Initial State of Gap:

The space environment is variable with infrequent and sporadic solar particle events that consist largely of low to medium energy protons with energies up to a few hundred MeV. Acute radiation syndromes (ARS) from solar particle events (SPE) are of concern for manned spaceflight. ARS symptoms can include hematopoietic, gastrointestinal, cutaneous, and neurovascular decrements. However, through careful evaluation of SPE frequency and size probabilities, dose-rates, likely shielding conditions, and dose distribution at specific organs, the likelihood of acute risks is extremely small. There are scenarios, however, during lunar extravehicular activity (EVA), trans-lunar, or Mars transit where acute radiation sickness (ARS) may occur if adequate shielding is not available in a timely manner. The most probable ARS effects from SPE exposure during spaceflight that can potentially affect mis­sion success are the clinical symptoms associated with the prodromal phase. These symptoms of mild hematopoietic syndrome (nausea, vomiting, anorexia, and fatigue) occur within the first 48 hrs following exposure, along with skin injury and depression of the blood forming organs (BFOs).
 

NASA has established short-term dose limits (0.25 Gy-Eq to the BFO and 1.5 Gy-Eq to the skin in a 30-day period) to prevent clinically significant deterministic health effects, including performance decrements in flight. The short-term PELs are essential for mission planning and influence the amount of spacecraft shielding, storm shelter requirements, spacesuit design and timelines for EVAs and their accuracy is critical in order to ensure the health and safety of the astronaut crew.
 

Radiation protection must be provided in the form of shielding and operational dosimetry and monitoring. In addition, medical countermeasures may be necessary in the case of an unavoidable or accidental exposure when traveling outside of the protective magnet­osphere of Earth. Active dosimetry and predictive models support the evaluation of crew risks, operational requirements and decisions, and the efficient design of vehicle shelters to minimize exposures. NASA has developed state-of-the-art SPE models and radiation transport codes that can estimate SPE and galactic cosmic ray doses. These tools were reviewed by the National Research Council (NRC, 2012). The range of organ doses, real-time dosimetry systems, advanced space weather prediction and likely flight rules that will be required for deep space and lunar missions are under development by NASA.

The NSBRI Center for Space Radiation Research (CSRR) completed studies in 2017 examining proton RBEs at doses surrounding NASA’s Permissible Exposure Levels (PELs) for the BFO using rodent models. The CSRR also examined immune system effects, and synergies to the acute risk when combined with simulated microgravity. 

Ground-based research has resulted in preliminary estimates of proton RBEs and dose-rate modifiers for acute prodromal risks along with preliminary evidence for other spaceflight factors including immune response and simulated microgravity.  Studies are required to assess the accuracy of short-term limits to the BFO and the skin using proton energy distributions and dose-rates simulating an SPE. Studies should include assessment of the relative biological effectiveness (RBE) at lower energy below 10 MeV where protons become high-LET radiation. Research on acute risks related to EVA conditions must factor in the role of dose-rate over an EVA time course, the additional exposure IVA (intra-vehicular activity) for a terminated EVA, and other spaceflight factors that could modify expected dose response models for acute risks.

In addition, there is reasonable concern of a compromised immune system due to high skin doses from an SPE. This impact on the immune system may then increase the risk to the BFO. Therefore, studies addressing the biological effects of inhomogeneous dose distributions are required. Additional spaceflight factors such as weightlessness have also been shown to cause immune dysfunction and there is concern that this may also increase the risk to the BFO.

•Estimate RBE and dose-rate modifiers for acute radiation sickness components (nausea, vomiting, fatigue, blood kinetics).

•Determine the clinical spectrum and severity of skin damage from low energy protons and possible concomitant immune system response from skin doses and how this impacts the short term limits to the BFO.

•Determine the effect of simulated microgravity plus protons on acute radiation sickness and immune response.

Initial State of Gap:

The SRPE Risk Assessment Project has developed sophisticated nonlinear kinetics models of bone marrow stem cells and various blood system components to describe and provide accurate descriptions of human and other species responses to acute and chronic irradiation. These organ dose projection models are incorporated in a software package called ARRBOD and can be used by mission planners, radiation shield designers, space operations, and space biophysics researchers to assess clinically significant deterministic health effects including in-flight performance degradation from exposure to large SPEs. The ARRBOD model uses historical data from terrestrial exposures and requires model updates with radiobiological data specific to the space environment.  

Approach:

Ground-based, peer-reviewed research using appropriate animal models is needed to acquire data (see Acute Gap 1) to support refinement of acute radiation risk projection models with data specific to the space flight environment. Acute radiation response model updates will be made as radiobiological data is generated with proton exposures at historical SPE-relevant energies and dose rates including data on impact of inhomogeneous dose distributions that may occur with SPE exposures.  

• Acute Radiation Response Models updates with radiobiological data using space relevant proton energies, dose-rates, and total exposures possible during EVA’s.
• Acute Radiation Response Models model updates quantifying the interaction of skin, immune system and microgravity effects on the BFO and prodromal risks.

1. Initial State

   During SPEs, a variety of mission scenarios can require advanced monitoring technologies to assure proper operational responses to the dynamic radiation environment presented over the course of a SPE. Real-time area radiation monitors are utilized in spaceflight; however, further development is needed for active crew personnel dosimetry, including methods to incorporate dosimetry into extra-vehicular spacesuits or extravehicular activity (EVA) toolboxes. Spacesuits or vehicle radiation detectors will be constrained by mass, volume, power, and data transmission requirements.

2. Target for Closure:  Deliver  SPE alert and monitoring dosimetry technologies to the Advanced Exploration Systems (AES) program meeting the requirements specified in the Customer-Supplier Agreement between HRP and AES.
3. Interim Stages (Metrics)
   • Determine Dosimetry Requirements and Technology for EVA (20%)- completed.
   • Develop EVA Dosimetry (40%) – completed.
   • Develop EVA Alert Dosimetry (40%)-completed.
4. Approach

   Ground-based, peer-reviewed research to develop dosimetry systems for monitoring human exposures during spaceflight missions. Dosimeters that respond to variable dose-rates and within the LET range of an SPE are a priority.

   
   

1. Lunar EVA Dosimetry: Design of a Radiation Dosimeter for Astronauts During Lunar Extravehicular Activities – Completed and Prototype Delivered February 2012 (Borak, NSBRI)
2. Lunar EVA Dosimetry: Microdosimeter-Dosimeter Instrument- Delivery Milestone 06/30/2013 (Ziegler NSBRI)
3. Radiation Alert Immediate Disclosure (RAID) Delivery Milestone: 1/31/2014  (Krug, SBIR Phase II)

Delivery Milestones:

Lunar Dosimetry Requirements Ground Study (2007)

Spectroscopic Dosimeter (2010)

Tissue-Equivalent Radiation Dosimeter-On-A-Chip (2010)

Lunar EVA Dosimetry: Small Active Dosimetry System for Lunar Extravehicular Activity Missions: Spacesuit and Tool-Box Applications (4/2012)

1. Present state:
Closed. Transferred to Operations. Future work in this area will be performed by them.

2. Target for Closure: 

NASA has invested in shielding technologies for many years and understanding is nearly complete. Solar events can be shielded: HZETRN/BRYNTRN, NSRL-AGS experiments show polyethylene or water shielding are optimal materials. (Note, this is distinct from galactic cosmic ray exposure, which would require enormous mass to shield because of high energies and secondary radiation). ARRBOD model allows calculation of gender specific whole body effective dose for astronauts inside spacecraft, with specified shielding thickness, coupled with and probabilistic assessment of risk of acute radiation effects. ARRBOD and OLTARIS will be used for shielding assessments for future mission design as required.

3. Interim Stages (Metrics):

• Lunar Architecture Shielding Assessments – completed.
• Constellation Architecture Studies – completed.
• Future Exploration Architecture Studies -as required.

 4. Approach:

TASKS:

1)      Integrated Radiation Analysis and Design Tool Delivery Milestone: 3/31/2012  (Sandridge,  Direct)

2)      Patterns of Energy Deposition by HZE Particles in Cellular Targets Delivery Milestone: 10/30/2011 (Dingfelder SR NRA)

3)      Space Radiation Risk Assessment Project: Perform a comprehensive assessment of available acute radiation risk projection models, and t develop simulation software of acute risk for mission design assessments. Mission and Vehicle radiation analyses, as required

Delivery Milestones:

ESAS shielding analysis results to mission planners (2006)             

Lunar Architecture Shielding Assessments.    (2007)

Design Tool Inputs Received       (2007, 2008)

Acute Radiation Risk Body Organ Doses (ARRBOD) (9/2009)

Constellation Architecture Studies CAT (Data Analysis) (2010)

End-to-end mission radiation analysis     (2010)

Design Tool Inputs (2012)

ARRBOD model updates (2013, 2016)

Initial State of Gap:

Medical countermeasures (MCMs) under development for use in clinical practice and against radiological threats are expected to provide risk reduction for low-LET radiation and SPE radiation delivered at high doses and dose rates.  Common over-the-counter medications and regularly prescribed pharmaceuticals for anti-nausea and diarrhea are expected to ameliorate symptoms associated with prodromal syndrome.

Approach:

Ground-based research has resulted in preliminary evidence indicating that pharmaceutical agents developed for high dose gamma radiation may translate as medical countermeasures for hematopoietic acute radiation syndrome (H-ARS) due to SPE. Ground-based research using animal models to test medical countermeasures has provided additional evidence of risk reduction for H-ARS from solar particle event exposures using simulated SPE radiation and from successful studies with gamma exposure.  Additional studies in accordance with the FDA Animal Rule to validate the efficacy in a SPE-like environment will provide a greater level of confidence in countermeasure efficacy in humans.

Medical countermeasures for consideration will need to meet the requirements of the FDA Animal Rule to demonstrate safety and efficacy when human studies are not feasible.

Under the FDA Animal Rule:

The Animal Rule states that FDA will rely on evidence from animal studies to provide substantial evidence of effectiveness only when all of the following four criteria, quoted below, are met:

1. There is a reasonably well-understood pathophysiological mechanism of the toxicity of the substance and its prevention or substantial reduction by the product;

2. The effect is demonstrated in more than one animal species expected to react with a response predictive for humans, unless the effect is demonstrated in a single animal species that represents a sufficiently well-characterized animal model for predicting the response in humans;

3. The animal study endpoint is clearly related to the desired benefit in humans, generally the enhancement of survival or prevention of major morbidity; and

4. The data or information on the kinetics and pharmacodynamics of the product or other relevant data or information, in animals and humans, allows selection of an effective dose in humans.

If all of these criteria are met, it is reasonable to expect the efficacy of the drug in animals to be a reliable indicator of its effectiveness in humans.

Literature surveillance and technology watch activities will continue to identify new countermeasure drugs. Clinically-proven therapies or those currently being developed by the Biomedical Advanced Research and Development Authority (BARDA) and the National Institute of Health National Institute of Allergy and Infectious Diseases (NIH/NIAID) against acute effects from low-LET radiation exposure, as a result of nuclear disasters, may show effectiveness in the space environment. Chemopreventive agents being developed by the NIH National Cancer Institute (NIH/NCI) and tested in clinical trials may serve as candidates for radioprotection. Participation in multi-agency meetings and working groups will improve tech watch activities and allow for NASA to be aware of early stage product developments. 

• Identification and evaluation of select medical countermeasures to mitigate effects of acute radiation exposure.
• Determine administration protocol for medical countermeasures.
• Validate countermeasures to protect against H-ARS using space relevant radiation exposures and in accordance with the FDA Animal Rule.

Initial State of Gap:

The Risk Assessment Project has developed acute radiation risk models using a logistic scoring approach that is based on mathematical models of acute radiation syndromes developed by the Department of Defense coupled with solar particle event (SPE) predictive tools. There is a need to update these models with relative biological effectiveness (RBE) values specific to SPE-like protons and secondary radiations as new research data becomes available and to include additional models of SPE forecasting.

Acute Radiation Response Models will be modified to account for updates to RBE values as determined by research described in Gaps 1 and 2. SPE probabilistic modeling will be used as input to response models for overall risk assessment.  Collaboration with other NASA Programs will facilitate probabilistic SPE modeling efforts in terms of probability of occurrence and time scale of accumulated dose.  These models will be refined as necessary with updates to tools that can predict changes to the local space radiation environment including the probability of crew exposure levels and time to designated radiation shelter.

• Application of probabilistic risk assessments models to EVA + IVA scenarios for skin, blood forming organs (BFO) and other organs (Acute Radiation Response Models model updates).