Evaluating the risk of data loss due to particle radiation damage in a DNA data storage system.

DNA data storage is a potential alternative to magnetic tape for archival storage purposes, promising substantial gains in information density. Critical to the success of DNA as a storage media is an understanding of the role of environmental factors on the longevity of the stored information. In this paper, we evaluate the effect of exposure to ionizing particle radiation, a cause of data loss in traditional magnetic media, on the longevity of data in DNA data storage pools. We develop a mass action kinetics model to estimate the rate of damage accumulation in DNA strands due to neutron interactions with both nucleotides and residual water molecules, then utilize the model to evaluate the effect several design parameters of a typical DNA data storage scheme have on expected data longevity. Finally, we experimentally validate our model by exposing dried DNA samples to different levels of neutron irradiation and analyzing the resulting error profile. Our results show that particle radiation is not a significant contributor to data loss in DNA data storage pools under typical storage conditions.

Organ dose equivalents of albedo protons and neutrons under exposure to large solar particle events during lunar human landing missions.

Astronauts participating in lunar landing missions will encounter exposure to albedo particles emitted from the lunar surface as well as primary high-energy particles in the spectra of galactic cosmic rays (GCRs) and solar particle events (SPEs). While existing studies have examined particle energy spectra and absorbed doses in limited radiation exposure scenarios on and near the Moon, comprehensive research encompassing various shielding amounts and large SPEs on the lunar surface remains lacking. Additionally, detailed organ dose equivalents of albedo particles in a human model on the lunar surface have yet to be investigated. This work assesses the organ dose equivalents of albedo neutrons and albedo protons during historically large SPEs in August 1972 and September 1989 utilizing realistic computational anthropomorphic human phantom for the first time. Dosimetric quantities within human organs have been evaluated based on the PHITS Monte Carlo simulation results and quality factors of the state-of-the-art NASA Space Cancer Risk (NSCR) model, as well as ICRP publications. The results with the NSCR model indicate that the albedo contribution to organ dose equivalent is less than 3 % for 1 g/cm2 aluminum shielding, while it increases to more than 30 % in some organs for 50 g/cm2 aluminum shielding during exposure to low-energy-proton-rich SPEs.

Amplitude of One-Minute Fluctuations of Secondary Cosmic Rays as a Marker of Environmental Factor Determining Ultradian Rhythms in Body Temperature of Laboratory Rats.

The study examined association between oscillations of body temperature of laboratory Wistar rats maintained under constant illumination with the amplitude of fluctuations of secondary cosmic rays reported by neutron count rate provided by neutron monitors and geomagnetic undulations. In contrast to geomagnetic undulations, neutron count rate variations and body temperature oscillations in rats assessed by spectrum analysis of the corresponding step functions at 1-min intervals demonstrated almost permanent variations with the periods ranging from 100 to 400 min. Under conditions of constant illumination inducing changes in the period of circadian rhythm and predominance of the ultradian rhythms, an association between neutron count rate fluctuations and body temperature oscillations was observed perpetually during the day- and nighttime.

DNA damage response of haematopoietic stem and progenitor cells to high-LET neutron irradiation.

The radiosensitivity of haematopoietic stem and progenitor cells (HSPCs) to neutron radiation remains largely underexplored, notwithstanding their potential role as target cells for radiation-induced leukemogenesis. New insights are required for radiation protection purposes, particularly for aviation, space missions, nuclear accidents and even particle therapy. In this study, HSPCs (CD34+CD38+ cells) were isolated from umbilical cord blood and irradiated with 60Co γ-rays (photons) and high energy p(66)/Be(40) neutrons. At 2 h post-irradiation, a significantly higher number of 1.28 ± 0.12 γ-H2AX foci/cell was observed after 0.5 Gy neutrons compared to 0.84 ± 0.14 foci/cell for photons, but this decreased to similar levels for both radiation qualities after 18 h. However, a significant difference in late apoptosis was observed with Annexin-V+/PI+ assay between photon and neutron irradiation at 18 h, 43.17 ± 6.10% versus 55.55 ± 4.87%, respectively. A significant increase in MN frequency was observed after both 0.5 and 1 Gy neutron irradiation compared to photons illustrating higher levels of neutron-induced cytogenetic damage, while there was no difference in the nuclear division index between both radiation qualities. The results point towards a higher induction of DNA damage after neutron irradiation in HSPCs followed by error-prone DNA repair, which contributes to genomic instability and a higher risk of leukemogenesis.

Acute, Low-Dose Neutron Exposures Adversely Impact Central Nervous System Function.

A recognized risk of long-duration space travel arises from the elevated exposure astronauts face from galactic cosmic radiation (GCR), which is composed of a diverse array of energetic particles. There is now abundant evidence that exposures to many different charged particle GCR components within acute time frames are sufficient to induce central nervous system deficits that span from the molecular to the whole animal behavioral scale. Enhanced spacecraft shielding can lessen exposures to charged particle GCR components, but may conversely elevate neutron radiation levels. We previously observed that space-relevant neutron radiation doses, chronically delivered at dose-rates expected during planned human exploratory missions, can disrupt hippocampal neuronal excitability, perturb network long-term potentiation and negatively impact cognitive behavior. We have now determined that acute exposures to similar low doses (18 cGy) of neutron radiation can also lead to suppressed hippocampal synaptic signaling, as well as decreased learning and memory performance in male mice. Our results demonstrate that similar nervous system hazards arise from neutron irradiation regardless of the exposure time course. While not always in an identical manner, neutron irradiation disrupts many of the same central nervous system elements as acute charged particle GCR exposures. The risks arising from neutron irradiation are therefore important to consider when determining the overall hazards astronauts will face from the space radiation environment.

Celebrating 60 Years of Accomplishments of the Armed Forces Radiobiology Research Institute1.

Chartered by the U.S. Congress in 1961, the Armed Forces Radiobiology Research Institute (AFRRI) is a Joint Department of Defense (DoD) entity with the mission of carrying out the Medical Radiological Defense Research Program in support of our military forces around the globe. In the last 60 years, the investigators at AFRRI have conducted exploratory and developmental research with broad application to the field of radiation sciences. As the only DoD facility dedicated to radiation research, AFRRI's Medical Radiobiology Advisory Team provides deployable medical and radiobiological subject matter expertise, advising commanders in the response to a U.S. nuclear weapon incident and other nuclear or radiological material incidents. AFRRI received the DoD Joint Meritorious Unit Award on February 17, 2004, for its exceptionally meritorious achievements from September 11, 2001 to June 20, 2003, in response to acts of terrorism and nuclear/radiological threats at home and abroad. In August 2009, the American Nuclear Society designated the institute a nuclear historic landmark as the U.S.'s primary source of medical nuclear and radiological research, preparedness and training. Since then, research has continued, and core areas of study include prevention, assessment and treatment of radiological injuries that may occur from exposure to a wide range of doses (low to high). AFRRI collaborates with other government entities, academic institutions, civilian laboratories and other countries to research the biological effects of ionizing radiation. Notable early research contributions were the establishment of dose limits for major acute radiation syndromes in primates, applicable to human exposures, followed by the subsequent evolution of radiobiology concepts, particularly the importance of immune collapse and combined injury. In this century, the program has been essential in the development and validation of prophylactic and therapeutic drugs, such as Amifostine, Neupogen®, Neulasta®, Nplate® and Leukine®, all of which are used to prevent and treat radiation injuries. Moreover, AFRRI has helped develop rapid, high-precision, biodosimetry tools ranging from novel assays to software decision support. New drug candidates and biological dose assessment technologies are currently being developed. Such efforts are supported by unique and unmatched radiation sources and generators that allow for comprehensive analyses across the various types and qualities of radiation. These include but are not limited to both 60Co facilities, a TRIGA® reactor providing variable mixed neutron and γ-ray fields, a clinical linear accelerator, and a small animal radiation research platform with low-energy photons. There are five major research areas at AFRRI that encompass the prevention, assessment and treatment of injuries resulting from the effects of ionizing radiation: 1. biodosimetry; 2. low-level and low-dose-rate radiation; 3. internal contamination and metal toxicity; 4. radiation combined injury; and 5. radiation medical countermeasures. These research areas are bolstered by an educational component to broadcast and increase awareness of the medical effects of ionizing radiation, in the mass-casualty scenario after a nuclear detonation or radiological accidents. This work provides a description of the military medical operations as well as the radiation facilities and capabilities present at AFRRI, followed by a review and discussion of each of the research areas.

Chronic Low Dose Neutron Exposure Results in Altered Neurotransmission Properties of the Hippocampus-Prefrontal Cortex Axis in Both Mice and Rats.

The proposed deep space exploration to the moon and later to Mars will result in astronauts receiving significant chronic exposures to space radiation (SR). SR exposure results in multiple neurocognitive impairments. Recently, our cross-species (mouse/rat) studies reported impaired associative memory formation in both species following a chronic 6-month low dose exposure to a mixed field of neutrons (1 mGy/day for a total dose pf 18 cGy). In the present study, we report neutron exposure induced synaptic plasticity in the medial prefrontal cortex, accompanied by microglial activation and significant synaptic loss in the hippocampus. In a parallel study, neutron exposure was also found to alter fluorescence assisted single synaptosome LTP (FASS-LTP) in the hippocampus of rats, that may be related to a reduced ability to insert AMPAR into the post-synaptic membrane, which may arise from increased phosphorylation of the serine 845 residue of the GluA1 subunit. Thus, we demonstrate for the first time, that low dose chronic neutron irradiation impacts homeostatic synaptic plasticity in the hippocampal-cortical circuit in two rodent species, and that the ability to successfully encode associative recognition memory is a dynamic, multicircuit process, possibly involving compensatory changes in AMPAR density on the synaptic surface.

Whole body potassium as a biomarker for potassium uptake using a mouse model.

Potassium is known for its effect on modifiable chronic diseases like hypertension, cardiac disease, diabetes (type-2), and bone health. In this study, a new method, neutron generator based neutron activation analysis (NAA), was utilized to measure potassium (K) in mouse carcasses. A DD110 neutron generator based NAA assembly was used for irradiation.Thirty-two postmortem mice (n= 16 males and 16 females, average weight [Formula: see text] and [Formula: see text] g) were employed for this study. Soft-tissue equivalent mouse phantoms were prepared for the calibration. All mice were irradiated for 10 minutes, and the gamma spectrum with 42K was collected using a high efficiency, high purity germanium (HPGe) detector. A lead shielding assembly was designed and developed around the HPGe detector to obtain an improved detection limit. Each mouse sample was irradiated and measured twice to reduce uncertainty. The average potassium concentration was found to be significantly higher in males [Formula: see text] compared to females [Formula: see text]. We also observed a significant correlation between potassium concentration and the weight of the mice. The detection limit for potassium quantification with the NAA system was 46 ppm. The radiation dose to the mouse was approximately 56 [Formula: see text] mSv for 10-min irradiation. In conclusion, this method is suitable for estimating individual potassium concentration in small animals. The direct evaluation of total body potassium in small animals provides a new way to estimate potassium uptake in animal models. This method can be adapted later to quantify potassium in the human hand and small animals in vivo. When used in vivo, it is also expected to be a valuable tool for longitudinal assessment, kinetics, and health outcomes.

Analyses of cancer incidence and other morbidities in neutron irradiated B6CF1 mice.

The Department of Energy conduced ten large-scale neutron irradiation experiments at Argonne National Laboratory between 1972 and 1989. Using a new approach to utilize experimental controls to determine whether a cross comparison between experiments was appropriate, we amalgamated data on neutron exposures to discover that fractionation significantly improved overall survival. A more detailed investigation showed that fractionation only had a significant impact on the death hazard for animals that died from solid tumors, but did not significantly impact any other causes of death. Additionally, we compared the effects of sex, age first irradiated, and radiation fractionation on neutron irradiated mice versus cobalt 60 gamma irradiated mice and found that solid tumors were the most common cause of death in neutron irradiated mice, while lymphomas were the dominant cause of death in gamma irradiated mice. Most animals in this study were irradiated before 150 days of age but a subset of mice was first exposed to gamma or neutron irradiation over 500 days of age. Advanced age played a significant role in decreasing the death hazard for neutron irradiated mice, but not for gamma irradiated mice. Mice that were 500 days old before their first exposures to neutrons began dying later than both sham irradiated or gamma irradiated mice.

Machine learning methodology for high throughput personalized neutron dose reconstruction in mixed neutron + photon exposures.

We implemented machine learning in the radiation biodosimetry field to quantitatively reconstruct neutron doses in mixed neutron + photon exposures, which are expected in improvised nuclear device detonations. Such individualized reconstructions are crucial for triage and treatment because neutrons are more biologically damaging than photons. We used a high-throughput micronucleus assay with automated scanning/imaging on lymphocytes from human blood ex-vivo irradiated with 44 different combinations of 0-4 Gy neutrons and 0-15 Gy photons (542 blood samples), which include reanalysis of past experiments. We developed several metrics that describe micronuclei/cell probability distributions in binucleated cells, and used them as predictors in random forest (RF) and XGboost machine learning analyses to reconstruct the neutron dose in each sample. The probability of "overfitting" was minimized by training both algorithms with repeated cross-validation on a randomly-selected subset of the data, and measuring performance on the rest. RF achieved the best performance. Mean R2 for actual vs. reconstructed neutron doses over 300 random training/testing splits was 0.869 (range 0.761 to 0.919) and root mean squared error was 0.239 (0.195 to 0.351) Gy. These results demonstrate the promising potential of machine learning to reconstruct the neutron dose component in clinically-relevant complex radiation exposure scenarios.

Cancer incidence risks above and below 1 Gy for radiation protection in space.

The risk assessment quantities called lifetime attributable risk (LAR) and risk of exposure-induced cancer (REIC) are used to calculate the cumulative cancer incidence risks for astronauts, attributable to radiation exposure accumulated during long term lunar and Mars missions. These risk quantities are based on the most recently published epidemiological data on the Life Span Study (LSS) of Japanese A-bomb survivors, who were exposed to γ-rays and neutrons. In order to analyze the impact of a different neutron RBE on the risk quantities, a model for the neutron relative biological effectiveness (RBE) relative to gammas in the LSS is developed based on an older dataset with less follow-up time. Since both risk quantities are based on uncertain quantities, such as survival curves, and REIC includes deterministic radiation induced non-cancer mortality risks, modelled with data based on the general population, the risks for astronauts may not be optimally estimated. The suitability of these risk assessment measures for the use of cancer risk calculation for astronauts is discussed. The work presented here shows that the use of a higher neutron RBE than the value of 10, traditionally used in the LSS risk models, can reduce the risks up to almost 50%. Additionally, including an excess absolute risk (EAR) baseline scaling also increases the risks by between 0.4% and 8.1% for the space missions considered in this study. Using just an EAR model instead of an equally weighted EAR and excess relative risk (ERR) model can decrease the cumulative risks for the considered missions by between 0.4% and 4.1% if no EAR baseline scaling is applied. If EAR baseline scaling is included, the calculated risks with the EAR- and the mixed model, as well as the risks calculated with just the ERR model are almost identical and only small differences in the uncertainties are visible.

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.

Sleep fragmentation exacerbates executive function impairments induced by protracted low dose rate neutron exposure.

PURPOSE: Astronauts on the planned missions to Mars are expected to have to work more autonomously than on previous missions. Thus mission success may be influenced by the astronauts' ability to respond quickly to unexpected problems, processes that require several executive functions. The purpose of this study was to determine the impact that prolonged low dose and low dose rate exposure to neutrons had on two executive functions, and whether the severity and incidence of cognitive impairment was altered by sleep fragmentation. MATERIALS AND METHODS: In this study we assessed the impact that prolonged (six month) low dose rate neutron exposure had on the ability of male Wistar rats to perform in two executive function tasks (i.e. attentional set shifting (ATSET) - a constrained cognitive flexibility task and the UCFlex assay - an unconstrained cognitive flexibility task). In recognition of the fact that astronauts also have to contend with inadequate sleep quantity and quality for much of their time in space, we determined the impact that relatively mild sleep disruption had on the ability to perform in the ATSET test in sham and neutron-irradiated rats. RESULTS: Chronic low dose (18 cGy) and dose-rate (1 mGy/day) exposure of rats to mixed neutron and photon over the course of six months resulted in significant impairment of simple discrimination (SD) performance. Should similar effects occur in astronauts subjected to low dose rate exposure to Space Radiation, the impairment of SD performance would result in a decreased ability to identify and learn the 'rules' required to respond to a new task or situation. Analysis of the behavioral data by kernel density estimation revealed that 40% of rats had severe ATSET impairments. This value may be a best-case scenario because exposure to neutrons also adversely impacted performance in the UCFlex task. Furthermore, when the good performing rats were reevaluated after they had been subjected to sleep fragmentation, additional ATSET performance decrements were observed in the set shifting stages of the ATSET test, with only 7.4% of the neutron exposed rats able to successfully perform ATSET under normal and sleep fragmented conditions, as opposed to ∼55% of shams. CONCLUSION: Protracted low dose and low dose rate neutron exposures impairs executive functions in a high percentage of rats that were normally rested, however further detriments in performance become evident when the rats are subjected to sleep fragmentation.

A Systematic Review of the Hematopoietic Acute Radiation Syndrome (H-ARS) in Canines and Non-human Primates: Acute Mixed Neutron/Gamma vs. Reference Quality Radiations.

A systematic review of relevant studies that determined the dose response relationship (DRR) for the hematopoietic (H) acute radiation syndrome (ARS) in the canine relative to radiation quality of mixed neutron:gamma radiations, dose rate, and exposure uniformity relative to selected reference radiation exposure has not been performed. The datasets for rhesus macaques exposure to mixed neutron:gamma radiation are used herein as a species comparative reference to the canine database. The selection of data cohorts was made from the following sources: Ovid Medline (1957-present), PubMed (1954-present), AGRICOLA (1976-present), Web of Science (1954-present), and US HHS RePORT (2002-present). The total number of hits across all search sites was 3,077. Several referenced, unpublished, non-peer reviewed government reports were unavailable for review. Primary published studies using canines, beagles, and mongrels were evaluated to provide an informative and consistent review of mixed neutron:gamma radiation effects to establish the DRRs for the H-ARS. Secondary and tertiary studies provided additional information on the hematologic response or the effects on hematopoietic progenitor cells, radiation dosimetry, absorbed dose, and organ dose. The LD50/30 values varied with neutron quality, exposure aspect, and mixed neutron:gamma ratio. The reference radiation quality varied from 250 kVp or 1-2 MeV x radiation and Co gamma radiation. A summary of a published review of a data set describing the DRR in rhesus macaques for mixed neutron:gamma radiation exposure in the H-ARS is included for a comparative reference to the canine dataset. The available evidence provided a reliable and extensive database that characterized the DRR for the H-ARS in canines and young rhesus macaques exposed to mixed neutron:gamma radiations of variable energy relative to 250 kVp, 1-2 MeV x radiation and Co gamma, and uniform and non-uniform total-body irradiation without the benefit of medical management. The mixed neutron:gamma radiation showed an energy-dependent RBE of ~ 1.0 to 2.0 relative to reference radiation exposure within both species. A marginal database described the DRR for the gastrointestinal (GI)-ARS. Medical management showed benefit in both species relative to the mixed neutron:gamma as well as exposure to reference radiation. The DRR for the H-ARS was characterized by steep slopes and relative LD50/30 values that reflected the radiation quality, exposure aspect, and dose rate over a range in time from 1956-2012.

Investigation of neutron and gamma radiation protective characteristics of synthesized quinoline derivatives.

PURPOSE: Quinoline is formed by various natural compounds, such as alkaloids from the cinchona plant, which exhibit various biological activities, and is an important building material for the development of new drugs. Quinoline can be used in anti-radiation drug development but radiation interaction properties must be determined. MATERIAL AND METHODS: In this study, six types of synthesized quinoline derivatives were used. Fast neutron removal cross-section, mean free path, half value layer and transmission number were theoretically determined by using GEometry ANd Tracking 4 and FLUktuierende KAskade simulation codes for neutron shielding. Neutron dose absorption rates were determined using the 241Am-Be fast neutron source and the Canberra NP series portable BF3 gas proportional neutron detector. Gamma radiation shielding parameters were determined by using WinXCom and PSY-X/PSD software. Additionally, the genotoxic potentials of the derivatives were assessed by using the Ames/Salmonella bacterial reversion assay. RESULTS AND CONCLUSIONS: Neutron shielding parameters such as removal cross-section, mean free path, half value layer and transmission number were theoretically determined for fast neutrons. To determine neutron absorption capacity of quinoline derivatives, neutron absorption, experiments were conducted. In addition, gamma radiation shielding parameters were calculated such as the mean free path (MFP), mass attenuation coefficient (µt), half value thickness layer (HVL) and effective atomic number (Zeff) in the energy range of 0.015-15 MeV. The results of the all quinoline derivatives have excellent fast neutron shielding power compared to ordinary concrete. In addition, all quinoline derivatives have been found to have the capacity to attenuate gamma radiation. Moreover, they absorb well in both types of radiation, do not cause secondary radiation, and they are genotoxically safe at the tested concentrations. This study has demonstrated that these products can be used as active ingredients for a drug to be developed against radiation.

Prediction of radiation-induced malfunction for cardiac implantable electronic devices (CIEDs).

PURPOSE: Cardiac implantable electronic devices (CIEDs) were believed to possess a tolerance dose to malfunction during radiotherapy. Although recent studies have qualitatively suggested neutrons as a cause of malfunction, numerical understanding has not been reached. The purpose of this work is to quantitatively clarify the contribution of secondary neutrons from out-of-field irradiation to the malfunction of CIEDs as well as to deduce the frequency of malfunctions until completion of prostate cancer treatment as a typical case. MATERIALS AND METHODS: Measured data were gathered from the literature and were re-analyzed. Firstly, linear relationship for a number of malfunctions to the neutron dose was suggested by theoretical consideration. Secondly, the accumulated number of malfunctions of CIEDs gathered from the literature was compared with the prescribed dose, scattered photon dose, and secondary neutron dose for analysis of their correlation. Thirdly, the number of malfunctions during a course of prostate treatment with high-energy X-ray, passive proton, and passive carbon-ion beams was calculated while assuming the same response to malfunctions, where X-rays consisted of 6-MV, 10-MV, 15-MV, and 18-MV beams. Monte Carlo simulation assuming simple geometry was performed for the distribution of neutron dose from X-ray beams, where normalization factors were applied to the distribution so as to reproduce the empirical values. RESULTS: Linearity between risk and neutron dose was clearly found from the measured data, as suggested by theoretical consideration. The predicted number of malfunctions until treatment completion was 0, 0.02 ± 0.01, 0.30 ± 0.08, 0.65 ± 0.17, 0.88 ± 0.50, and 0.14 ± 0.04 when 6-MV, 10-MV, 15-MV, 18-MV, passive proton, and passive carbon-ion beams, respectively, were employed, where the single model response to a malfunction of 8.6 ± 2.1 Sv- 1 was applied. CONCLUSIONS: Numerical understanding of the malfunction of CIEDs has been attained for the first time. It has been clarified that neutron dose is a good scale for the risk of CIEDs in radiotherapy. Prediction of the frequency of malfunction as well as discussion of the risk to CIEDs in radiotherapy among the multiple modalities have become possible. Because the present study quantitatively clarifies the neutron contribution to malfunction, revision of clinical guidelines is suggested.

Monitoring Physiological Changes in Neutron-Exposed Normal Mouse Brain Using FDG-PET and DW-MRI.

We monitored a physiological response in a neutron-exposed normal mouse brain using two imaging tools, [18F]fluro-deoxy-D-glucose positron emission tomography ([18F]FDG-PET) and diffusion weighted-magnetic resonance imaging (DW-MRI), as an imaging biomarker. We measured the apparent diffusion coefficient (ADC) of DW-MRI and standardized uptake value (SUV) of [18F]FDG-PET, which indicated changes in the cellular environment for neutron irradiation. This approach was sensitive enough to detect cell changes that were not confirmed in hematoxylin and eosin (H&E) results. Glucose transporters (GLUT) 1 and 3, indicators of the GLUT capacity of the brain, were significantly decreased after neutron irradiation, demonstrating that the change in blood-brain-barrier (BBB) permeability affects the GLUT, with changes in both SUV and ADC values. These results demonstrate that combined imaging of the same object can be used as a quantitative indicator for in vivo pathological changes. In particular, the radiation exposure assessment of combined imaging, with specific integrated functions of [18F]FDG-PET and MRI, can be employed repeatedly for noninvasive analysis performed in clinical practice. Additionally, this study demonstrated a novel approach to assess the extent of damage to normal tissues as well as therapeutic effects on tumors.

Effects of chronic exposure to a mixed field of neutrons and photons on behavioral and cognitive performance in mice.

To simulate the space radiation environment astronauts are exposed to, most studies involve acute exposures but during a space mission there will be chronic (long-lasting) exposures. To address this knowledge gap, a neutron irradiator using a 252Cf (252Californium) source was used to generate a mixed field of neutrons and photons to simulate chronic, low dose rate exposures to high LET radiation. In the present study, we assessed the effects chronic neutron exposure starting at 60 days of age on behavioral and cognitive performance of BALB/c female and C3H male mice at 600 and 700 days of age as part of an opportunistic study that took advantage of the availability of neutron and sham-irradiated mice from a radiation carcinogenesis experiment. There were profound dose- and time point-dependent effects of chronic neutron exposure. At the 600-day time point, irradiated BALB/c female mice showed improved nest building at all three doses. At the 700-day, but not 600-day, time point slightly but significantly increased body weights were seen in C3H male mice exposed to 0.118 Gy. At the 600-day time point BALB/c female mice irradiated with 0.2 Gy did, like sham-irradiated, not show preferential exploration of the novel object that was seen in mice irradiated with 0.118 or 0.4 Gy. In C3H male mice exposed to 0.4 Gy and at the 600-day time point, increased measures of anxiety were observed on days 1 and 2 in the open field. Thus, different outcome measures show distinct dose-response relationships, with some anticipated to worsen performance during space missions, like increased measures of anxiety, while other anticipated to enhance performance, such as increased nest building and object recognition.

Neutron dose and its measurement in proton therapy-current State of Knowledge.

Proton therapy has shown dosimetric advantages over conventional radiation therapy using photons. Although the integral dose for patients treated with proton therapy is low, concerns were raised about late effects like secondary cancer caused by dose depositions far away from the treated area. This is especially true for neutrons and therefore the stray dose contribution from neutrons in proton therapy is still being investigated. The higher biological effectiveness of neutrons compared to photons is the main cause of these concerns. The gold-standard in neutron dosimetry is measurements, but performing neutron measurements is challenging. Different approaches have been taken to overcome these difficulties, for instance with newly developed neutron detectors. Monte Carlo simulations is another common technique to assess the dose from secondary neutrons. Measurements and simulations are used to develop analytical models for fast neutron dose estimations. This article tries to summarize the developments in the different aspects of neutron dose in proton therapy since 2017. In general, low neutron doses have been reported, especially in active proton therapy. Although the published biological effectiveness of neutrons relative to photons regarding cancer induction is higher, it is unlikely that the neutron dose has a large impact on the second cancer risk of proton therapy patients.

Transcriptomic responses in mouse blood during the first week after in vivo gamma irradiation.

Due to limitations of available human models for development of gene expression based radiation biodosimetry, many such studies have made use of mouse models. To provide a broad view of the gene expression response to irradiation in the mouse, we have exposed male C57BL/6 mice to 0, 1.5, 3, 6 or 10 Gy of gamma rays, sacrificing groups of the mice at 1, 2, 3, 5, or 7 days after exposure. We then profiled global gene expression in blood from individual mice using Agilent microarrays. In general, we found increasing numbers of genes differentially expressed with increasing dose, with more prolonged responses after the higher doses. Gene ontology analysis showed a similar pattern, with more biological processes enriched among the genes responding to higher doses, and at later times after exposure. Clustering the timecourse expression data using maSigPro identified four broad patterns of response, representing different gene ontology functions. The largest of these clusters included genes with initially decreased expression followed by increased expression at later times, a pattern of expression previously reported for several genes following neutron exposure. Another gene cluster showing consistent down regulation suggests genes useful for biodosimetry throughout the first week after exposure can be identified.