult responses. Non-invasive MRS screening of mammalian offspring is likely to advance ground-based space analogue studies informing mammalian reproduction in space, and achieving high-priority multigenerational research that will enable studies of the first truly space-developed mammals.

Schorn, Julia M.↗

NASA NTRS2017

Developmental Research in Space: Predicting Adult Neurobehavioral Phenotypes via Metabolomic Imaging

rodent development spacefligh↗

NASA NTRS2014

Maiden Voyage of the Rodent Habitat on ISS: Opportunities for Investigating Molecular Mechanisms and Biomedical Consequences of Long Duration Spaceflight

Research using rodents is an essential tool for advancing biomedical research on Earth and in space. The National Research Counsel’s Decadal survey (1) emphasized the importance of expanding NASAs life sciences research to perform long duration, rodent experiments on the International Space Station (ISS). To accomplish this objective, flight hardware, operations, and science capabilities were developed at NASA ARC to support both commercial and government-sponsored research. In preparation for the maiden voyage of the Rodent Habitat hardware and operations system (Rodent Research-1), and in close consultation with a Science Working Group comprised of veterinarians and experienced spaceflight investigators, we modified existing Animal Enclosure Module hardware, developed new hardware, operations, and science activities, and performed a series of ground-based verification tests. Preflight, ground based hardware tests included a simulation of SpaceX Dragon launch conditions (vibration and hypergravity) using the Transporter, and also two long-term biocompatibility tests (32 and 92 days) using the Habitat developed for long term housing on the ISS. The launch simulation test showed that adult mice housed in Transporter hardware adapted well, even if launch simulation was followed by a period of simulated weightlessness (via hind limb unloading). The biocompatibility tests demonstrated that the Habitat successfully supported animal health and also provided a useful video imaging system that enables frequent monitoring of animal health and behavior by veterinary and scientific experts on the ground, independent of ISS crew intervention. At the conclusion of all tests, mice were deemed healthy and suitable for conducting biological research. Additional preflight analyses of tissues preserved by freezing or fixation for gene expression analyses revealed that spleen and liver tissues recovered under conditions that simulated on-orbit activities yielded high quality RNA (RIN values 8-10) and liver enzyme activities and protein content (e.g. catalase). In addition, new methods were developed to optimize future science return by dissecting tissues post-euthanasia and storage. Various tissues were harvested from either intact or partially dissected, frozen carcasses after storage for ~2-6 months; most of the tissues (brain, heart, kidney, eye, adrenal glands and skeletal muscle) were of high RNA quality for science return, whereas some tissues (small intestine, bone marrow and bones) were not. These data demonstrated the protocols developed for future flight experiments supported science return despite delayed preservation post-euthanasia or prolonged storage, and furthermore, that high-quality RNA samples from many different tissues can be recovered by dissection following prolonged storage of the tissue in situ at -80˚C. The first flight experiments carrying 20 mice were launched on Sept 21, 2014 in an unmanned Dragon Capsule, SpaceX4; Rodent Research-1 is dedicated to achieving both NASA validation and CASIS science objectives. Ground based control groups (housed in flight hardware or standard cages) were maintained in environmental chambers at Kennedy Space Center. Crewmembers previously trained in animal handling transferred mice from the Transporter into Habitats under simultaneous veterinary supervision by video streaming and were deemed healthy. Health and behavior of all mice on the ISS was monitored by video feed on a daily basis. The 10 mice for validation (16wk old, female C57Bl6/J) ambulated freely and actively throughout the Habitat, relying heavily on their forelimbs for locomotion. The first on-orbit dissections of mice were performed successfully on Oct 12 and 13, 2014, and the validation mice will reside on ISS for up to 30 days. In conclusion, new capability for long duration rodent research is under development, including in-flight sample collection (which avoids the complication of reentry); results obtained to date will be described. This new Rodent Research system enables achievement of both basic science and translational research objectives to advance human exploration of space.

maiden voyage↗

NASA NTRS2000

Monitoring Astronaut Health at the Nanoscale Cellular Level Through the Eye

A user friendly goggles-like head-mounted device equipped with a suite of instruments for several non-invasive and quantitative medical evaluation of the eye, skin, and brain is desired for monitoring the health of astronauts during space travel and exploration of neighboring and distant planets. Real-time non-invasive evaluation of the different structures within the above organs can provide indices of the health of not just these organs, but the entire body. The techniques such as dynamic light scattering (for the early detection of uveitis, cholesterol levels, cataract, changes in the vitreous and possibly Alzheimer's disease), corneal autofluorescence (to assess extracellular matrix biology e.g., in diabetes), optical activity measurements (of anterior ocular fluid to evaluate blood-glucose levels), laser Doppler velocimetry (to assess retinal, optic nerve, and choroidal blood flow), reflectometry/oximetry (for assessing ocular and central nervous system oxygen metabolism), optical coherence tomography (to determine retinal tissue microstructure) and possibly scanning laser technology (for intraocular tissue imaging and scanning) will he integrated into this compact device. Skin sensors will also be mounted on the portion of the device in contact with the periocular region. This will enable monitoring of body temperature, EEG, and electrolyte status. This device will monitor astronaut health during long-duration space travel by detecting aberrations from pre-established "nonns", enabling prompt diagnosis and possibly the initiation of early preventative/curative therapy. The non-invasive nature of the device technologies permits frequent repetition of tests, enabling real-time complete crew health monitoring. This device may ultimately be useful in tele-medicine to bring modern healthcare to under-served areas on Earth as well as in so-called "advanced" care settings (e.g. diabetes in the USA).

Ansari, Rafat R.↗