Accelerated Carbon Ions Research Articles

Towards ion stopping power experiments with the laser-driven LIGHT beamline

The main emphasis of the Laser Ion Generation, Handling and Transport (LIGHT) beamline at GSI Helmholtzzentrum für Schwerionenforschung GmbH are phase-space manipulations of laser-generated ion beams. In recent years, the LIGHT collaboration has successfully generated and focused intense proton bunches with an energy of 8 MeV and a temporal duration shorter than 1 ns (FWHM). An interesting area of application that exploits the short ion bunch properties of LIGHT is the study of ion-stopping power in plasmas, a key process in inertial confinement fusion for understanding energy deposition in dense plasmas. The most challenging regime is found when the projectile velocity closely approaches the thermal plasma electron velocity ( $v_{i}\approx v_{e,\text {th}}$ ), for which existing theories show high discrepancies. Since conclusive experimental data are scarce in this regime, we plan to conduct experiments on laser-generated plasma probed with ions generated with LIGHT at a higher temporal resolution than previously achievable. The high temporal resolution is important because the parameters of laser-generated plasmas are changing on the nanosecond time scale. To meet this goal, our recent studies have dealt with ions of lower kinetic energies. In 2021, laser accelerated carbon ions were transported with two solenoids and focused temporally with LIGHT's radio frequency cavity. A bunch length of 1.2 ns (FWHM) at an energy of 0.6 MeV u $^{-1}$ was achieved. In 2022, protons with an energy of 0.6 MeV were transported and temporally compressed to a bunch length of 0.8 ns. The proton beam was used to measure the energy loss in a cold foil. Both the ion and proton beams will also be employed for energy loss measurements in a plasma target.

Future Perspective: Carbon Ion Radiotherapy for Head and Neck and Skull Base Malignancies.

Head and neck and base of skull malignancies are challenging for surgical and radiotherapy treatment due to the density of sensitive tissues. Carbon ion radiotherapy (CIRT) is a form of heavy particle therapy that uses accelerated carbon ions to treat malignancies that may be radioresistant or in challenging anatomic locations. CIRT has an increased biological effectiveness (ie, increased cell killing) at the end of the range of the carbon beam (ie, within the target tissue) but not in the entrance dose. This increased biological effectiveness can overcome the effects of radioresistant tumors, tissue hypoxia, and the need for radiotherapy fractionation.

Comparison of the dynamics of DNA damage in blood leukocytes and survival of mice after total body irradiation with Bragg peak carbon ions or x-rays

This study has determined a survival rate of mice irradiated with accelerated carbon ions (450 MeV/nucleon) in the Bragg peak or X-ray at a dose of 6.5 Gy, using the comet assay. Levels of DNA damage (%TDNA) in blood leukocytes from mice were measured 1 day before, 1-23 days after exposure to carbon ions and 1-28 days after exposure to X-ray radiation at the same dose. According to survival and % TDNA parameters, it was found that a damaging effect of carbon ions is greater than that of X-rays and substantial variations in % TDNA, which occur in individual animals, could appear to cause individual differences in the development of genome instability in the long term. It is assumed that a higher % TDNA in leukocytes after carbon ion exposure compared to that of X-rays, a wide range of variations and asynchronous changes in individuals in the post-irradiation period are associated with the induction of clustered DNA damages and mitochondrial dysfunction, and are also due to genetic and epigenetic factors. The results obtained point to the need to assess the state of blood leukocytes in animals with a heterogeneous genetic background using the comet assay before irradiation in order to form a group with similar %TDNA values. The revealed differences in individual laboratory animals require further study in order to improve animal models in the light of the development of personalized biomedicine.

Активность сукцинат- и лактатдегидрогеназы лимфоцитов, индуцированные АФК нейтрофилов и повреждение ДНК лейкоцитов в крови облучённых ионами углерода мышей

At the present time, the studies carried out to improve the radiotherapy of tumors using accelerated heavy ions are of great interest, since they give off the main energy at the end of the run at the Bragg peak, which increases the severity of radiation damage to the tumor and minimizes damage to surrounding healthy tissues. In this work, the levels of lymphocyte lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) activity, the ratio of LDH/SDH, induced reactive oxygen species (ROS) of neutrophils, and leukocytes DNA damage (%TDNA) in blood 1 day after accelerated carbon ions irradiation of mice with an energy of 450 MeV/nucleon in doses of 0.2-2 Gy in the Bragg peak were determined. Found: SDH activity increased at doses of 0.2-1 Gy and sharply decreased at a dose of 1.5 Gy in all mice. With a decrease in SDH activity, glycolysis (LDH activity) increased compensatory, which, apparently, is associated with the developing mitochondrial dysfunction of immune cells. The %TDNA of leukocytes increased depending on the dose and was accompanied by a decrease in the functional activity of neutrophils - the zymosan-induced ROS production decreased. Thus, against the background of an increased %TDNA and a decrease in SDH activity, glycolysis becomes of great importance. The applied methods are highly sensitive and can be used to detect individual differences in animals that are biological models in preclinical studies.

The Combined Effect of Protective Agents and Accelerated Carbon Ions on the Behavior of Mice

The Combined Effect of Protective Agents and Accelerated Carbon Ions on the Behavior of Mice

Synthetic torpor protects rats from exposure to accelerated heavy ions

Hibernation or torpor is considered a possible tool to protect astronauts from the deleterious effects of space radiation that contains high-energy heavy ions. We induced synthetic torpor in rats by injecting adenosine 5′-monophosphate monohydrate (5′-AMP) i.p. and maintaining in low ambient temperature room (+ 16 °C) for 6 h immediately after total body irradiation (TBI) with accelerated carbon ions (C-ions). The 5′-AMP treatment in combination with low ambient temperature reduced skin temperature and increased survival following 8 Gy C-ion irradiation compared to saline-injected animals. Analysis of the histology of the brain, liver and lungs showed that 5′-AMP treatment following 2 Gy TBI reduced activated microglia, Iba1 positive cells in the brain, apoptotic cells in the liver, and damage to the lungs, suggesting that synthetic torpor spares tissues from energetic ion radiation. The application of 5′-AMP in combination with either hypoxia or low temperature environment for six hours following irradiation of rat retinal pigment epithelial cells delays DNA repair and suppresses the radiation-induced mitotic catastrophe compared to control cells. We conclude that synthetic torpor protects animals from cosmic ray-simulated radiation and the mechanism involves both hypothermia and hypoxia.

Induced radiation studies and personnel dose assessment in a carbon ion therapy facility

Carbon ions have become the most widely used particles in heavy-ion tumor therapy due to favorable physical and biological characteristics. The beam delivery system (BDS) and tumor tissues are directly bombarded with accelerated carbon ions, resulting in activation products in the components and the patient’s body. The results of an experimental study and a Monte-Carlo simulation for the radioactivity induced in a treatment room under a uniform scanning mode were presented in this study. They indicated that the multi-leaf collimator (MLC) and the patient’s body were the main sources of induced radioactivity. The half-lives of the main produced radionuclides ranged from a few minutes to tens of minutes for single irradiation and from dozens of days to hundreds of days for long-term irradiation. The personal dose of medical staff working in the treatment room and the additional dose of the patient from the induced radioactivity were estimated. Finally, some suggestions were made to reduce the unwanted radiation exposure of the medical staff, patients, and carers.

Single-Shot Diagnostics of Beam Particle Number for Laser Accelerated Carbon Ion

Single-Shot Diagnostics of Beam Particle Number for Laser Accelerated Carbon Ion

Low dose of carbon ion irradiation induces early delayed cognitive impairments in mice.

People often encounter various sources of ionizing radiation, both in modern medicine and under various environmental conditions, such as space travel, nuclear power plants or in conditions of man-made disasters that may lead to long-term cognitive impairment. Whilst the effect of exposure to low and high doses of gamma and X-radiation on the central nervous system (CNS) has been well investigated, the consequences of protons and heavy ions irradiation are quite different and poorly understood. As for the assessment of long-term effects of carbon ions on cognitive abilities and neurodegeneration, very few data appeared in the literature. The main object of the research is to investigate the effects of accelerated carbon ions on the cognitive function. Experiments were performed on male SHK mice at an age of two months. Mice were irradiated with a dose of 0.7Gy of accelerated carbon ions with an energy of 450meV/n in spread-out Bragg peak (SOBP) on a U-70 particle accelerator (Protvino, Russia). Two months after the irradiation, mice were tested for total activity, spatial learning, as well as long- and short-term hippocampus-dependent memory. One month after the evaluation of cognitive activity, histological analysis of dorsal hippocampus was carried out to assess its morphological state and to reveal late neuronal degeneration. It was found that the mice irradiated with accelerated carbon ions develop an altered behavioral pattern characterized by anxiety and a shortage in hippocampal-dependent memory retention, but not in episodic memory. Nissl staining revealed a reduction in the number of cells in the dorsal hippocampus of irradiated mice, with the most pronounced reduction in cell density observed in the dentate gyrus (DG) hilus. Also, the length of the CA3 field of the dorsal hippocampus was significantly reduced, and the number of cells in it was moderately decreased. Experiments with the use of Fluoro-Jade B (FJB) staining revealed no FJB-positive regions in the dorsal hippocampus of irradiated and control animals 3 months after the irradiation. Thus, no morbid cells were detected in irradiated and control groups. The results obtained indicate that total irradiation with a low dose of carbon ions can produce a cognitive deficit in adult mice without evidence of neurodegenerative pathologic changes.

Эффекты гиперчувствительности и индуцированной радиорезистентности в клетках СНО-К1 после воздействия гамма-излучения и ускоренных ионов углерода

The study presents results of investigations on chromosome aberrations (CA) yield in Chinese ham-ster ovary cells after exposure to gamma-rays and accelerated carbon ions (455 MeV/amu) at doses less than 1 Gy in the pristine Bragg curve plateau and behind the Bragg peak, where normal tissues are situated in the course of radiotherapy. Initial parts of dose curves for total CA and terminal deletions frequencies differed from linear-quadratic dependence and the region of induced radioresistance were observed at 0.1-0.6 Gy for gamma-rays. The similar curve shapes were detected for carbon ions, but plateau region was shorter (0.15-0.35 Gy). Despite the uniform shape of the dose curves for the CA yield, a definite dependence of the cytogenetic effect on the linear energy transfer (LET) is observed. The CA frequency increased with LET rising in the order: gamma-irradiation (0.2 keV/μm), carbon ions at the Bragg curve plateau (10-12 keV/μm) and at the «tail» of Bragg peak (25-27 keV/μm). Outside this range, the yield of chromosome aberrations also enhanced with increasing LET in the same order. The results obtained confirm that the hypersensitivity and induced radioresistance phenomena are characteristic for low level exposure to low-LET and middle-LET radiations when chromosome aberration test is used.

The Early Delayed Effect of Accelerated Carbon Ions and Protons on the Cognitive Functions of Mice

The early delayed effects of accelerated carbon ions and protons on the cognitive functions of mice using tests of the total activity, spatial learning, and long-term and short-term hippocampal-dependent memory were studied. The obtained results showed that irradiated animals do not develop an altered behavioral pattern: the level of anxiety is not increased, the exploratory model of behavior is clearly pronounced, and there is no deficiency of hippocampal-dependent memory. However, the long-term memory test revealed fewer errors in finding an escape box in a group of animals irradiated with protons compared to the control animals and mice irradiated with carbon ions. The results may indicate a better preservation of memory traces under these conditions.

DNA damage in blood leukocytes from mice irradiated with accelerated carbon ions with an energy of 450 MeV/nucleon

Purpose The objective of the study was to estimate the DNA damage in blood leukocytes at long terms after irradiation of mice with carbon ions (450 MeV/nucleon) both before and in the Bragg peak. Materials and methods White outbred SHK male mice were exposed to whole-body irradiation with carbon ions at doses of 0.1–2 Gy in the spread-out Bragg peak and at a dose of 6 Gy before and in the Bragg peak. At different times after irradiation (1–75 days), whole blood was collected from the tail of each mouse and analyzed by the comet assay. Mice X-irradiated in the same dose range served as a positive control. The level of the expression of mRNA of CDKN1A, APEX1, BBC3, TXN2, and β-ACT genes in bone marrow cells was determined in animals irradiated with carbon ions at doses of 0.1–2 Gy using the real-time PCR. Results It was found that, 24 h after 12C-irradiation, a dose-dependent (0.1–2 Gy) increase in the DNA damage of leukocytes occurred, which was accompanied by a decrease in their concentration and an increase in the expression of the CDKN1A and BBC3 genes in bone marrow cells. The expression of the APEX1 and TXN2 genes did not change. In mice 12C-irradiated at a dose of 6 Gy before and in the Bragg peak, the level of DNA damage changed as follows: by day 3, it increased; by day 23 it returned to the control level; by day 30, it increased again; and by day 75, it fell to the control level on irradiation before the Bragg peak and was significantly higher (p < .05) than in the control after irradiation in the Bragg peak. Conclusions The dynamics of changes in the level of DNA damage in leucocytes of 12C-irradiated mice within 30 days is similar to that in mice exposed to sublethal doses of X-radiation. The retention of the high level of DNA damage by day 75 after 12C-irradiation in the Bragg peak indicates a significant injury of cells from different cell pools of the blood system. The high level of DNA damage may be related not only to complex DNA injuries but also to chronic oxidative stress.

Assessment of the Biological Efficiency of 450 MeV/Nucleon Accelerated Carbon Ions in the U-70 Accelerator According to the Criterion of Mouse Survival

Abstract—The coefficients of the relative biological efficiency of a carbon ion beam with an energy of 450 MeV/nucleon upon the irradiation of mice at a dose of 6.5 Gy in different parts of the Bragg curve have been determined by the 30-day survival test, the dynamics of death, and the average life expectancy of mice in comparison with exposure to X-ray radiation. The integral value ​​of the coefficients of the relative biological efficiency of carbon ions upon irradiation before the Bragg peak is 0.8, in the spread-out Bragg peak it is 1.5, and after the Bragg peak, it is 0.7. The value of the relative biological efficiency in the modified Bragg peak, as calculated by the ratio of doses that lead to the death of 50% of the animals, was 2.9. Changes of the width of the modified Bragg peak did not affect the death rate of the animals.

Investigation of accelerated carbon ions with the presence of QED effect by ultra-intense high-power lasers

In this study, we have investigated carbon ions, fast electrons and gamma-ray energy spectra and the corresponding temperatures when next-generation 10 petawatt (PW) lasers (irradiances of $$5\times 10^{22} \, {\mathrm {W}}\, {\mathrm {cm}}^{-2}$$ ) hit solid targets with a preformed plasma at the front surface. We employed 2D particle-in-cell (PIC) code with the presence of quantum electrodynamics (QED) effects. The maximum energy reached by the accelerated particles, and the corresponding temperature due to nonlinear plasma processes can be affected by varied plasma scale lengths. Here, we show the effects of varied plasma scale lengths on particle acceleration at irradiances on the order of $$10^{22}\,{\mathrm {W}}\,{\mathrm {cm}}^{-2}$$ , which is a new development for laser technology. We have observed that fully ionized carbon ions can reach up to 2.5 GeV energies with an optimum plasma scale length of $$1\, \upmu \hbox {m}$$ and the corresponding temperature of 40 MeV. Accelerated electron energies reach up to 1.5 GeV with the temperatures of 50 MeV for 10 PW laser–plasma interactions with the presence of QED effects. We have demonstrated that by varying plasma scale length, heavy ion energy and temperature can be controlled, which is important for various applications such as hadron therapy and X-ray imaging.

Сравнение биологической эффективности ускоренных ионов углерода и тяжёлых ядер отдачи на клетках китайского хомячка

Сравнение биологической эффективности ускоренных ионов углерода и тяжёлых ядер отдачи на клетках китайского хомячка

Charge-Transfer Processes in Warm Dense Matter: Selective Spectral Filtering for Laser-Accelerated Ion Beams.

We investigate, both experimentally and theoretically, how the spectral distribution of laser accelerated carbon ions can be filtered by charge exchange processes in a double foil target setup. Carbon ions at multiple charge states with an initially wide kinetic energy spectrum, from 0.1 to 18MeV, were detected with a remarkably narrow spectral bandwidth after they had passed through an ultrathin and partially ionized foil. With our theoretical calculations, we demonstrate that this process is a consequence of the evolution of the carbon ion charge states in the second foil. We calculated the resulting spectral distribution separately for each ion species by solving the rate equations for electron loss and capture processes within a collisional radiative model. We determine how the efficiency of charge transfer processes can be manipulated by controlling the ionization degree of the transfer matter.

Influence of Manufacturing Accuracy on Magnetic Field Distribution in Magnet for HTS Rotating Gantry

Because of its high curative effects and low burden on patients, carbon ion cancer therapy is becoming more widely used. The accelerated carbon ions are delivered to patients via electromagnets on a rotating gantry. One advantage of a rotating gantry is that a tumor can be irradiated with carbon ions from any direction without changing the posture of the patient. On the other hand, because of the high magnetic rigidity of carbon ions, rotating gantries for carbon cancer therapy are about three times heavier than those for proton cancer therapy, according to our estimation. Use of high-temperature superconducting (HTS) magnets has been considered for reducing the size of the rotating gantry for carbon cancer therapy. For accurate irradiation, these HTS magnets must generate high-uniformity magnetic fields, and the shape of the HTS coils was designed by 3-D analysis to generate uniform magnetic fields. In our design, saddle-shaped HTS coils were used since they can efficiently generate a magnetic field. The conductor positions and the coil end shape were optimized to generate a uniform magnetic field. On the other hand, it was difficult to maintain the HTS conductor in the designed saddle shape because it has a tapelike shape and anisotropic flexibility in bending. In this paper, the winding accuracy of the fabricated HTS saddle-shaped coil was measured, and the influence of the measurement result on the magnetic field distribution was evaluated.

The dynamics of monoamine metabolism in rat brain structures in the late period after exposure to accelerated carbon ions

We studied the effect of carbon ions (12C) with an energy of 500 MeV/nucleon at a dose of 1 Gy on monoamine metabolism in the brains of rats of different ages. Neurochemical parameters that characterize the distribution of noradrenaline (NA), dopamine (DA), serotonin (5-HT), and its metabolites were evaluated during 2 months on days 30 and 90 after the exposure to radiation. We studied the prefrontal cortex, hypothalamus, hippocampus, and striatum. The results showed changes in the activities of the NA, DA, and 5-HT systems in rats of different age groups after exposure to radiation. The most prominent differences in the exposed and control animals were observed in the prefrontal cortex and hypothalamus, which indicates the important role of these brain regions in long-term effects of exposure to radiation on the central nervous system. A comparison of animals from different age groups showed a decrease in the intensity of the temporal changes in all analyzed structures except the striatum in the exposed rats. Based on these findings, we assumed that the activation of compensatory and repairing mechanisms occurs in the late post-radiation period. At relatively low linear energy transfer of particles (10.6 keV/µm), it may lead to the partial recovery of brain functions that were impaired by radiation. At higher values of the linear energy transfer, the compensatory and recovery processes are activated to a lesser degree and functional impairment increases with time.

Evaluation of an empirical monitor output estimation in carbon ion radiotherapy

A conventional broad beam method is applied to carbon ion radiotherapy at Gunma University Heavy Ion Medical Center. According to this method, accelerated carbon ions are scattered by various beam line devices to form 3D dose distribution. The physical dose per monitor unit (d/MU) at the isocenter, therefore, depends on beam line parameters and should be calibrated by a measurement in clinical practice. This study aims to develop a calculation algorithm for d/MU using beam line parameters. Two major factors, the range shifter dependence and the field aperture effect, are measured via PinPoint chamber in a water phantom, which is an identical setup as that used for monitor calibration in clinical practice. An empirical monitor calibration method based on measurement results is developed using a simple algorithm utilizing a linear function and a double Gaussian pencil beam distribution to express the range shifter dependence and the field aperture effect. The range shifter dependence and the field aperture effect are evaluated to have errors of 0.2% and 0.5%, respectively. The proposed method has successfully estimated d/MU with a difference of less than 1% with respect to the measurement results. Taking the measurement deviation of about 0.3% into account, this result is sufficiently accurate for clinical applications. An empirical procedure to estimate d/MU with a simple algorithm is established in this research. This procedure allows them to use the beam time for more treatments, quality assurances, and other research endeavors.

Effect of High Intensity Pulsed Ion Beam of Carbon on Subsurface Layers of Zirconia Ceramics

The effect of high intensity pulsed beam (HIPB) of accelerated carbon ions on zirconia ceramics of the 97ZrO2-3Y2O3 (in mol %) composition is investigated. The parameters of the ion beam are as follows: the energy of the accelerated ions is 200 keV, pulse duration is 100 ns, pulse current density equal to 40 and 150 A/cm2. It was revealed that ions treatment of ceramics leads to melting of the subsurface layer. In this area, the grains are elongated towards the surface. Upon treatment of ceramics by accelerated ions with the pulse energy density equal to 3 J/cm2 (fluence ≥ 9.4•1015 cm–2), formation of zirconia cubic phases up to 30 mass % is observed. The size of coherent-scattering region X-rays of the grains of the c-ZrO2 phase is 15–20 nm. The analysis of the elemental composition of the irradiated surface layers by secondary ion mass spectrometry (SIMS) method makes possible to conclude that formation of high concentration of non-stoichiometric oxygen vacancies under ion treatment is the main cause of the cubic phase stabilization in zirconia.