Design and dosimetry of a facility to study health effects following exposures to fission neutrons at low dose rates for long durations.

PURPOSE: During extended missions into deep space, astronauts will be exposed to a complex radiation field that includes high linear energy transfer (LET) radiation from high energy, heavy ions (HZE particles) at low dose rates of about 0.5 mGy/d for long durations. About 20% of the dose is delivered by ions with LET greater than 10 keV/µm. There are sparse empirical data in any species for carcinogenic effects from whole-body exposures to external sources of mixed or high LET radiation at this level of dose rates. For the induction of solid tumors, acute exposures to HZE ions have been shown to be substantially more effective per unit dose than low LET exposures associated with photons. To determine the health effects of high LET radiation at space-relevant dose rates on experimental animals, we developed a vivarium in which rodents could be irradiated with Californium (252Cf) neutrons for protracted periods of time. MATERIALS AND METHODS: The neutron source is a panoramic irradiator containing 252Cf located in a concrete shielded vault with a footprint of 53 m2. The vault can accommodate sufficient caging to simultaneously irradiate 900 mice and 60 rats for durations up to 400 d at a dose rate of 1 mGy/d and is approved for extended animal husbandry. RESULTS: The mixed field fluence is a combination of neutrons and photons emitted directly from the source and scattered particles from the concrete walls and floor. Mixed field dosimetry was performed using a miniature GM counter and CaF2:Dy thermoluminescent dosimeters (TLD) for photons and tissue-equivalent proportional counters (TEPC) for neutrons. TEPC data provided macroscopic dose rates as well as measurements of radiation quality based on lineal energy, y, and LET. The instantaneous dose rate from the source decreases with a half-life of 2.6 years. The exposure time is adjusted weekly to yield a total dose 1 mGy/d. The photon contribution is 20% of the total dose. The uncertainty in the delivered dose is estimated to be ±20% taking into account spatial variations in the room and random position of mice in each cage. The dose averaged LET for the charged particle recoil nuclei is 68 keV/µ. CONCLUSIONS: We have developed a facility to perform high LET studies in mice and rats at space relevant dose rates and career-relevant doses using neutrons emitted from the spontaneous fission of 252Cf.

New Concerns for Neurocognitive Function during Deep Space Exposures to Chronic, Low Dose-Rate, Neutron Radiation.

As NASA prepares for a mission to Mars, concerns regarding the health risks associated with deep space radiation exposure have emerged. Until now, the impacts of such exposures have only been studied in animals after acute exposures, using dose rates ∼1.5×105 higher than those actually encountered in space. Using a new, low dose-rate neutron irradiation facility, we have uncovered that realistic, low dose-rate exposures produce serious neurocognitive complications associated with impaired neurotransmission. Chronic (6 month) low-dose (18 cGy) and dose rate (1 mGy/d) exposures of mice to a mixed field of neutrons and photons result in diminished hippocampal neuronal excitability and disrupted hippocampal and cortical long-term potentiation. Furthermore, mice displayed severe impairments in learning and memory, and the emergence of distress behaviors. Behavioral analyses showed an alarming increase in risk associated with these realistic simulations, revealing for the first time, some unexpected potential problems associated with deep space travel on all levels of neurological function.

Spatial resolution requirements for active radiation detectors used beyond low earth orbit.

Measurements of the incident fluence of HZE particles, as a function of LET, are used to determine absorbed dose as well as Quality Factors for assigning risk estimates to astronauts during manned space missions. These data are often based on thin solid state detectors that measure energy deposition, dE, and the assumption that the trajectory of the particle, dx, is equivalent to the thickness of the detector. Heavy ions often fragment while penetrating shielding materials in vehicles or habitats. Projectile fragments can be clustered spatially and temporally at the location of the thin detector which are then misclassified as a single particle. Eliminating the confounding effects of coincident events is the first step in extending the reach of flight instruments to identify the charge and velocity of individual particles. Identification of individual particles, in a fragmentation spectrum, will require that detection systems have sufficient segmentation to eliminate coincident events. The objective of this study was to reduce coincident events while avoiding over-design and complexity. Monte Carlo simulations, using Geant4, were performed for 4He, 12C, 28Si and 56Fe ions at energies of 300, 900 and 2400 MeV/n incident upon aluminum shields having areal densities of 5.4, 13.5, and 54 g/cm2. The identity, energy and spatial distribution of all particles downstream from the shielding were analyzed using a novel approach based on proximity distributions. Results indicated that pixel dimensions on the order of 1 mm were sufficient to reduce errors caused by coincident events for active space radiation detectors.

Organ Doses to Airline Passengers Screened by X-Ray Backscatter Imaging Systems.

Advanced imaging technologies (AIT) are being developed for passenger airline transportation. They are designed to provide enhanced security benefits by identifying objects on passengers that would not be detected by methodologies now used for routine surveillance. X-ray backscatter imaging is one AIT system being considered. Since this technology is based on scanning passengers with ionizing radiation, concern has been raised relating to the health risks associated with these exposures. Recommendations for standards of radiation safety have been proposed by the American National Standards Institute published in ANSI/HPS N43.17-2009. A Monte Carlo based methodology for estimating organ doses received from an X-ray backscatter AIT system is presented. Radiological properties of a reference scanner including beam intensity, geometry and energy spectra were modeled based on previous studies and physical measurements. These parameters were incorporated into a Monte Carlo source subroutine and validated with comparison of simulated versus measured data. One extension of this study was to calculate organ and effective dose on a wide range of potential passengers. Computational phantoms with realistic morphologies were used including adults of 5th, 25th, 50th, 75th and 95th percentile weight, children of 5th, 50th and 95th percentile weight, and the developing fetus of 15, 25, and 38 weeks after conception. Additional sensitivity studies were performed to evaluate effects of passenger positioning within the scanner, energy spectrum and beam geometry, as well as failure mode analyses. Results for routine operations yielded a maximum effective dose to the adult and pediatric passengers of 15 and 25 nSv per screen, respectively. The developing fetus received a maximum organ dose and whole body dose of 16 nGy and 8.5 nGy per screen, respectively. The sensitivity analyses indicated that variations in positioning, energy spectra, and beam geometry yielded a range of effective doses per screen that were an order of magnitude below the ANSI recommendation.

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.

Neutron yields and effective doses produced by Galactic Cosmic Ray interactions in shielded environments in space.

In order to define the ranges of relevant neutron energies for the purposes of measurement and dosimetry in space, we have performed a series of Monte Carlo transport model calculations that predict the neutron field created by Galactic Cosmic Ray interactions inside a variety of simple shielding configurations. These predictions indicate that a significant fraction of the neutron fluence and neutron effective dose lies in the region above 20 MeV up to several hundred MeV. These results are consistent over thicknesses of shielding that range from very thin (2.7 g/cm(2)) to thick (54 g/cm(2)), and over both shielding materials considered (aluminum and water). In addition to these results, we have also investigated whether simplified Galactic Cosmic Ray source terms can yield predictions that are equivalent to simulations run with a full GCR source term. We found that a source using a GCR proton and helium spectrum together with a scaled oxygen spectrum yielded nearly identical results to a full GCR spectrum, and that the scaling factor used for the oxygen spectrum was independent of shielding material and thickness. Good results were also obtained using a GCR proton spectrum together with a scaled helium spectrum, with the helium scaling factor also independent of shielding material and thickness. Using a proton spectrum alone was unable to reproduce the full GCR results.

Description and verification of an algorithm for obtaining microdosimetric quantities for high-LET radiation using a single TEPC without pulse height analysis.

Microdosimetric spectra of single event distributions have been used to provide estimates of quality factors for radiation protection of high-LET radiation. In situations with high-dose rates it becomes difficult to measure, record and store energy deposition from single events. An alternative approach is to store random energy deposition events in a sequence of fixed time intervals that does not require identifying from single events. This can be accomplished with a single detector without pulse height analysis. We show the development of the algorithm using expectation analysis of the statistical estimators for moments of lineal energy: ȳf and ȳD. The method was tested using Monte Carlo simulations based on single event distributions measured with spherical tissue equivalent proportional counters where the event sizes spanned more than two orders of magnitude. The evaluation included testing at various mean numbers of events per interval (i.e., dose rate) and numbers of intervals (i.e., total duration). Results of the expectation analysis and Monte Carlo simulation showed that the algorithm corrects for the excess dispersion due to the random number of events in each time interval when the underlying dose rate is constant. It also converges to the correct value when there is a linear trend in dose rate of the duration of the measurement process. Although this system is not applicable for pulsed radiation fields it proved to be robust when applied to measured distributions with single event spectra (PuBe neutrons, Fe ions at 1,000 MeV/nucleon and a power function distribution of single event sizes) with a coefficient of variation of 25% for estimates of ȳD using 100 sampling intervals and 10% using 400 sampling intervals.

Quality factors for space radiation: A new approach.

NASA has derived new models for radiological risk assessment based on epidemiological data and radiation biology including differences in Relative Biological Effectiveness for leukemia and solid tumors. Comprehensive approaches were used to develop new risk cross sections and the extension of these into recommendations for risk assessment during space missions. The methodology relies on published data generated and the extensive research initiative managed by the NASA Human Research Program (HRP) and reviewed by the National Academy of Sciences. This resulted in recommendations for revised specifications of quality factors, QNASA(Z,ß) in terms of track structure concepts that extend beyond LET alone. The new paradigm for quality factors placed demands on radiation monitoring procedures that are not satisfied by existing dosimetry systems or particle spectrometers that are practical for space exploration where mass, volume, band width and power consumption are highly constrained. We have proposed a new definition of quality factors that relaxes the requirements for identifying charge, Z, and velocity, ß, of the incident radiation while still preserving the functional form of the inherent risk functions. The departure from the exact description of QNASA(Z,ß) is that the revised values are new functions of LET for solid cancers and leukemia. We present the motivation and process for developing the revised quality factors. We describe results of extensive simulations using GCR distributions in free space as well as the resulting spectra of primary and secondary particles behind aluminum shields and penetration through water. In all cases the revised dose averaged quality factors agreed with those based on the values obtained using QNASA(Z,ß). This provides confidence that emerging technologies for space radiation dosimetry can provide real time measurements of dose and dose equivalent while satisfying constraints on size, mass, power and bandwidth. The revised quality factors are sufficiently generalized to be applicable to radiation protection practices beyond space exploration.

Heavy charged particle radiobiology: using enhanced biological effectiveness and improved beam focusing to advance cancer therapy.

Ionizing radiation causes many types of DNA damage, including base damage and single- and double-strand breaks. Photons, including X-rays and γ-rays, are the most widely used type of ionizing radiation in radiobiology experiments, and in radiation cancer therapy. Charged particles, including protons and carbon ions, are seeing increased use as an alternative therapeutic modality. Although the facilities needed to produce high energy charged particle beams are more costly than photon facilities, particle therapy has shown improved cancer survival rates, reflecting more highly focused dose distributions and more severe DNA damage to tumor cells. Despite early successes of charged particle radiotherapy, there is room for further improvement, and much remains to be learned about normal and cancer cell responses to charged particle radiation.

Skyshine radiation resulting from 6 MV and 10 MV photon beams from a medical accelerator.

Skyshine radiation scattered in the atmosphere above a radiation therapy accelerator facility can result in measurable dose rates at locations near the facility on the ground and at roof level. A Reuter Stokes RSS-120 pressurized ion chamber was used to measure exposure rates in the vicinity of a Varian Trilogy Linear Accelerator at the Colorado State University Veterinary Medical Center. The linear accelerator was used to deliver bremsstrahlung photons from 6 MeV and 10 MeV electron beams with several combinations of field sizes and gantry angles. An equation for modeling skyshine radiation in the vicinity of medical accelerators was published by the National Council on Radiation Protection and Measurements in 2005. However, this model did not provide a good fit to the observed dose rates at ground level or on the roof. A more accurate method of estimating skyshine may be to measure the exposure rate of the radiation exiting the roof of the facility and to scale the results using the graphs presented in this paper.

Radiation leukemogenesis in mice: loss of PU.1 on chromosome 2 in CBA and C57BL/6 mice after irradiation with 1 GeV/nucleon 56Fe ions, X rays or gamma rays. Part I. Experimental observations.

Since deletion of the PU.1 gene on chromosome 2 is a crucial acute myeloid leukemia (AML) initiating step in the mouse model, we quantified PU.1 deleted cells in the bone marrow of gamma-, X- and 56Fe-ion-irradiated mice at various times postirradiation. Although 56Fe ions were initially some two to three times more effective than X or gamma rays in inducing PU.1 deletions, by 1 month postirradiation, the proportions of cells with PU.1 deletions were similar for the HZE particles and the sparsely ionizing radiations. These results indicate that while 56Fe ions are more effective in inducing PU.1 deletions, they are also more effective in causing collateral damage that removes hit cells from the bone marrow. After X, gamma or 56Fe-ion irradiation, AML-resistant C57BL/6 mice have fewer cells with PU.1 deletions than CBA mice, and those cells do not persist in the bone marrow of the C57B6/6 mice. Our findings suggest that quantification of PU.1 deleted bone marrow cells 1 month postirradiation can be used as surrogate for the incidence of radiation-induced AML measured in large-scale mouse studies. If so, PU.1 loss could be used to systematically assess the potential leukemogenic effects of other ions and energies in the space radiation environment.

Radiation leukemogenesis in mice: loss of PU.1 on chromosome 2 in CBA and C57BL/6 mice after irradiation with 1 GeV/nucleon 56Fe ions, X rays or gamma Rays. Part II. Theoretical considerations based on microdosimetry and the initial induction of chromosome aberrations.

Chromosome aberrations in mitotic bone marrow cells of CBA/Ca and C57BL/6 mice were measured 1 day after exposure to 1 Gy of 1 GeV/nucleon 56Fe ions or 3 Gy of gamma rays. The proportion that have lost a region of chromosome 2 containing the PU.1 gene could be explained by a model based on these measurements. The distribution of aberrations among cells was close to the expected Poisson for the gamma-irradiated cells, but for the HZE 56Fe ions the distribution was highly dispersed. The observations were consistent with the results of an analysis similar to that of Edwards and co-workers in 1980 after ex vivo irradiation of human blood with alpha particles. The analysis used to fit the current data was based on a compound Poisson process, also used previously by others, but in addition included the random nature of parameters involved such as cell nuclear diameter, particle traversal lengths through cell nuclei, production of aberrations, and cell cycle arrest per traversal. From the measured numbers of acentric fragments produced, the relative size of chromosome 2 and the region associated with PU.1 deletions, an independent prediction of PU.1 loss agreed well with measurements described in the accompanying paper.

A comparison of the measured responses of a tissue-equivalent proportional counter to high energy heavy (HZE) particles and those simulated using the Geant4 Monte Carlo code.

Monte Carlo simulations of heavy ion interactions using the Geant4 toolkit were compared with measurements of energy deposition in a spherical tissue-equivalent proportional counter (TEPC). A spherical cavity with a physical diameter of 12.7 mm was filled with propane-based tissue-equivalent gas surrounded by a wall of A-150 tissue-equivalent plastic that was 2.54 mm to thick. Measurements and Monte Carlo simulations were used to record the energy deposition and the trajectory of the incident particle on an event-by-event basis for ions ranging in atomic number from 2 ((4)He) to 26 ((56)Fe) and in energy from 200 MeV/nucleon to 1000 MeV/nucleon. In the simulations, tracking of secondary electrons was terminated when the range of an electron was below a specified threshold. The effects of range cuts for electrons at 0.5 µm, 1 µm, 10 µm, and 100 µm were evaluated. To simulate an energy deposition influenced by large numbers of low energy electrons with large transverse momentum, it was necessary to track electrons down to range cuts of 10 µm or less. The Geant4 simulated data closely matched the measured data acquired using a TEPC for incident particles traversing the center of the detector as well as near the gas-wall interface. Values of frequency mean lineal energy and dose mean lineal energy were within 8% of the measured data. The production of secondary particles in the aluminum vacuum chamber had no effect on the response of the TEPC for (56)Fe at 1000 MeV/nucleon. The results of this study confirm that Geant4 can simulate patterns of energy deposition for existing microdosimeters and is valuable for improving the design of a new generation of detectors used for space dosimetry and for characterizing particle beams used in hadron radiotherapy.

The response of a spherical tissue-equivalent proportional counter to different heavy ions having similar velocities.

A tissue-equivalent proportional counter (TEPC) has been used as a dosimeter in mixed radiation fields. Since it does not measure LET directly, the response function must be characterized in order to estimate quality factor and thus equivalent dose for the incident radiation. The objectives of this study were to measure the response of a spherical TEPC for different high-energy heavy ions (HZE) having similar velocity and to determine how quality factors can be determined. Data were obtained at the HIMAC heavy ion accelerator for (4)He and (12)C at 220 +/- 5 MeV/nucleon (beta = 0.59) and (12)C, (16)O, (28)Si and (56)Fe at 376 +/- 15 MeV/nucleon (beta = 0.70). A particle spectrometer recorded the charge and position of each incident beam particle. Events with low energy deposition were observed for particles that passed through the wall of the TEPC but not through the sensitive volume. The frequency averaged lineal energy, y(f), was always less than the LET of the incident particles. The dose averaged lineal energy, y(D), was approximately equal to LET for particles with LET greater than 10 keV/mum, whereas y(D) was larger than LET for the lighter particles with lower LET. Part of this effect is due to detector resolution and energy straggling that increases the variance of the response function. Although the TEPC is not a LET spectrometer, it can provide real time measurements of dose and provide estimates of quality factors for HZE particles using averaged values of lineal energy.

The response of a spherical tissue-equivalent proportional counter to different ions having similar linear energy transfer.

The response of a tissue-equivalent proportional counter (TEPC) to different ions having a similar linear energy transfer (LET) has been studied. Three ions, 14N, 20Ne and 28Si, were investigated using the HIMAC accelerator at the National Institute of Radiological Sciences at Chiba, Japan. The calculated linear energy transfer (LET( infinity )) of all ions was 44 +/- 2 keV/microm at the sensitive volume of the TEPC. A particle spectrometer was used to record the charge and position of each incident beam particle. This enabled reconstruction of the location of the track as it passed though the TEPC and ensured that the particle survived without fragmentation. The spectrum of energy deposition events in the TEPC could be evaluated as a function of trajectory through the TEPC. The data indicated that there are many events from particles that did not pass through the sensitive volume. The fraction of these events increased as the energy of the particle increased due to changes in the maximum energy of the delta rays. Even though the LET of the incident particles was nearly identical, the frequency-averaged lineal energy, y(F), as well as the dose-averaged lineal energy, y(D), varied with the velocity of the incident particle. However, both values were within 15% of LET in all cases.

Quality factors for alpha particles emitted in tissue.

A concept of a mean or dose averaged quality factor was defined in ICRP Publication 26 using relationships for quality factor as a function of LET. The concept of radiation weighting factors, wR, was introduced in ICRP Publication 60 in 1990. These are meant to be generalized factors that modify absorbed dose to reflect the risk of stochastic effects as a function of the quality of the radiation incident on the body or emitted by radioactivity within the body. The values of wr are equal to 20 for all alpha particles externally or internally emitted. This note compares the dose averaged quality factor for alpha particles originating in tissue using the old and revised recommendations for quality factor as a function of LET. The dose averaged quality factor never exceeds 20 using the old recommendations and is never less than 20 with the revised recommendations.