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Reference earth orbital research and applications investigations (blue book). Volume 8: Life sciences

The functional program element for the life sciences facilities to operate aboard manned space stations is presented. The life sciences investigations will consist of the following subjects: (1) medical research, (2) vertebrate research, (3) plant research, (4) cells and tissue research, (5) invertebrate research, (6) life support and protection, and (7) man-system integration. The equipment required to provide the desired functional capability for the research facilities is defined. The goals and objectives of each research facility are described.

Source record↗

Characterization of Evidence for Human System Risk Assessment

Understanding the kinds of evidence available and using the best evidence to answer a question is critical to evidenced-based decision-making, and it requires synthesis of evidence from a variety of sources. Categorization of human system risks in spaceflight, in particular, focuses on how well the integration and interpretation of all available evidence informs the risk statement that describes the relationship between spaceflight hazards and an outcome of interest. A mature understanding and categorization of these risks requires: 1) sufficient characterization of risk, 2) sufficient knowledge to determine an acceptable level of risk (i.e., a standard), 3) development of mitigations to meet the acceptable level of risk, and 4) identification of factors affecting generalizability of the evidence to different design reference missions. In the medical research community, evidence is often ranked by increasing confidence in findings gleaned from observational and experimental research (e.g., "levels of evidence"). However, an approach based solely on aspects of experimental design is problematic in assessing human system risks for spaceflight. For spaceflight, the unique challenges and opportunities include: (1) The independent variables in most evidence are the hazards of spaceflight, such as space radiation or low gravity, which cannot be entirely duplicated in terrestrial (Earth-based) analogs, (2) Evidence is drawn from multiple sources including medical and mission operations, Lifetime Surveillance of Astronaut Health (LSAH), spaceflight research (LSDA), and relevant environmental & terrestrial databases, (3) Risk metrics based primarily on LSAH data are typically derived from available prevalence or incidence data, which may limit rigorous interpretation, (4) The timeframe for obtaining adequate spaceflight sample size (n) is very long, given the small population, (5) Randomized controlled trials are unattainable in spaceflight, (6) Collection of personal and environmental data on the astronaut population may create opportunities for advanced analytics and human-environment modeling that goes beyond that achieved in isolated experimental designs; and (7) Translation of relevant research to operations is a complex, transdisciplinary enterprise in which the approach must apply across the physical, biological, behavioral, and social sciences. The approach to synthesizing evidence must address both source and fidelity of data, and reflect the most general attributes of quality of evidence in science and engineering: reliability and validity. The authors are developing a two-factor approach which includes the various kinds of evidence required to understand risks and for the integrated interpretation of all evidence that is essential to develop standards and countermeasures. A unified framework for aggregating and assessing different kinds of evidence provides a consistent, traceable, evidence-based decision-making process to translate research to operations in an environment where engineers, scientists, physicians, and managers all engage in analyzing the trade space of vehicle design, standards, requirements and solutions for spaceflight.

Steinberg, S. L.↗

Reliability Models and Attributable Risk

The intention of this report is to bring a developing and extremely useful statistical methodology to greater attention within the Safety, Reliability, and Quality Assurance Office of the NASA Johnson Space Center. The statistical methods in this exposition are found under the heading of attributable risk. Recently the Safety, Reliability, and Quality Assurance Office at the Johnson Space Center has supported efforts to introduce methods of medical research statistics dealing with the survivability of people to bear on the problems of aerospace that deal with the reliability of component hardware used in the NASA space program. This report, which describes several study designs for which attributable risk is used, is in concert with the latter goals. The report identifies areas of active research in attributable risk while briefly describing much of what has been developed in the theory of attributable risk. The report, which largely is a report on a report, attempts to recast the medical setting and language commonly found in descriptions of attributable risk into the setting and language of the space program and its component hardware.

Jarvinen, Richard D.↗

Use of shuttle for life sciences

The use of the space shuttle in carrying out biological and medical research programs, with emphasis on the sortie module, is examined. Detailed descriptions are given of the goals of space life science disciplines, how the sortie can meet these goals, and what shuttle design features are necessary for a viable biological and medical experiment program. Conclusions show that the space shuttle sortie module is capable of accommodating all biological experiments contemplated at this time except for those involving large specimens or large populations of small animals; however, these experiments can be done with a specially designed module. It was also found that at least two weeks is required to do a meaningful survey of biological effects.

Mcgaughy, R. E.↗

Keeping a Beat on the Heart

Feel the relief of a patient suffering from heart arrhythmia, who is able to return home while having her heart monitored by health professionals 24 hours a day, without the fear that she will miss an important indicator and suffer a fatal heart attack - using technology originally developed to conduct experiments on the Space Shuttle. Approximately 400,000 Americans die every year from sudden heart attacks . Medical research revealed that patterns of electrical activity in the heart can act as predictors of these lethal cardiac events known as arrhythmias. Fortunately, certain arrhythmias such as ventricular fibrillation (loss of regular heartbeat and subsequent loss of function) and ventricular tachycardia (rapid heartbeats), can be detected and appropriately treated. Today, patients at moderate risk of arrhythmias can benefit from technology that would permit long- term continuous monitoring of electrical cardiac rhythms outside the hospital environment in the comfort of their own homes. Medical telemetry systems, also known as telemedicine, are evolving rapidly as wireless communication technology advances, evidenced by the commercial products and research prototypes for remote health monitoring that have appeared in recent years. Wireless systems allow patients to move freely in their home and work environment while being monitored remotely by health care professionals.

Liszka, Kathy J.↗

Cyclotron resonance accelerators for industrial applications

Here, this paper describes novel configurations for cyclotron resonance acceleration of electrons and ions that have several attractive features including: a compact robust room-temperature single-cell RF cavity as the accelerator structure; and continuous high current accelerated un-bunched beam output with self-scanning, obviating need for a separate beam scanner. An electron accelerator version, the electron Cyclotron Resonance Accelerator (eCRA), is under development to be an efficient source for high power electron and x-ray beams for medical, research, sterilization, and National Security applications, so as to replace radioactive materials. An ion accelerator version, the ion Cyclotron Auto-Resonance Accelerator (iCARA) is described here, suggesting its potential to produce, as an example, a high-current multi-MeV beam of deuterons which could be highly competitive with that produced either with linacs or cyclotrons. Such a deuteron beam could produce a high flux of fast neutrons via deuteron stripping, for applications including the transmutation of used nuclear fuel, material studies relevant for a fusion reactor inner wall, tritium breeding and medical isotope production. For the high-current, high efficiency simulated performance for eCRA and iCARA as described in this paper, the particle beams produced may not exhibit the low emittance values that are important for most discovery research. Rather, the beams could be useful for industrial applications where higher emittance and some energy spread can be tolerated, in favor of high beam power.

43 PARTICLE ACCELERATORS↗

NASA Omics Archive Project

The space environment consists of a complex set of hazards including altered gravity, radiation, psychological/physiological stress, isolation, and confinement leading to complex biological responses. Advances in biotechnology capabilities offer considerable potential to provide novel insight into those responses as well as innovative diagnostic, treatment, and countermeasure solutions for astronauts as NASA begins to travel beyond low Earth orbit. Omics data (genomics, transcriptomics, proteomics, etc.) is one example that can provide NASA with critical knowledge of how a crewmember’s genetics, environment, and lifestyle can be used to develop individualized approaches for disease prevention, advance diagnostics, and improve treatment strategies. NASA ventured into the field of omics on human subjects with the successful completion of the NASA Twins Study which was the first step in mapping the multi-omic profile of astronauts to understand and mitigate the health consequences of spaceflight. The Human Research Program aims to build upon the success of the Twins Study with the NASA Omics Archive flight study, establishing a longitudinal biospecimen archive and efficiently generating a comprehensive high-quality multi-omic dataset from astronauts for the purpose of studying molecular, metabolic, and microbial changes associated with longduration spaceflight missions. The goal is to facilitate scientific and medical research community efforts to characterize and mitigate spaceflight health and performance risks. In this presentation, we will review details regarding the biospecimen and data archive to be generated by the NASA Omics Archive flight study. Data generated as part of this project will be archived in the NASA Life Sciences Portal (NLSP) and be made available for future hypothesis-driven research efforts or occupational surveillance through Institutional Review Board-approved data sharing and retrospective data requests submitted to the Life Sciences Data Archive (LSDA) team. We will also present results of a ground study performed to evaluate in-house procedures, new sample collection hardware, and vendor capabilities. The data repository generated and the samples to be archived by this study will enable future research efforts to assess an astronauts’ unique molecular and genetic profile with respect to individual spaceflight responses. Results of which will be instrumental in enabling precision health capabilities to better assess and mitigate spaceflight risks, detect disease states earlier, and actively monitor countermeasure treatments, ultimately improving clinical outcomes during future exploration class missions.

C. A. Theriot↗

Space research - At a crossroads

Efforts which must be expended if U.S. space research is to regain vitality in the next few years are discussed. Small-scale programs are the cornerstone for big science projects, giving both researchers and students a chance to practice the development of space missions and hardware and identify promising goals for larger projects. Small projects can be carried aloft by balloons, sounding rockets, the Shuttle and ELVs. It is recommended that NASA continue the development of remote sensing systems, and join with other government agencies to fund space-based materials science, space biology and medical research. Increased international cooperation in space projects is necessary for affording moderate to large scale missions, for political reasons, and to maximize available space resources. Finally, the establishment and funding of long-range goals in space, particularly the development of the infrastructure and technologies for the exploration and colonization of the planets, must be viewed as the normal outgrowth of the capabilities being developed for LEO operations.

Mcdonald, Frank B.↗

Photon Activation Analysis in Gallium, Nickel, and Vanadium

Here this research explored the development of the photonuclear production method of 67 Cu from 71 Ga as well as 47 Sc from 51 V. Both products serve as high-demand research medical radioisotopes. Furthermore, an understanding of these reactions is significant to fundamental nuclear physics and astrophysics. Bremsstrahlung flux was induced by an electron linac and a 1-mm tungsten radiator. Irradiation of gallium oxide powder, 98.78% pure 71 Ga, and a natural vanadium foil at 30.9 MeV and 100 W for 1 h produced 64.4 ± 0.4 Bq/W·s·kg of 67 Cu and 164 ± 3.1 Bq/W·s·kg of 47 Sc. A secondary irradiation with 99.6% pure 71 Ga and natural vanadium at 31.5 MeV and 100 W for 1.1 h produced 79.8 ± 0.9 Bq/W·s·kg of 67 Cu and 136 ± 7.2 Bq/W·s·kg of 47 Sc. The photoinduced activation is promising; however, further research into optimal geometry and power is required to maximize specific activity. Natural nickel was also irradiated to serve as a benchmark comparison. Effective cross sections for each reaction were inferred.

47Sc↗

Risk Assessment and Control through Countermeasure System Iplementation for Long-term Crew Exposure to Microgravity

Experience with the International Space Station (ISS) program demonstrates the degree to which engineering design and operational solutions must protect crewmembers from health risks due to long-term exposure to the microgravity environment. Risks to safety and health due to degradation in the microgravity environment include crew inability to complete emergency or nominal activities, increased risk of injury, and inability to complete safe return to the ground due to reduced strength or embrittled bones. These risks without controls slowly increase in probability for the length of the mission and become more significant for increasing mission durations. Countermeasures to microgravity include hardware systems that place a crewmember s body under elevated stress to produce an effect similar to daily exposure to gravity. The ISS countermeasure system is predominately composed of customized exercise machines. Historical treatment of microgravity countermeasure systems as medical research experiments unintentionally reduced the foreseen importance and therefore the capability of the systems to function in a long-term operational role. Long-term hazardous effects and steadily increasing operational risks due to non-functional countermeasure equipment require a more rigorous design approach and incorporation of redundancy into seemingly non- mission-critical hardware systems. Variations in the rate of health degradation and responsiveness to countermeasures among the crew population drastically increase the challenge for design requirements development and verification of the appropriate risk control strategy. The long-term nature of the hazards and severe limits on logistical re-supply mass, volume and frequency complicates assessment of hardware availability and verification of an adequate maintenance and sparing plan. Design achievement of medically defined performance requirements by microgravity countermeasure systems and incorporation of adequate failure tolerance significantly reduces these risks. Future implementation of on-site monitoring hardware for critical health parameters such as bone mineral density would allow greater responsiveness, efficiency, and optimized design of the countermeasures system.

Gernand, Jeremy M.↗

Technology Applications Team: Applications of aerospace technology

Highlights of the Research Triangle Institute (RTI) Applications Team activities over the past quarter are presented in Section 1.0. The Team's progress in fulfilling the requirements of the contract is summarized in Section 2.0. In addition to our market-driven approach to applications project development, RTI has placed increased effort on activities to commercialize technologies developed at NASA Centers. These Technology Commercialization efforts are summarized in Section 3.0. New problem statements prepared by the Team in the reporting period are presented in Section 4.0. The Team's transfer activities for ongoing projects with the NASA Centers are presented in Section 5.0. Section 6.0 summarizes the status of four add-on tasks. Travel for the reporting period is described in Section 7.0. The RTI Team staff and consultants and their project responsibilities are listed in Appendix A. The authors gratefully acknowledge the contributions of many individuals to the RTI Technology Applications Team program. The time and effort contributed by managers, engineers, and scientists throughout NASA were essential to program success. Most important to the program has been a productive working relationship with the NASA Field Center Technology Utilization (TU) Offices. The RTI Team continues to strive for improved effectiveness as a resource to these offices. Industry managers, technical staff, medical researchers, and clinicians have been cooperative and open in their participation. The RTI Team looks forward to continuing expansion of its interaction with U.S. industry to facilitate the transfer of aerospace technology to the private sector.

Source record↗

Distribution Development for Residual Inventory at the New York West Valley Site - 20400

The New York State Energy Research and Development Authority (NYSERDA) is the owner of the Western New York Nuclear Service Center (WNYNSC), a 1,351 ha site located approximately 48 km south of Buffalo, New York. In 1962, Nuclear Fuel Services, Inc. (NFS) entered into Agreements with the Atomic Energy Commission and New York State to construct the first commercial reprocessing plant of nuclear fuel in the United States. NFS, a private company, built and operated the spent fuel reprocessing plant and waste disposal facilities, processing 640 Mg of spent nuclear fuel from 1966 to 1972 under an Atomic Energy Commission license. Nuclear fuel reprocessing operations ended in 1972 and never reopened, leaving behind radioactive and chemical wastes. Operations led to contamination in a number of facilities and locations. Some of that contamination has migrated from waste disposal zones to other layers, formations, and features on and off the WNYNSC. Phase I decommissioning activities are ongoing and involve the removal of a number of areas and structures that have been associated with contamination. The purpose of this work is to outline the approach for characterizing contamination not associated with disposed wastes, contaminated structures, or specific releases. In this work, the term, residual radiological activity, is used to describe environmental contamination that exists subsequent to the completion of Phase I decommissioning activities, that is not associated with disposed wastes, contaminated structures, or specific releases. Contamination from the Site was quantified relative to data that characterize the concentrations of radionuclides that exist in background. Background concentrations are those present in the area but having no influence from Site related activities. The existence of residual radiological activity that is elevated relative to background has the potential to contribute to future risks to human health and the environment. As a consequence, the residual inventory information is used to inform the West Valley Probabilistic Performance Assessment (PPA) model to characterize potential future risks to human health and the environment. The centralized West Valley Data Management System (DMS) was the source of information for the data assembled in this analysis. The DMS is a fairly large compilation consisting of thousands of records from investigation studies, with sample dates ranging from 1990 to present. Samples from monitoring wells, boreholes, geoprobe studies, surface water, surface soils, storm water outfalls, ventilation stack filters, plant and animal tissues, and more are included in the DMS. Results are typically reported in units of activity per unit volume. For the purpose of the analyses presented here, all results were converted into consistent units of pCi per unit volume. Since 1990, data have been collected from various locations across the WNYNSC at different times with varying frequency over the course of several decades. As a consequence, a number of potential issues can arise with respect to the assembly of a dataset that is deemed adequate for the characterization of residual radiological activity. These issues were assessed and resolved to the extent possible through careful consideration of the properties of the distributions. The intent was to use data which characterize the current state of the Site. Radionuclides can be designated to one of several groups depending on their origin. In this work the groups considered were 1) Naturally Occurring Radioactive Material (NORM), 2) fallout, and 3) Other (including power plant, medical research, etc). This grouping is a useful construct with respect to the interpretation of fixed laboratory results. For example, NORM radionuclides that exist within a decay chain should have approximately equivalent distributions of concentrations if they are representative of background conditions. Insights such as these can be used as a check to identify sample results that need to be further investigated or omitted due to issues associated with reported results from fixed laboratory analyses. This type of analysis provided a foundation for the assessment of the adequacy of sample results for use in subsequent components of an assessment. The general process for the assessment of residual radiological contamination at the Site consists of a sequence of several steps. First, for each analyte, several statistical tests were performed to assess the weight of evidence against the null hypothesis that the mean of the distribution of concentrations was equal to zero. If the mean of the distribution of concentrations for a given radionuclide was not found to be greater than zero, then it was removed from consideration as a component of the residual radiological contamination. If there was significant evidence to reject the hypothesis of the mean being equal to zero, the second step was to compare the distribution of the data from the Site to that of the corresponding background. A suite of tests was used to compare the distributions of the site and background data. The results of these tests were collectively used to determine if site data are elevated relative to background. The third step was to develop distributions using a Bayesian framework to characterize the distribution of mean of the increment present above background for each of the radionuclides. The Bayesian model implemented allowed for the comparison of site-specific records to background concentrations to better approximate contamination attributed to the Site. A final screening step was employed for radionuclides that exceed background. This screening step compared 95% upper confidence limits (UCLs) from the increment distribution developed in the previous step to the risk screening levels. This approach yields a list of analytes that were determined to be elevated relative to background.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Continuous assessment of metabolic activity of mitochondria using resonance Raman microspectroscopy

Dysfunctional mitochondrial activity can lead to a variety of different diseases. As such, there exists a need to quantify changes in mitochondria function as it relates to these specific diseased states. Here, we present the use of resonance Raman (RR) spectroscopy as a tool to determine changes in isolated mitochondrial activity. RR spectroscopy, using 532 nm as the excitation source, specifically provides information on the reduction and oxidation (RedOx) state of cytochrome c, which is determined by the activity of protein complexes in the electron transport chain. In this model, injection of the substrate succinate into the mitochondrial sample is used to drive the electron transport chain, which causes a subsequent change in cytochrome c RedOx state. This change in RedOx state is tracked by RR spectroscopy. We report this tool gives real-time information on the rise and fall of the amount of reduced cytochrome c within the mitochondrial sample, providing a method for rapid assessment of mitochondrial metabolism that has broad applications in both basic science and medical research.

59 BASIC BIOLOGICAL SCIENCES↗

Microstructure and microchemistry changes at U-10Mo fuel/AA6061 cladding interfaces with varying hot isostatic pressing conditions

Monolithic uranium - 10 wt.% molybdenum (U-10Mo) is a promising high-assay low-enriched uranium fuel system for nuclear reactors used in research, medical isotope production, and remote power applications. During manufacturing, AA6061 cladding is bonded to the U-10Mo fuel plate via hot isostatic pressing, during which diffusion and fuel/cladding chemical interaction occurs at plate edges. Furthermore, the microstructure and microchemistry changes that occur at fuel/cladding interfaces are important to understand as a function of process parameters to develop a reliable fuel fabrication process and to meet the desired specifications. Here, microstructural and microchemical changes are studied using complementary electron microscopy and atom probe tomography for two manufactured fuel plates with varied hot isostatic pressing (HIP) parameters. Results highlight that modifying thermomechanical processing parameters significantly changed the interaction layer thickness between U-10Mo and AA6061 by an order of magnitude. In addition to this the distribution and concentration of elements (i.e., Al, Si, Mg) from cladding to fuel was also investigated.

36 MATERIALS SCIENCE↗

Coupling a recurrent neural network to SPAD TCSPC systems for real-time fluorescence lifetime imaging

Fluorescence lifetime imaging (FLI) has been receiving increased attention in recent years as a powerful diagnostic technique in biological and medical research. However, existing FLI systems often suffer from a tradeoff between processing speed, accuracy, and robustness. Inspired by the concept of Edge Artificial Intelligence (Edge AI), we propose a robust approach that enables fast FLI with no degradation of accuracy. This approach couples a recurrent neural network (RNN), which is trained to estimate the fluorescence lifetime directly from raw timestamps without building histograms, to SPAD TCSPC systems, thereby drastically reducing transfer data volumes and hardware resource utilization, and enabling real-time FLI acquisition. We train two variants of the RNN on a synthetic dataset and compare the results to those obtained using center-of-mass method (CMM) and least squares fitting (LS fitting). Results demonstrate that two RNN variants, gated recurrent unit (GRU) and long short-term memory (LSTM), are comparable to CMM and LS fitting in terms of accuracy, while outperforming them in the presence of background noise by a large margin. To explore the ultimate limits of the approach, we derive the Cramer-Rao lower bound of the measurement, showing that RNN yields lifetime estimations with near-optimal precision. To demonstrate real-time operation, we build a FLI microscope based on an existing SPAD TCSPC system comprising a 32 x 32 SPAD sensor named Piccolo. Four quantized GRU cores, capable of processing up to 4 million photons per second, are deployed on the Xilinx Kintex-7 FPGA that controls the Piccolo. Powered by the GRU, the FLI setup can retrieve real-time fluorescence lifetime images at up to 10 frames per second. The proposed FLI system is promising and ideally suited for biomedical applications, including biological imaging, biomedical diagnostics, and fluorescence-assisted surgery, etc.

47 OTHER INSTRUMENTATION↗

Cross sections of 147–149 Sm( 6 Li,x) reactions for the production of 149 Tb for targeted alpha therapy

Terbium-149g (t 1/2 = 4.12 h) is of particular interest for targeted alpha therapy cancer treatment due to its ability to decay via both alpha and positron emission, making it a potential theranostic nuclide. Due to many challenges facing its production, there are limited facilities worldwide that have demonstrated the ability to produce this nuclide in quantities sufficient for medical research. Since the Cyclotron Institute at Texas A&M University is a specialized accelerator facility capable of accelerating a wide variety of ions, we are investigating production pathway options. One of the major challenges facing its production is the known co-production of the excited isomeric state, 149m Tb (t 1/2 = 4.1 min). However, this state does not decay to the ground state of 149g Tb, negating any potential contribution to its yield. Due to its short-half life, the cross section for the population of this state has never been measured. After calculating several potential reaction yields using predictive models, the reactions of 147–149 Sm( 6 Li,xn) 149 Tb were identified as candidates. Lithium-6 beams of varied energies between 45-65 MeV were impinged on enriched 147 Sm, 148 Sm, and 149 Sm targets at the Cyclotron Institute at Texas A&M University, and the reaction products were measured immediately following irradiation using high-purity germanium detectors, enabling detection of both 149m Tb and 149g Tb. Cross sections for all nuclides produced in sufficient activity in these reactions were also measured and reported here. We conclude that the population of 149m Tb is much preferred over population of the ground state for these 6 Li-induced reactions, and it is necessary to explore other options for 149g Tb production.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Comparison of Different Variants of the U.S. Army Occupational Physical Assessment Test

The U.S. Army Occupational Physical Assessment Test (OPAT) is a pre-enlistment physical employment screening assessment developed to place recruits and soldiers into Military Occupational Specialties (MOSs) based on their physical capabilities in order to optimize performance and limit injury. The OPAT consists of the seated power throw (SPT), strength deadlift (SDL), standing long jump, and interval aerobic run. During the scientific validation of the OPAT, two variants of the SPT and two variants of the SDL were used. Although the OPAT was validated using both variants for each test, U.S. Army scientists and policymakers have received queries regarding how these variants compare to each other. Therefore, the purpose of this study was to compare different variants of the SPT and SDL. Thirty-two participants (14 male and 18 female) between the ages of 18 and 42 years visited the laboratory on one occasion and performed two variants of the SPT (seated on the ground [the current OPAT standard] versus seated in a chair with a 35 cm seat height) and two variants of the SDL (using a hex-bar [the current OPAT standard] versus using paired dumbbells). Testing order for the different variants was randomized. The protocol was approved by the U.S. Army Medical Research and Development Command Institutional Review Board. Performing the SPT from a chair significantly (P < .05) increased performance when compared to performing the SPT from the ground (5.4 ± 1.3 m versus 5.0 ± 1.4 m, respectively). Values for the two SPT variants were correlated (tau = 0.90). Performing the SDL using the hex-bar significantly increased the maximal weight lifted when compared to performing the SDL using paired dumbbells (86.9 ± 18.4 kg versus 83.1 ± 18.0 kg, respectively). Values for the two SDL variants were correlated (tau = 0.83). Performing different variants of the SPT and SDL influenced the resulting score. Although these findings do not alter the administration or scoring of the OPAT, they do provide a valuable reference in the event of future inquiries regarding the development of the OPAT.

General & Internal Medicine↗

Comparative Performance of Three Eye-Tracking Devices in Detection of Mild Traumatic Brain Injury in Acute Versus Chronic Subject Populations

ABSTRACT Introduction Presently, traumatic brain injury (TBI) triage in field settings relies on symptom-based screening tools such as the updated Military Acute Concussion Evaluation. Objective eye-tracking may provide an alternative means of neurotrauma screening due to sensitivity to neurotrauma brain-health changes. Previously, the US Army Medical Research and Development Command Non-Invasive NeuroAssessment Devices (NINAD) Integrated Product Team identified 3 commercially available eye-tracking devices (SyncThink EYE-SYNC, Oculogica EyeBOX, NeuroKinetics IPAS) as meeting criteria toward being operationally effective in the detection of TBI in service members. We compared these devices to assess their relative performance in the classification of mild traumatic brain injury (mTBI) subjects versus normal healthy controls. Materials and Methods Participants 18 to 45 years of age were assigned to Acute mTBI, Chronic mTBI, or Control group per study criteria. Each completed a TBI assessment protocol with all 3 devices counterbalanced across participants. Acute mTBI participants were tested within 72 hours following injury whereas time since last injury for the Chronic mTBI group ranged from months to years. Discriminant analysis was undertaken to determine device classification performance in separating TBI subjects from controls. Area Under the Curves (AUCs) were calculated and used to compare the accuracy of device performance. Device-related factors including data quality, the need to repeat tests, and technical issues experienced were aggregated for reporting. Results A total of 63 participants were recruited as Acute mTBI subjects, 34 as Chronic mTBI subjects, and 119 participants without history of TBI as controls. To maximize outcomes, poorer quality data were excluded from analysis using specific criteria where possible. Final analysis utilized 49 (43 male/6 female, mean [x̅] age = 24.3 years, SD [s] = 5.1) Acute mTBI subjects, and 34 (33 male/1 female, x̅ age = 38.8 years, s = 3.9) Chronic mTBI subjects were age- and gender-matched as closely as possible with Control subjects. AUCs obtained with 80% of total dataset ranged from 0.690 to 0.950 for the Acute Group and from 0.753 to 0.811 for the Chronic mTBI group. Validation with the remaining 20% of dataset produced AUCs ranging from 0.600 to 0.750 for Acute mTBI group and 0.490 to 0.571 for the Chronic mTBI group. Conclusions Potential eye-tracking detection of mTBI, per training model outcomes, ranged from acceptable to excellent for the Acute mTBI group; however, it was less consistent for the Chronic mTBI group. The self-imposed targeted performance (AUC of 0.850) appears achievable, but further device improvements and research are necessary. Discriminant analysis models differed for the Acute versus Chronic mTBI groups, suggesting performance differences in eye-tracking. Although eye-tracking demonstrated sensitivity in the Chronic group, a more rigorous and/or longitudinal study design is required to evaluate this observation. mTBI injuries were not controlled for this study, potentially reducing eye-tracking assessment sensitivity. Overall, these findings indicate that while eye-tracking remains a viable means of mTBI screening, device-specific variability in data quality, length of testing, and ease of use must be addressed to achieve NINAD objectives and DoD implementation.

General & Internal Medicine↗