Light flashes and other sensory illusions perceived in space travel and on ground, including proton and heavy ion therapies.

Most of the astronauts experience visual illusions, apparent flashes of light (LF) in absence of light. The first reported observation of this phenomenon was in July 1969 by Buzz Aldrin, in the debriefing following the Apollo 11 mission. Several ground-based experiments in the 1970s tried to clarify the mechanisms behind these light flashes and to evaluate possible related risks. These works were supported by dedicated experiments in space on the following Apollo flights and in Low Earth Orbit (LEO). It was soon demonstrated that the LF could be caused by charged particles (present in the space radiation) traveling through the eye, and, possibly, some other visual cortical areas. In the 1990s the interest in these phenomena increased again and additional experiments in Low Earth Orbit and others ground-based were started. Recently patients undergoing proton and heavy ion therapy for eye or head and neck tumors have reported the perception of light flashes, opening a new channel to investigate these phenomena. In this paper the many LF studies will be reviewed, presenting an historical and scientific perspective consistent with the combined set of observations, offering a single comprehensive summary aimed to provide further insights on these phenomena. While the light flashes appear not to be a risk by themselves, they might provide information on the amount of radiation induced radicals in the astronauts' eyes. Understanding their generation mechanisms might also support radiation countermeasures development. However, even given the substantial progress outlined in this paper, many questions related to their generation are still under debate, so additional studies are suggested. Finally, it is also conceivable that further LF investigations could provide evidence about the possible interaction of single particles in space with brain function, impacting with the crew ability to optimally perform a mission.

LIDAL, a Time-of-Flight Radiation Detector for the International Space Station: Description and Ground Calibration.

LIDAL (Light Ion Detector for ALTEA, Anomalous Long-Term Effects on Astronauts) is a radiation detector designed to measure the flux, the energy spectra and, for the first time, the time-of-flight of ions in a space habitat. It features a combination of striped silicon sensors for the measurement of deposited energy (using the ALTEA device, which operated from 2006 to 2012 in the International Space Station) and fast scintillators for the time-of-flight measurement. LIDAL was tested and calibrated using the proton beam line at TIFPA (Trento Institute for Fundamental Physics Application) and the carbon beam line at CNAO (National Center for Oncology Hadron-therapy) in 2019. The performance of the time-of-flight system featured a time resolution (sigma) less than 100 ps. Here, we describe the detector and the results of these tests, providing ground calibration curves along with the methodology established for processing the detector's data. LIDAL was uploaded in the International Space Station in November 2019 and it has been operative in the Columbus module since January 2020.

EEG in extreme conditions: An advanced analysis pipeline for the human electroencephalographic signals recorded in space during the ALTEA experiment.

The Anomalous Long Term Effects in Astronauts (ALTEA) project originally aimed at disentangling the mechanisms behind astronauts' perception of light flashes. To this end, an experimental apparatus was set up in order to concurrently measure the tracks of cosmic radiation particles in the astronauts' head and the electroencephalographic (EEG) signals generated by their brain. So far, the ALTEA data set has never been analyzed with the broader intent to study possible interference between cosmic radiation and the brain, regardless of light flashes. The aim of this work is to define a pipeline to systematically pre-process the ALTEA EEG data. Compared to the analysis of standard EEG recording, this task is made more difficult by the presence of unconventional artifacts due to the extreme recording conditions that, in particular, require the EEG cap to be positioned next to another noisy electronic device, namely the particle detectors. Here we show how standard tools for the analysis of EEG data can be tuned to deal with these unconventional artifacts. After pre-processing the available data we were able to elucidate a shift of the center frequency of the α rhythm induced by visual stimulation, thus proving the effectiveness of the implemented pipeline. This work represents the first study presenting results of signal processing of ALTEA EEG time series. Further, it is the starting point of a future work aimed at analyzing the interaction between EEG and cosmic radiation.

Towards sustainable human space exploration-priorities for radiation research to quantify and mitigate radiation risks.

Human spaceflight is entering a new era of sustainable human space exploration. By 2030 humans will regularly fly to the Moon's orbit, return to the Moon's surface and preparations for crewed Mars missions will intensify. In planning these undertakings, several challenges will need to be addressed in order to ensure the safety of astronauts during their space travels. One of the important challenges to overcome, that could be a major showstopper of the space endeavor, is the exposure to the space radiation environment. There is an urgent need for quantifying, managing and limiting the detrimental health risks and electronics damage induced by space radiation exposure. Such risks raise key priority topics for space research programs. Risk limitation involves obtaining a better understanding of space weather phenomena and the complex radiation environment in spaceflight, as well as developing and applying accurate dosimetric instruments, understanding related short- and long-term health risks, and strategies for effective countermeasures to minimize both exposure to space radiation and the remaining effects post exposure. The ESA/SciSpacE Space Radiation White Paper identifies those topics and underlines priorities for future research and development, to enable safe human and robotic exploration of space beyond Low Earth Orbit.

Radiation environment in exploration-class space missions and plants' responses relevant for cultivation in Bioregenerative Life Support Systems.

For deep space exploration, radiation effects on astronauts, and on items fundamental for life support systems, must be kept under a pre-agreed threshold to avoid detrimental outcomes. Therefore, it is fundamental to achieve a deep knowledge on the radiation spatial and temporal variability in the different mission scenarios as well as on the responses of different organisms to space-relevant radiation. In this paper, we first consider the radiation issue for space exploration from a physics point of view by giving an overview of the topics related to the spatial and temporal variability of space radiation, as well as on measurement and simulation of irradiation, then we focus on biological issues converging the attention on plants as one of the fundamental components of Bioregenerative Life Support Systems (BLSS). In fact, plants in BLSS act as regenerators of resources (i.e. oxygen production, carbon dioxide removal, water and wastes recycling) and producers of fresh food. In particular, we summarize some basic statements on plant radio-resistance deriving from recent literature and concentrate on endpoints critical for the development of Space agriculture. We finally indicate some perspective, suggesting the direction future research should follow to standardize methods and protocols for irradiation experiments moving towards studies to validate with space-relevant radiation the current knowledge. Indeed, the latter derives instead from experiments conducted with different radiation types and doses and often with not space-oriented scopes.

Novel Algorithm for Radon Real-Time Measurements with a Pixelated Detector.

Nowadays, radon gas exposure is considered one of the main health concerns for the population because, by carrying about half the total dose due to environmental radioactivity, it is the second cause of lung cancer after smoking. Due to a relatively long half-life of 3.82 days, the chemical inertia and since its parent Ra-226 is largely diffuse on the earth's crust and especially in the building materials, radon can diffuse and potentially saturate human habitats, with a concentration that can suddenly change during the 24 h day depending on temperature, pressure, and relative humidity. For such reasons, 'real-time' measurements performed by an active detector, possibly of small dimensions and a handy configuration, can play an important role in evaluating the risk and taking the appropriate countermeasures to mitigate it. In this work, a novel algorithm for pattern recognition was developed to exploit the potentialities of silicon active detectors with a pixel matrix structure to measure radon through the α emission, in a simple measurement configuration, where the device is placed directly in air with no holder, no collection filter or electrostatic field to drift the radon progenies towards the detector active area. This particular measurement configuration (dubbed as bare) requires an α/ß-discrimination method that is not based on spectroscopic analysis: as the gas surrounds the detector the α particles are emitted at different distances from it, so they lose variable energy amount in air depending on the traveled path-length which implies a variable deposited energy in the active area. The pixels matrix structure allows overcoming this issue because the interaction of α, ß and γ particles generate in the active area of the detector clusters (group of pixels where a signal is read) of different shape and energy dispersion. The novel algorithm that exploits such a phenomenon was developed using a pixelated silicon detector of the TimePix family with a compact design. An α (Am-241) and a ß (Sr-90) source were used to calibrate the algorithm and to evaluate its performances in terms of ß rejection capability and α recognition efficiency. Successively, the detector was exposed to different radon concentrations at the ENEA-INMRI radon facility in 'bare' configuration, in order to check the linearity of the device response over a radon concentration range. The results for this technique are presented and discussed, highlighting the potential applications especially the possibility to exploit small and handy detectors to perform radon active measurements in the simplest configuration.

An easy-to-use function to assess deep space radiation in human brains.

Health risks from radiation exposure in space are an important factor for astronauts' safety as they venture on long-duration missions to the Moon or Mars. It is important to assess the radiation level inside the human brain to evaluate the possible hazardous effects on the central nervous system especially during solar energetic particle (SEP) events. We use a realistic model of the head/brain structure and calculate the radiation deposit therein by realistic SEP events, also under various shielding scenarios. We then determine the relation between the radiation dose deposited in different parts of the brain and the properties of the SEP events and obtain some simple and ready-to-use functions which can be used to quickly and reliably forecast the event dose in the brain. Such a novel tool can be used from fast nowcasting of the consequences of SEP events to optimization of shielding systems and other mitigation strategies of astronauts in space.

Multiple sensory illusions are evoked during the course of proton therapy.

Visual illusions from astronauts in space have been reported to be associated with the passage of high energy charged particles through visual structures (retina, optic nerve, brain). Similar effects have also been reported by patients under proton and heavy ion therapies. This prompted us to investigate whether protons at the Loma Linda University Proton Therapy and Research Center (PTRC) may also affect other sensory systems beside evoking similar perceptions on the visual system. A retrospective review of proton radiotherapy patient records at PTRC identified 29 sensory reports from 19 patients who spontaneously reported visual, olfactory, auditory and gustatory illusions during treatment. Our results suggest that protons can evoke neuronal responses sufficient to elicit conscious sensory illusion experiences, in four senses (auditory, taste, smell, and visual) analogous to those from normal sensory inputs. The regions of the brain receiving the highest doses corresponded with the anatomical structures associated with each type of illusion. Our findings suggest that more detailed queries about sensory illusions during proton therapy are warranted, possibly integrated with quantitative effect descriptions (such as electroencephalography) and can provide additional physiological basis for understanding the effects of protons on central nervous system tissues, needed for radiation risk assessment in advance of deep space human exploration.

Calculation of dose distribution in a realistic brain structure and the indication of space radiation influence on human brains.

One of the most important steps in the near-future space age will be a crew mission returning to the Moon and even a manned mission to Mars. Unfortunately, such a mission will expose astronauts to unavoidable cosmic radiation in deep space and on the Martian or lunar surface. Thus, a better understanding of the radiation environment for such a mission and the consequent biological impacts on humans, in particular the human brains, is critical. The need for this better understanding is strongly suggested by investigations on animal models and on human patients who were undergoing irradiation for cancer therapy in the head. These have revealed unexpected alterations in the central nervous system behavior and sensitivity of mature neurons in the brain to charged particles. However, such experiments shall not be carried out realistically in space using humans. Therefore, to investigate the impact of cosmic radiation on human brains and the potential influence on the brain functions, we model and study the cosmic particle-induced radiation dose in a realistic head structure. Specifically speaking, 134 slices of computed tomography (CT) images of an actual human head have been used as a 3D phantom in Geant4 (GEometry ANd Tracking), which is a Monte Carlo tool for simulating energetic particles impinging into different parts of the brain and deliver radiation dose therein. As a first step, we compare the influence of different brain structures (e.g., with or without bones, with or without soft tissues) to the resulting dose therein to demonstrate the necessity of using a realistic brain structure for our investigation. Afterward, we calculate energy-dependent functions of dose distribution, for the most important (some of the most abundant and most biologically-relevant) particle types encountered during a deep space mission inside a spacecraft or habitat such as protons, helium ions, neutrons and some major heavier ions like carbon, nitrogen, and iron particles. Furthermore, two different scenarios have been modeled as a comparison: a human head without shielding protection and a human head with an aluminum shielding shell around (of varying thickness). These functions can then be used to fold with energetic cosmic-ray particle spectra of the ambient environment for obtaining the dose rate distribution at different lobes of the human brain. Our calculation of these functions can serve as a ready tool and a baseline for further evaluations of the radiation in the brain encountered during a space mission with different radiation fields, such as on the surface of the Moon or Mars.

Performances of Kevlar and Polyethylene as radiation shielding on-board the International Space Station in high latitude radiation environment.

Passive radiation shielding is a mandatory element in the design of an integrated solution to mitigate the effects of radiation during long deep space voyages for human exploration. Understanding and exploiting the characteristics of materials suitable for radiation shielding in space flights is, therefore, of primary importance. We present here the results of the first space-test on Kevlar and Polyethylene radiation shielding capabilities including direct measurements of the background baseline (no shield). Measurements are performed on-board of the International Space Station (Columbus modulus) during the ALTEA-shield ESA sponsored program. For the first time the shielding capability of such materials has been tested in a radiation environment similar to the deep-space one, thanks to the feature of the ALTEA system, which allows to select only high latitude orbital tracts of the International Space Station. Polyethylene is widely used for radiation shielding in space and therefore it is an excellent benchmark material to be used in comparative investigations. In this work we show that Kevlar has radiation shielding performances comparable to the Polyethylene ones, reaching a dose rate reduction of 32 ± 2% and a dose equivalent rate reduction of 55 ± 4% (for a shield of 10 g/cm2).

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.

Radiation Measurements Performed with Active Detectors Relevant for Human Space Exploration.

A reliable radiation risk assessment in space is a mandatory step for the development of countermeasures and long-duration mission planning in human spaceflight. Research in radiobiology provides information about possible risks linked to radiation. In addition, for a meaningful risk evaluation, the radiation exposure has to be assessed to a sufficient level of accuracy. Consequently, both the radiation models predicting the risks and the measurements used to validate such models must have an equivalent precision. Corresponding measurements can be performed both with passive and active devices. The former is easier to handle, cheaper, lighter, and smaller but they measure neither the time dependence of the radiation environment nor some of the details useful for a comprehensive radiation risk assessment. Active detectors provide most of these details and have been extensively used in the International Space Station. To easily access such an amount of data, a single point access is becoming essential. This review presents an ongoing work on the development of a tool that allows obtaining information about all relevant measurements performed with active detectors providing reliable inputs for radiation model validation.

Interaction of (12)C ions with the mouse retinal response to light.

Astronauts in orbit reported phosphenes varying in shape and orientation across the visual field; incidence was correlated with the radiation flux. Patients with skull tumors treated by (12)C ions and volunteers whose posterior portion of the eye was exposed to highly ionizing particles in early studies reported comparable percepts. An origin in radiation activating the visual system is suggested. Bursts (∼ 4 ms) of (12)C ions evoked electrophysiological mass responses comparable to those to light in the retina of anesthetized wild-type mice at threshold flux intensities consistent with the incidence observed in humans. The retinal response amplitude increased in mice with ion intensity to a maximum at ∼ 2000 ions/burst, to decline at higher intensities; the inverted-U relationship suggests complex effects on retinal structures. Here, we show that bursts of (12)C ions presented simultaneously to white light stimuli reduced the presynaptic mass response to light in the mouse retina, while increasing the postsynaptic retinal and cortical responses amplitude and the phase-locking to stimulus of cortical low frequency and gamma (∼ 25-45 Hz) responses. These findings suggest (12)C ions to interfere with, rather than mimicking the light action on photoreceptors; a parallel action on other retinal structures/mechanisms resulting in cortical activation is conceivable. Electrophysiological visual testing appears applicable to monitor the radiation effects and in designing countermeasures to prevent functional visual impairment during operations in space.

Bovine rod rhodopsin: 2. Bleaching in vitro upon 12C ions irradiation as source of effects as light flash for patients and for humans in space.

PURPOSE: In a previous paper, we showed that chemiluminescence from radical recombination (initiated by lipid peroxidation and propagated by polyunsaturated fatty acids [PUFA]) has a bleaching effect comparable to that caused by light on the rhodopsin of retinal rod outer segment (RdOS) prepared from bovine eyes. Photons generated by radical recombination were suggested to be the origin of phosphenes perceived as light flashes by the human eye. Irradiation with (12)C carbon ions was used in this study to stimulate radical production, propagation and recombination leading to photoluminescence. MATERIALS AND METHODS: (12)C radiation bleached RdOS rhodopsin, but structural damage increasing with the radiation dose was also observed. For this reason, only the effects on rhodopsin at doses producing next to negligible biodamage and permitting regeneration have been considered as bleaching effects. RESULTS: (12)C irradiation bleached RdOS rhodopsin, but increasing structural damage with radiation dose was also observed. For the measure of bleaching and to reveal dose response effects on rhodopsin that were able to be regenerated only results from doses producing nearly negligible biodamage have been considered. CONCLUSIONS: Recombination of radicals appears responsible for the release of photons with subsequent bleaching of rhodopsin. This effect could have an important role in the generation of the anomalous visual effects (phosphenes) experienced by patients during hadrotherapy or by astronauts in space.

Electrophysiological monitoring in patients with tumors of the skull base treated by carbon-12 radiation therapy.

PURPOSE: To report the results of short-term electrophysiologic monitoring of patients undergoing (12)C therapy for the treatment of skull chordomas and chondrosarcomas unsuitable for radical surgery. METHODS AND MATERIALS: Conventional electroencephalogram (EEG) and retinal and cortical electrophysiologic responses to contrast stimuli were recorded from 30 patients undergoing carbon ion radiation therapy, within a few hours before the first treatment and after completion of therapy. Methodologies and procedures were compliant with the guidelines of the International Federation for Clinical Neurophysiology and International Society for Clinical Electrophysiology of Vision. RESULTS: At baseline, clinical signs were reported in 56.6% of subjects. Electrophysiologic test results were abnormal in 76.7% (EEG), 78.6% (cortical evoked potentials), and 92.8% (electroretinogram) of cases, without correlation with neurologic signs, tumor location, or therapy plan. Results on EEG, but not electroretinograms and cortical responses, were more often abnormal in patients with reported clinical signs. Abnormal EEG results and retinal/cortical responses improved after therapy in 40% (EEG), 62.5% (cortical potentials), and 70% (electroretinogram) of cases. Results on EEG worsened after therapy in one-third of patients whose recordings were normal at baseline. CONCLUSIONS: The percentages of subjects whose EEG results improved or worsened after therapy and the improvement of retinal/cortical responses in the majority of patients are indicative of a limited or negligible (and possibly transient) acute central nervous system toxicity of carbon ion therapy, with a significant beneficial effect on the visual pathways. Research on large samples would validate electrophysiologic procedures as a possible independent test for central nervous system toxicity and allow investigation of the correlation with clinical signs; repeated testing over time after therapy would demonstrate, and may help predict, possible late toxicity.

Electrophysiological responses of the mouse retina to 12C ions.

Phosphenes ("light flashes") have been reported by most astronauts on space missions and by healthy subjects whose eyes were exposed to ionizing radiation in early experiments in particle accelerators. The conditions of occurrence suggested retinal effects of heavy ions. To develop an in vivo animal model, we irradiated the eyes of anesthetized wild-type mice with repeated bursts of 12C ions delivered under controlled conditions in accelerator. 12C ions evoked electrophysiological retinal mass responses and activated the visual system as indicated by responses recorded from the visual cortex. No retinal immunohistological damage was detected. Mice proved a suitable animal model to study radiation-induced phosphenes in vivo and our findings are consistent with an origin of phosphenes in radiation activating the retina.

Nanocomposite polymeric electrolytes to record electrophysiological brain signals in prolonged, unconventional or extreme conditions.

Chemically stable nanocomposite iono-conducting polymeric membranes (based on lithium salts and nanocrystalline oxide powders dispersed in a polymethyl methacrylate matrix) performed successfully in the recording of human brain responses to visual stimulation. Impedance was higher than that of conventional electrodes. However, the electrophysiological signals recorded by acid Al(2)O(3) and neutral Al(2)O(3) 5 wt.% and 10 wt.% nanocomposite gel electrolytes were comparable to those obtained with standard electrodes, even without preliminary skin cleaning and in the absence of gel electrolytes allowing better contact with and skin-electrode ionic conductance. The electrochemical and mechanical characteristics of these membranes make them fit for human and animal research, for clinical application (specifically in emergencies, prolonged electrophysiological recordings), or in unconventional or extreme conditions when fluid electrolytes are unsuitable (e.g., biomedical space research).

Phosphenes in low earth orbit: survey responses from 59 astronauts.

INTRODUCTION: It has long been known that many people in space experience sudden phosphenes, or light flashes. Although it is clear that they are related to high-energy particles in the space radiation environment, many details about them are still unknown. In an effort to gain more knowledge about the light flashes, a study was initiated to collect information from people who have recently flown in space. METHOD: A survey conducted by anonymous questionnaire was performed among astronauts regarding their experience of sudden light flashes in space. In all, 98 surveys were distributed to current NASA and ESA astronauts. RESULTS: Among the 59 respondents, 47 noticed them sometime during spaceflight. Most often they were noted before sleep, and several people even thought the light flashes disturbed their sleep. The light flashes predominantly appear white, have elongated shapes, and most interestingly, often come with a sense of motion. The motion is described as sideways, diagonal, or in-out, but never in the vertical direction. DISCUSSION: Comparisons with earlier studies of light flashes in space and several ground-based studies during the 1970s are made. One interesting observation from this is that it seems that a small fraction of the light flashes is caused by Cherenkov radiation, while the majority is probably caused by some kind of direct interaction with elements in the retina.

Positive visual phenomena in space: A scientific case and a safety issue in space travel.

Most astronauts on Apollo, Skylab, and MIR reported 'flashes of light' occurring in different shapes and apparently moving across the visual field, in the absence of auditory, somatosensory, or olfactory abnormal percepts. A temporal correlation with heavy nuclei or protons has been documented in space and comparable phosphenes were observed by volunteers whose eyes were exposed to accelerated heavy ions at intensities below the threshold for Cerenkov visible radiation. An interaction between heavy ions and the retina was suggested. However, the biophysics of heavy ions or protons action remains undefined, the effects on photoreceptors and neuroretina have not been differentiated, and some direct action on the visual cortex never ruled out. Phosphenes are common in migraine and are known to occur also in response to the electrical stimulation of ganglion cells (in retinas without photoreceptors), optic pathways or visual cortex, with mechanisms that bypass the chemically gated channels. Intrinsic photosensitive ganglion cells exist in the retina of teleost fish and mammals. In the hypothesis of a peculiar sensitivity to subatomic particles of the visual system, phosphenes due to the activation of processes by-passing the photoreceptors would raise questions about human safety in space. The issue is particularly relevant with experiments of increasing duration being now operative in the International Space Station (ISS) and with plans of space travel outside the geomagnetic shield. Research is in progress both in the ISS and on animal models, in the framework of the NASA/ESA actions to improve the astronauts' health in space.