Galactic cosmic ray simulation at the NASA space radiation laboratory - Progress, challenges and recommendations on mixed-field effects.

For missions beyond low Earth orbit to the moon or Mars, space explorers will encounter a complex radiation field composed of various ion species with a broad range of energies. Such missions pose significant radiation protection challenges that need to be solved in order to minimize exposures and associated health risks. An innovative galactic cosmic ray simulator (GCRsim) was recently developed at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL). The GCRsim technology is intended to represent major components of the space radiation environment in a ground analog laboratory setting where it can be used to improve understanding of biological risks and serve as a testbed for countermeasure development and validation. The current GCRsim consists of 33 energetic ion beams that collectively simulate the primary and secondary GCR field encountered by humans in space over the broad range of particle types, energies, and linear energy transfer (LET) of interest to health effects. A virtual workshop was held in December 2020 to assess the status of the NASA baseline GCRsim. Workshop attendees examined various aspects of simulator design, with a particular emphasis on beam selection strategies. Experimental results, modeling approaches, areas of consensus, and questions of concern were also discussed in detail. This report includes a summary of the GCRsim workshop and a description of the current status of the GCRsim. This information is important for future advancements and applications in space radiobiology.

Cardiovascular Disease Risk Modeling for Astronauts: Making the Leap From Earth to Space.

NASA has recently completed several long-duration missions to the International Space Station and is solidifying plans to return to the Moon, with an eye toward Mars and beyond. As NASA pushes the boundaries of human space exploration, the hazards of spaceflight, including space radiation, levy an increasing burden on astronaut health and performance. The cardiovascular system may be especially vulnerable due to the combined impacts of space radiation exposure, lack of gravity, and other spaceflight hazards. On Earth, the risk for cardiovascular disease (CVD) following moderate to high radiation doses is well-established from clinical, environmental, and occupational exposures (largely from gamma- and x-rays). Less is known about CVD risks associated with high-energy charged ions found in space and increasingly used in radiotherapy applications on Earth, making this a critical area of investigation for occupational radiation protection. Assessing CVD risk is complicated by its multifactorial nature, where an individual's risk is strongly influenced by factors such as family history, blood pressure, and lipid profiles. These known risk factors provide the basis for development of a variety of clinical risk prediction models (CPMs) that inform the likelihood of medical outcomes over a defined period. These tools improve clinical decision-making, personalize care, and support primary prevention of CVD. They may also be useful for individualizing risk estimates for CVD following radiation exposure both in the clinic and in space. In this review, we summarize unique aspects of radiation risk assessment for astronauts, and we evaluate the most widely used CVD CPMs for their use in NASA radiation risk assessment applications. We describe a comprehensive dual-use risk assessment framework that supports both clinical care and operational management of space radiation health risks using quantitative metrics. This approach is a first step in using personalized medicine for radiation risk assessment to support safe and productive spaceflight and long-term quality of life for NASA astronauts.

Medical Countermeasure Requirements to Meet NASA's Space Radiation Permissible Exposure Limits for a Mars Mission Scenario.

ABSTRACT: The space radiation environment consists of a complex mixture of ionizing particles that pose significant health risks to crew members. NASA currently requires that an astronaut's career Risk of Exposure Induced Death (REID) for cancer mortality should not exceed 3% at the upper 95% confidence level. This career radiation limit is likely to be exceeded for even the shortest round-trip mission scenario to Mars. As such, NASA has begun to pursue more vigorously approaches to directly reduce radiation risks, despite the large uncertainties associated with such projections. A recent study considered cohort studies of aspirin and warfarin as possible medical countermeasures (MCMs) acting to reduce background cancer mortality rates used in astronaut risk projections. It was shown that such MCMs can reduce the REID for specific tissues in restricted time intervals over which the drugs were administered; however, the cumulative effect on total lifetime REID was minimal. As an extension, the present work addresses more general MCM requirements that would be needed to meet current NASA radiation limits for a Mars mission scenario. A sensitivity analysis is performed within the major components of the NASA cancer risk model that would likely be modified by MCM interventions. This includes the background cancer incidence and mortality rates, epidemiologically based hazard rates derived from acute terrestrial exposures, and radiation quality factors used to translate terrestrial exposures to space radiation. Relationships between possible MCMs and each of these components are discussed. Results from this study provide important information regarding MCM requirements needed to meet NASA limits for planned Mars missions. Insight into the types of countermeasures expected to yield greatest reductions in crew risk is also gained.

Improving astronaut cancer risk assessment from space radiation with an ensemble model framework.

A new approach to NASA space radiation risk modeling has successfully extended the current NASA probabilistic cancer risk model to an ensemble framework able to consider sub-model parameter uncertainty as well as model-form uncertainty associated with differing theoretical or empirical formalisms. Ensemble methodologies are already widely used in weather prediction, modeling of infectious disease outbreaks, and certain terrestrial radiation protection applications to better understand how uncertainty may influence risk decision-making. Applying ensemble methodologies to space radiation risk projections offers the potential to efficiently incorporate emerging research results, allow for the incorporation of future models, improve uncertainty quantification, and reduce the impact of subjective bias. Moreover, risk forecasting across an ensemble of multiple predictive models can provide stakeholders additional information on risk acceptance if current health/medical standards cannot be met for future space exploration missions, such as human missions to Mars. In this work, ensemble risk projections implementing multiple sub-models of radiation quality, dose and dose-rate effectiveness factors, excess risk, and latency are presented. Initial consensus methods for ensemble model weights and correlations to account for individual model bias are discussed. In these analyses, the ensemble forecast compares well to results from NASA's current operational cancer risk projection model used to assess permissible mission durations for astronauts. However, a large range of projected risk values are obtained at the upper 95th confidence level where models must extrapolate beyond available biological data sets. Closer agreement is seen at the median ± one sigma due to the inherent similarities in available models. Identification of potential new models, epidemiological data, and methods for statistical correlation between predictive ensemble members are discussed. Alternate ways of communicating risk and acceptable uncertainty with respect to NASA's current permissible exposure limits are explored.

Earth-Based Research Analogs to Investigate Space-Based Health Risks.

During spaceflight, astronauts are exposed to a variety of unique hazards, including altered gravity fields, long periods of isolation and confinement, living in a closed environment at increasing distances from Earth, and exposure to higher levels of hazardous ionizing radiation. Preserving human health and performance in the face of these relentless hazards becomes progressively more difficult as missions increase in length and extend beyond low Earth orbit. Finding solutions is a significant challenge that is further complicated by logistical issues associated with studying these unique hazards. Although research studies using space-based platforms are the gold standard, these are not without limitations. Factors such as the small sample size of the available astronaut crew, high expense, and time constraints all add to the logistical challenge. To overcome these limitations, a wide variety of Earth-based analogs, from polar research outposts to an undersea laboratory, are available to augment space-based studies. Each analog simulates unique physiological and behavioral effects associated with spaceflight and, therefore, for any given study, the choice of an appropriate platform is closely linked to the phenomena under investigation as well as the characteristics of the analog. There are pros and cons to each type of analog and each actual facility, but overall they provide a reasonable means to overcome the barriers associated with conducting experimental research in space. Analogs, by definition, will never be perfect, but they are a useful component of an integrated effort to understand the human risks of living and working in space. They are a necessary resource for pushing the frontier of human spaceflight, both for astronauts and for commercial space activities. In this review, we describe the use of analogs here on Earth to replicate specific aspects of the spaceflight environment and highlight how analog studies support future human endeavors in space.

Medical countermeasures for radiation induced health effects: report of an Interagency Panel Session held at the NASA Human Research Program Investigator's Workshop, 26 January 2017.

An Interagency Panel Session organized by the NASA Human Research Program (HRP) Space Radiation Program Element (SRPE) was held during the NASA HRP Investigator's Workshop (IWS) in Galveston, Texas on 26 January 2017 to identify complementary research areas that will advance the testing and development of medical countermeasures (MCMs) in support of radioprotection and radiation mitigation on the ground and in space. There were several areas of common interest identified among the various participating agencies. This report provides a summary of the topics discussed by each agency along with potential areas of intersection for mutual collaboration opportunities. Common goals included repurposing of pharmaceuticals, nutraceuticals for use as radioprotectors and/or mitigators, low-dose/chronic exposure paradigms, late effects post-radiation exposure, mixed-field exposures of gamma-neutron, performance decrements, and methods to determine individual exposure levels.

NASA's first ground-based Galactic Cosmic Ray Simulator: Enabling a new era in space radiobiology research.

With exciting new NASA plans for a sustainable return to the moon, astronauts will once again leave Earth's protective magnetosphere only to endure higher levels of radiation from galactic cosmic radiation (GCR) and the possibility of a large solar particle event (SPE). Gateway, lunar landers, and surface habitats will be designed to protect crew against SPEs with vehicle optimization, storm shelter concepts, and/or active dosimetry; however, the ever penetrating GCR will continue to pose the most significant health risks especially as lunar missions increase in duration and as NASA sets its aspirations on Mars. The primary risks of concern include carcinogenesis, central nervous system (CNS) effects resulting in potential in-mission cognitive or behavioral impairment and/or late neurological disorders, degenerative tissue effects including circulatory and heart disease, as well as potential immune system decrements impacting multiple aspects of crew health. Characterization and mitigation of these risks requires a significant reduction in the large biological uncertainties of chronic (low-dose rate) heavy-ion exposures and the validation of countermeasures in a relevant space environment. Historically, most research on understanding space radiation-induced health risks has been performed using acute exposures of monoenergetic single-ion beams. However, the space radiation environment consists of a wide variety of ion species over a broad energy range. Using the fast beam switching and controls systems technology recently developed at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory, a new era in radiobiological research is possible. NASA has developed the "GCR Simulator" to generate a spectrum of ion beams that approximates the primary and secondary GCR field experienced at human organ locations within a deep-space vehicle. The majority of the dose is delivered from protons (approximately 65%-75%) and helium ions (approximately 10%-20%) with heavier ions (Z ≥ 3) contributing the remainder. The GCR simulator exposes state-of-the art cellular and animal model systems to 33 sequential beams including 4 proton energies plus degrader, 4 helium energies plus degrader, and the 5 heavy ions of C, O, Si, Ti, and Fe. A polyethylene degrader system is used with the 100 MeV/n H and He beams to provide a nearly continuous distribution of low-energy particles. A 500 mGy exposure, delivering doses from each of the 33 beams, requires approximately 75 minutes. To more closely simulate the low-dose rates found in space, sequential field exposures can be divided into daily fractions over 2 to 6 weeks, with individual beam fractions as low as 0.1 to 0.2 mGy. In the large beam configuration (60 × 60 cm2), 54 special housing cages can accommodate 2 to 3 mice each for an approximately 75 min duration or 15 individually housed rats. On June 15, 2018, the NSRL made a significant achievement by completing the first operational run using the new GCR simulator. This paper discusses NASA's innovative technology solution for a ground-based GCR simulator at the NSRL to accelerate our understanding and mitigation of health risks faced by astronauts. Ultimately, the GCR simulator will require validation across multiple radiogenic risks, endpoints, doses, and dose rates.

Galactic cosmic ray simulation at the NASA Space Radiation Laboratory.

Most accelerator-based space radiation experiments have been performed with single ion beams at fixed energies. However, the space radiation environment consists of a wide variety of ion species with a continuous range of energies. Due to recent developments in beam switching technology implemented at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL), it is now possible to rapidly switch ion species and energies, allowing for the possibility to more realistically simulate the actual radiation environment found in space. The present paper discusses a variety of issues related to implementation of galactic cosmic ray (GCR) simulation at NSRL, especially for experiments in radiobiology. Advantages and disadvantages of different approaches to developing a GCR simulator are presented. In addition, issues common to both GCR simulation and single beam experiments are compared to issues unique to GCR simulation studies. A set of conclusions is presented as well as a discussion of the technical implementation of GCR simulation.

Model predictions and visualization of the particle flux on the surface of Mars.

Model calculations of the particle flux on the surface of Mars due to the Galactic Cosmic Rays (GCR) can provide guidance on radiobiological research and shielding design studies in support of Mars exploration science objectives. Particle flux calculations for protons, helium ions, and heavy ions are reported for solar minimum and solar maximum conditions. These flux calculations include a description of the altitude variations on the Martian surface using the data obtained by the Mars Global Surveyor (MGS) mission with its Mars Orbiter Laser Altimeter (MOLA) instrument. These particle flux calculations are then used to estimate the average particle hits per cell at various organ depths of a human body in a conceptual shelter vehicle. The estimated particle hits by protons for an average location at skin depth on the Martian surface are about 10 to 100 particle-hits/cell/year and the particle hits by heavy ions are estimated to be 0.001 to 0.01 particle-hits/cell/year.