Charged Particle Irradiation Research Articles

Effects of ionizing radiation on the heart.

This article provides an overview of studies addressing effects of ionizing radiation on the heart. Clinical studies have identified early and late manifestations of radiation-induced heart disease, a side effect of radiation therapy to tumors in the chest when all or part of the heart is situated in the radiation field. Studies in preclinical animal models have contributed to our understanding of the mechanisms by which radiation may injure the heart. More recent observations in human subjects suggest that ionizing radiation may have cardiovascular effects at lower doses than was previously thought. This has led to examinations of low-dose photons and low-dose charged particle irradiation in animal models. Lastly, studies have started to identify non-invasive methods for detection of cardiac radiation injury and interventions that may prevent or mitigate these adverse effects. Altogether, this ongoing research should increase our knowledge of biological mechanisms of cardiovascular radiation injury, identify non-invasive biomarkers for early detection, and potential interventions that may prevent or mitigate these adverse effects.

Critical low-energy Ar-ion beam conditions to induce direct DNA double strand break

Abstract Ultra-low-energy ion interaction with naked DNA has been an interesting research topic as it can reveal fundamentals involved in charged particle irradiation effect on life as well as biological evolution. This study was a detailed investigation on ultra-low-energy argon ion bombardment effects on naked DNA. Argon ion beam was decelerated by a deceleration lens to ultra low energy ranging from about 1 keV down to a few tens of eV to bombard naked DNA plasmid pGFP to fluences of 1, 2 and 4 × 1015 ions/cm2. After ion bombardment, gel electrophoresis analyzed changes in the DNA topological form. The result showed that the DNA form changed, including from original supercoiled to damaged relaxed and linear forms, certainly depending on the ion energy and fluence. The DNA form changes as functions of the ion energy and fluence were quantified. It was found that the critical Ar-ion beam conditions were the energy 750 eV to be the lowest with the fluence 2 × 1015 ions/cm2 which could induce the linear DNA form, indicating direct double strand breaks, a more severe damage of DNA which might lead to mutation.

Monte Carlo simulation of radiation damage produced in iron and vanadium by primary knock on atom ‘PKA’

ABSTRACTAtomic scale simulation of radiation damage of pure iron and vanadium has been studied using the JA-IPU code based on Monte Carlo simulation. In response to gamma, neutron and any charged particle irradiation, energetic atoms knocked off their lattice position also generate atomic cascades inside the material besides the projectiles. The atomic cascade initiated by the primary knock on atoms (PKAs) of energy in the range 0–50 keV have been simulated in case of iron and vanadium metals. More realistic energy segregation has been achieved by incorporating electronic energy loss (EEL) along with nuclear stopping in the code. It is revealed that the effect of EEL is definite and different at low PKA energy as compared with high energy. The flip over energy is ∼8 keV in iron and ∼20 keV in the case of vanadium. This difference is found to be more in the case of the displacements than in the case of the defects. Cascade efficiency of vanadium calculated from the JA-IPU code has also been compared with the molecular dynamic simulation and found to be nearly the same.

Short DNA Fragments Are a Hallmark of Heavy Charged-Particle Irradiation and May Underlie Their Greater Therapeutic Efficacy.

Growing interest in proton and heavy ion therapy has reinvigorated research into the fundamental biological mechanisms underlying the therapeutic efficacy of charged-particle radiation. To improve our understanding of the greater biological effectiveness of high-LET radiations, we have investigated DNA double-strand breaks (DSBs) following exposure of plasmid DNA to low-LET Co-60 gamma photon and electron irradiation and to high-LET Beryllium and Argon ions with atomic force microscopy. The sizes of DNA fragments following radiation exposure were individually measured to construct fragment size distributions from which the DSB per DNA molecule and DSB spatial distributions were derived. We report that heavy charged particles induce a significantly larger proportion of short DNA fragments in irradiated DNA molecules, reflecting densely and clustered damage patterns of high-LET energy depositions. We attribute the enhanced short DNA fragmentation following high-LET radiations as an important determinant of the observed, enhanced biological effectiveness of high-LET irradiations.

SU‐F‐T‐127: Charged Particle Transport in Condensed Media

Purpose:Provide quality interaction cross sections for charged particle Monte Carlo (MC) track structure codes and evaluate low energy electron transport in condensed media.Methods:MC methods and codes are often used to model or simulate charged particle radiation transport in matter. Detailed (or event‐by‐event) track structure simulations are of special interest for the modeling of the physical and chemical stages of radiation action with matter and the initial radiation damage to biological systems. They require reliable interaction cross sections of all radiation qualities considered (e.g., electrons, protons, alpha particles, light and heavy ions) with the target material under consideration, mainly in the condensed phase, including liquids and solids. Interaction cross sections are calculated using the dielectric formalism, a mixture of first principles, theoretical modeling and experimental information for bulk and surface transport and implemented into MC track structure codes. Secondary electron emission yields from amorphous solid water (ASW) and thin metal foils (copper and gold) after fast proton impact are simulated and measured experimentally.Results:After considering different transport models for bulk and surface transport and a careful modeling of the experimental geometry, simulated secondary electron emission yields follow the trends of experimental data well. Furthermore, yields for electron emissions below 50 eV are sensitive to differential elastic scattering cross sections.Conclusion:Low‐energy electron transport in condensed media is still a challenge for detailed track structure simulation codes. Interaction cross‐sections, transport models, and target geometry need to be considered adequately.The research was funded in part by NSF Major Research Instrumentation Program 2009, Award Number: 0923270 and by NIH/NCI R01 CA93351.

Current Status and Future Prospects of Charged Particle Radiation Therapy

Current Status and Future Prospects of Charged Particle Radiation Therapy

Superresolution light microscopy shows nanostructure of carbon ion radiation-induced DNA double-strand break repair foci.

Carbon ion radiation is a promising new form of radiotherapy for cancer, but the central question about the biologic effects of charged particle radiation is yet incompletely understood. Key to this question is the understanding of the interaction of ions with DNA in the cell's nucleus. Induction and repair of DNA lesions including double-strand breaks (DSBs) are decisive for the cell. Several DSB repair markers have been used to investigate these processes microscopically, but the limited resolution of conventional microscopy is insufficient to provide structural insights. We have applied superresolution microscopy to overcome these limitations and analyze the fine structure of DSB repair foci. We found that the conventionally detected foci of the widely used DSB marker γH2AX (Ø 700-1000 nm) were composed of elongated subfoci with a size of ∼100 nm consisting of even smaller subfocus elements (Ø 40-60 nm). The structural organization of the subfoci suggests that they could represent the local chromatin structure of elementary DSB repair units at the DSB damage sites. Subfocus clusters may indicate induction of densely spaced DSBs, which are thought to be associated with the high biologic effectiveness of carbon ions. Superresolution microscopy might emerge as a powerful tool to improve our knowledge of interactions of ionizing radiation with cells.-Lopez Perez, R., Best, G., Nicolay, N. H., Greubel, C., Rossberger, S., Reindl, J., Dollinger, G., Weber, K.-J., Cremer, C., Huber, P. E. Superresolution light microscopy shows nanostructure of carbon ion radiation-induced DNA double-strand break repair foci.

Electromagnetic radiation of charged particles in stochastic motion

The study of the Brownian motion of a charged particle in electric and magnetic fields fields has many important applications in plasma and heavy ions physics, as well as in astrophysics. In the present paper we consider the electromagnetic radiation properties of a charged non-relativistic particle in the presence of electric and magnetic fields, of an exterior non-electromagnetic potential, and of a friction and stochastic force, respectively. We describe the motion of the charged particle by a Langevin and generalized Langevin type stochastic differential equation. We investigate in detail the cases of the Brownian motion with or without memory in a constant electric field, in the presence of an external harmonic potential, and of a constant magnetic field. In all cases the corresponding Langevin equations are solved numerically, and a full description of the spectrum of the emitted radiation and of the physical properties of the motion is obtained. The Power Spectral Density (PSD) of the emitted power is also obtained for each case, and, for all considered oscillating systems, it shows the presence of peaks, corresponding to certain intervals of the frequency.

A New Charging Model for Spacecraft Exposed Dielectric (SICCE)

The exposed dielectrics outside a spacecraft interact directly with the ambient plasma. Moreover, they are exposed to the energetic charged particle radiation. The low-energy plasma and the energetic radiation are both important factors for the dielectric charging. Tailored to this special condition, a model named surface and internal coupling charging model for exposed dielectric is newly proposed. It is based on the current conservation law regarding the charging potential as the unknown variable. All the three kinds of currents, namely the surface incident current, internal deposition current, and the leakage current, are considered. Among them, the leakage current is the most complicated, which is determined by the potential and the dielectric conductivity affected by the electric field, radiation dose rate, and temperature. The determinate solution of the model is analyzed and a numerical solution in 1-D case is provided using an iterative algorithm. The solution includes the potential of spacecraft body, distribution of dielectric potential, and electric field. If the internal deposition current is equal to zero, the new model degenerates into the one depicting the surface charging. A simulation is carried out to a polyimide dielectric board considering the typical environment of GEO orbit. The surface charging potential is verified by comparing with the online tool by ESA for surface charging. The internal charge deposition is found to have little effect on the surface charging potential, but it can result in electric field distortion, which is of significance for the dielectric breakdown discharge. Therefore, the new model can provide a more comprehensive assessment for the spacecraft exposed dielectric charging.

Differential Superiority of Heavy Charged-Particle Irradiation to X-Rays: Studies on Biological Effectiveness and Side Effect Mechanisms in Multicellular Tumor and Normal Tissue Models.

This review is focused on the radiobiology of carbon ions compared to X-rays using multicellular models of tumors and normal mucosa. The first part summarizes basic radiobiological effects, as observed in cancer cells. The second, more clinically oriented part of the review, deals with radiation-induced cell migration and mucositis. Multicellular spheroids from V79 hamster cells were irradiated with X-rays or carbon ions under ambient or restricted oxygen supply conditions. Reliable oxygen enhancement ratios could be derived to be 2.9, 2.8, and 1.4 for irradiation with photons, 12C+6 in the plateau region, and 12C+6 in the Bragg peak, respectively. Similarly, a relative biological effectiveness of 4.3 and 2.1 for ambient pO2 and hypoxia was obtained, respectively. The high effectiveness of carbon ions was reflected by an enhanced accumulation of cells in G2/M and a dose-dependent massive induction of apoptosis. These data clearly show that heavy charged particles are more efficient in sterilizing tumor cells than conventional irradiation even under hypoxic conditions. Clinically relevant doses (3 Gy) of X-rays induced an increase in migratory activity of U87 but not of LN229 or HCT116 tumor cells. Such an increase in cell motility following irradiation in situ could be the source of recurrence. In contrast, carbon ion treatment was associated with a dose-dependent decrease in migration with all cell lines and under all conditions investigated. The radiation-induced loss of cell motility was correlated, in most cases, with corresponding changes in β1 integrin expression. The photon-induced increase in cell migration was paralleled by an elevated phosphorylation status of the epidermal growth factor receptor and AKT-ERK1/2 pathway. Such a hyperphosphorylation did not occur during 12C+6 irradiation under all conditions registered. Comparing the gene toxicity of X-rays with that of particles using the γH2AX technique in organotypic cultures of the oral mucosa, the superior effectiveness of heavy ions was confirmed by a twofold higher number of foci per nucleus. However, proinflammatory signs were similar for both treatment modalities, e.g., the activation of NFκB and the release of IL6 and IL8. The presence of peripheral blood mononuclear cell increased the radiation-induced release of the proinflammatory cytokines by factors of 2–3. Carbon ions are part of the cosmic radiation. Long-term exposure to such particles during extended space flights, as planned by international space agencies, may thus impose a medical and safety risk on the astronauts by a potential induction of mucositis. In summary, particle irradiation is superior to gamma-rays due to a higher radiobiological effectiveness, a reduced hypoxia-induced radioresistance, a multicellular radiosensitization, and the absence of a radiation-induced cell motility. However, the potential of inducing mucositis is similar for both radiation types.

Influence of α particle radiation on the structural and electronic properties of thin film GaAs solar cells: A simulation study

Electronic and optoelectronic devices designed for high level of charged particle radiation environments, such as artificial satellites, spacecraft, stations of nuclear energy and nuclear arms, have special design challenges to prevent damage mechanisms in these devices. Ionizing radiation can lead to failure in semiconductor electronic devices. Due to the energy equipment from solar cells in mostly artificial satellites in space, these damages can degrade solar cell electrical properties and this could directly affect the durability and lifetime of the spacecraft in orbit. In this paper, a numerical simulation study on the influence of the high energy charged alpha (α) radiation on the performance of the nano-structured thin film GaAs solar cell has investigated. From the simulation analysis, it was found that α radiation ionizes the deep levels of the cell and most part of the total ion distribution (including different atoms in cell layers) was in the range of 1MeV α particles stopping range. This information is fundamentally important in interpreting and understanding the nature of bonding in the semiconductor solid state materials under irradiation. Hence these parameters are needed in determining design criteria in order to avoid in-service failure of electronic components. The radiation hardness is parameters which are required to fully describe the electronic property of the semiconductor electronic device. Simulation results show that major part of the cell damage occurred in the metal back contact with 100nm thickness. All simulation were done by SRIM 2013 software package.

The effects of the big storm events in the first half of 2015 on the radiation belts observed by EPT/PROBA-V

Abstract. With the energetic particle telescope (EPT) performing with direct electron and proton discrimination on board the ESA satellite PROBA-V, we analyze the high-resolution measurements of the charged particle radiation environment at an altitude of 820 km for the year 2015. On 17 March 2015, a big geomagnetic storm event injected unusual fluxes up to low radial distances in the radiation belts. EPT electron measurements show a deep dropout at L > 4 starting during the main phase of the storm, associated to the penetration of high energy fluxes at L < 2 completely filling the slot region. After 10 days, the formation of a new slot around L = 2.8 for electrons of 500–600 keV separates the outer belt from the belt extending at other longitudes than the South Atlantic Anomaly. Two other major events appeared in January and June 2015, again with injections of electrons in the inner belt, contrary to what was observed in 2013 and 2014. These observations open many perspectives to better understand the source and loss mechanisms, and particularly concerning the formation of three belts.

S-phase-specific radiosensitization by gemcitabine for therapeutic carbon ion exposure in vitro.

Densely ionizing charged particle irradiation offers physical as well as biological advantages compared with photon irradiation. Radiobiological data for the combination of such particle irradiation (i.e. therapeutic carbon ions) with commonly used chemotherapeutics are still limited. Recent in vitro results indicate a general prevalence of additive cytotoxic effects in combined treatments, but an extension of established multimodal treatment regimens with photons to the inclusion of particle therapy needs to evaluate possible peculiarities of using high linear energy transfer (LET) radiation. The present study investigates the effect of combined radiochemotherapy using gemcitabine and high-LET irradiation with therapeutic carbon ions. In particular, the earlier observation of S-phase specific radiosensitization with photon irradiation should be evaluated with carbon ions. In the absence of the drug gemcitabine, carbon ion irradiation produced the typical survival behavior seen with X-rays—increased relative biological efficiency, and depletion of the survival curve's shoulder. By means of serum deprivation and subsequent replenishment, ∼70% S-phase content of the cell population was achieved, and such preparations showed radioresistance in both treatment arms—,photon and carbon ion irradiation. Combined modality treatment with gemcitabine caused significant reduction of clonogenic survival especially for the S-phase cells. WIDR cells exhibited S-phase–specific radioresistance with high-LET irradiation, although this was less pronounced than for X-ray exposure. The combined treatment with therapeutic carbon ions and gemcitabine caused the resistance phenomenon to disappear phenotypically.

Melatonin and charged particle irradiation inhibit tumor angiogenesis

Melatonin and charged particle irradiation inhibit tumor angiogenesis

Efficacy and Safety of Adjuvant Proton Therapy Combined With Surgery for Chondrosarcoma of the Skull Base: A Retrospective, Population-Based Study

Chondrosarcoma is a rare malignant tumor of the cartilage affecting young adults. Surgery, followed by charged-particle irradiation, is considered the reference standard for the treatment of patients with grade I to II skull base chondrosarcoma. The present study was conducted to assess the effect of the quality of surgery and radiation therapy parameters on local control (LC) and overall survival (OS). From 1996 to 2013, 159 patients (median age 40 years, range 12-83) were treated with either protons alone or a combination of protons and photons. The median total dose delivered was 70.2 Gy (relative biologic effectiveness [RBE]; range 67-71). Debulking and biopsy were performed in 133 and 13 patients, respectively. With a median follow-up of 77 months (range 2-214), 5 tumors relapsed based on the initial gross tumor volume. The 5- and 10-year LC rates were 96.4% and 93.5%, respectively, and the 5- and 10-year OS rates were 94.9% and 87%, respectively. A total of 16 patients died (13 of intercurrent disease, 3 of disease progression). On multivariate analysis, age <40 years and primary disease status were independent favorable prognostic factors for progression-free survival and OS, and local tumor control was an independent favorable predictor of OS. In contrast, the extent of surgery, dosimetric parameters, and adjacent organs at risk were not prognostic factors for LC or OS. Systematic high-dose postoperative proton therapy for skull base chondrosarcoma can achieve a high LC rate with a low toxicity profile. Maximal safe surgery, followed by high-dose conformal proton therapy, is therefore recommended.

Spectral and angular radiation characteristics of a charged particle in the plane monochromatic electromagnetic wave

Relying upon the solution of the relativistic equation of charged-particle motion that was obtained by Rukhadze et al., the spectral and angular characteristics of ultra-relativistic intensive radiation of a relativistic charged particle have been studied, the particle being linearly accelerated by a superpower laser pulse. The case where the particle propagates in vacuum without brake light was examined. The interaction of the charged particle with the large-amplitude ultra-short laser pulse was analyzed in details using the relativistic consideration. Formulae for the average radiated power of the relativistic charged particle, depending on the initial conditions, the electromagnetic-wave amplitude, intensity and polarization were obtained. For the case where the laser pulse can be represented by a monochromatic plane wave, analytical expressions for the radiation characteristics were put forward and the phase-angular distributions of relativistic radiated power and intensity were found. The Fourier transform of the electric-intensity radiation field of the charged particle and the particle's spectral density radiation in the field of a plane monochromatic wave for different types of polarization (linear and circular ones) were determined.

On the electrodynamics of continuous media

Radiation of fast charged particles in the presence of the interface between hollow space and “left-handed” ferrodielectric is considered. The quantitative identity of various phenomena in the case of “different-right-handed” media is revealed. It is shown that transition radiation at the interface with a “left-handed” medium is quantitatively identical to the case of annihilation radiation at the interface with a “right-handed” medium with participation of various charged particles. Transition radiation of the charged particle at the interface with a uniaxial crystal is generalized to radiation with participation of particles with various charges and velocities.

The study of the carriers’ transport mechanism of GaAs/Ge solar cells based on irradiation damage model

Based on the irradiation damage model of solar cells, the irradiation damage mechanism of space solar cells from the aspect of the carriers’ transport is studied. The basic rules of electrical parameter degradation of GaAs/Ge solar cells under different energy proton and electron irradiation are obtained through the ground-accelerated equivalent simulation test for space-charged particles. The open-circuit voltage degradation curves of the solar cells are fitted nonlinearly by its mathematical model. The change laws of damage coefficient of majority carriers’ removal rate with the incident proton and electron energy are given. The damage coefficient of GaAs/Ge solar cells first increases and then decreases with increasing incident proton energy, and it reaches a maximum at 100keV proton irradiation. In addition, the damage coefficient increases with increasing incident electron energy. The studies show that open-circuit voltage degradation is closely related to the removal effect of the majority carriers under charged particle irradiation. The results have important significance to reveal the irradiation damage mechanism of the space solar cells.

Irradiation of Neurons with High-Energy Charged Particles: An In Silico Modeling Approach.

In this work, a stochastic computational model of microscopic energy deposition events is used to study for the first time damage to irradiated neuronal cells of the mouse hippocampus. An extensive library of radiation tracks for different particle types is created to score energy deposition in small voxels and volume segments describing a neuron’s morphology that later are sampled for given particle fluence or dose. Methods included the construction of in silico mouse hippocampal granule cells from neuromorpho.org with spine and filopodia segments stochastically distributed along the dendritic branches. The model is tested with high-energy 56Fe, 12C, and 1H particles and electrons. Results indicate that the tree-like structure of the neuronal morphology and the microscopic dose deposition of distinct particles may lead to different outcomes when cellular injury is assessed, leading to differences in structural damage for the same absorbed dose. The significance of the microscopic dose in neuron components is to introduce specific local and global modes of cellular injury that likely contribute to spine, filopodia, and dendrite pruning, impacting cognition and possibly the collapse of the neuron. Results show that the heterogeneity of heavy particle tracks at low doses, compared to the more uniform dose distribution of electrons, juxtaposed with neuron morphology make it necessary to model the spatial dose painting for specific neuronal components. Going forward, this work can directly support the development of biophysical models of the modifications of spine and dendritic morphology observed after low dose charged particle irradiation by providing accurate descriptions of the underlying physical insults to complex neuron structures at the nano-meter scale.

A Single Low Dose of Proton Radiation Induces Long-Term Behavioral and Electrophysiological Changes in Mice.

Astronauts traveling outside Earth's magnetosphere risk exposure to charged particle radiation that may cause neurophysiological changes and behavioral deficits. Although proton particles comprise a large portion of the space radiation environment, little has been published on the effects of low-dose proton radiation on central nervous system function. In the current study, we irradiated young male mice with 0.5 Gy 150 MeV protons and assessed the effects on behavior and hippocampal neurophysiology. Spatial learning ability, a sensitive behavioral marker of hippocampal damage, was assessed using the water maze and Barnes maze before irradiation and repeatedly 3 and 6 months after irradiation. Evoked field excitatory postsynaptic potentials (fEPSPs) and population spikes, long-term potentiation (LTP) and spontaneous oscillations (SOs) triggered by incubation with Mg(2+)-free media (reflecting interictal epileptiform activity) were assessed 9 months after irradiation in vitro in hippocampal slice preparations. Irradiated mice exhibited impaired reversal learning in the water maze compared to control mice 6 months after irradiation. Proton radiation did not affect LTP, but significantly increased fEPSP slopes and reduced the incidence of SOs 9 months after irradiation. These findings suggest that a single exposure to low-dose proton radiation can increase synaptic excitability and suppress the propensity for epileptiform activity. Such findings of functional alterations in the irradiated mouse hippocampus have implications for extended manned space missions planned in the near future.