Heavy Ion Medical Accelerator Research Articles

Performance of the prototype beam drift chamber for LAMPS at RAON with proton and 12C beams

Beam Drift Chamber (BDC) is designed to reconstruct the trajectories of incident rare isotope beams provided by RAON (Rare isotope Accelerator complex for ON-line experiments) into the experimental target of LAMPS (Large Acceptance Multi-Purpose Spectrometer). To conduct the performance test of the BDC, the prototype BDC (pBDC) is manufactured and evaluated with the high energy ion beams from HIMAC (Heavy Ion Medical Accelerator in Chiba) facility in Japan. Two kinds of ion beams, 100 MeV proton, and 200 MeV/u 12C, have been utilized for this evaluation, and the track reconstruction efficiency and position resolution have been measured as the function of applied high voltage. This paper introduces the construction details and presents the track reconstruction efficiency and position resolution of pBDC.

3D track extraction from a fluorescent nuclear track detector via machine learning and an application to diagnostics of laser-driven ions.

We have developed an ion diagnostic method for laser-driven ion acceleration experiments that uses fluorescent nuclear track detectors (FNTDs). An FNTD records the particle tracks as color centers and does not require chemical etching, unlike CR-39 track detectors. The color centers are observed using a confocal laser microscope, and 3D particle tracks can be obtained by changing its focal position. The intensity of the color centers corresponds to the energy deposited by the ions. The nuclides of the ions can be determined from the intensity distribution of the color centers as a function of depth and the distance between the stopping point and the surface of the detector. To extract the intensity distribution, we must track the same ion tracks in the depth-layered microscopic images from the surface to the stopping point, even if they overlap with those of other ions. In addition, since an FNTD is sensitive not only to ions but also to electrons and photons, we must identify ion tracks among those from the latter particles. To analyze a statistical number of ion tracks, it is necessary to automate these processes. We have thus developed a method for automated ion detection and 3D tracking that relies on a support vector classifier and a kernelized correlation filter. This method was tested on a laser ion acceleration experiment performed using the J-KAREN-P laser. The method automatically detects ion tracks on FNTDs and tracks them in the depth direction. The training data are sampled from the Heavy-Ion Medical Accelerator in Chiba.

Space radiation research with heavy ions at HIMAC

The HIMAC (Heavy Ion Medical Accelerator in Chiba) was originally designed principally for carbon ion therapy, but heavy ion research projects in medicine, physics, chemistry and biology have been conducted under a collaborative research framework since 1994. One major application is space radiation research. The radiation in space of greatest interest for human space exploration consists of energetic protons and heavy ions which can affect the health of space crew and lead to the failure of electronic devices. Ground-based experiments at heavy ion accelerators are crucial for ensuring mission crew safety and for understanding the biological effects of long-term exposure to space radiation. HIMAC provides a range of linear energy transfer (LET) beams from protons to Xe ions at energies up to 800 MeV/u, representing the most biologically-significant components of the space radiation field. At HIMAC a variety of radiation detectors and instruments are characterized and calibrated for dosimetry using specific mono-energetic heavy ion beams, the performance of shielding materials for mitigating space radiation dose is evaluated, radiation hardness of electronic devices is tested to ensure their safe operation in space, and the radiobiological studies are conducted to understand biological effects in humans during long-term space activities. HIMAC is an indispensable simulator of space radiation for the new decade of space exploration.

First experimental demonstration of real-time neutron capture discrimination in helium and carbon ion therapy

This work provides the first experimental proof of an increased neutron capture photon signal following the introduction of boron to a PMMA phantom during helium and carbon ion therapies in Neutron Capture Enhanced Particle Therapy (NCEPT). NCEPT leverages 10\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{10}$$\\end{document}B neutron capture, leading to the emission of detectable 478 keV photons. Experiments were performed at the Heavy Ion Medical Accelerator in Chiba, Japan, with two Poly(methyl methacrylate) (PMMA) targets, one bearing a boron insert. The BeNEdiCTE gamma-ray detector measured an increase in the 478 keV signal of 45 ± 7% and 26 ± 2% for carbon and helium ion irradiation, respectively. Our Geant4 Monte Carlo simulation model, developed to investigate photon origins, found less than 30% of detected photons originated from the insert, while boron in the detector’s circuit boards contributed over 65%. Further, the model investigated detector sensitivity, establishing its capability to record a 10% increase in 478 keV photon detection at a target 10\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{10}$$\\end{document}B concentration of 500 ppm using spectral windowing alone, and 25% when combined with temporal windowing. The linear response extended to concentrations up to 20,000 ppm. The increase in the signal in all evaluated cases confirm the potential of the proposed detector design for neutron capture quantification in NCEPT.

Beam delivery characteristics of the Hitachi carbon ion scanning system at Osaka Heavy Ion Medical Accelerator in Kansai (HIMAK).

Using the pencil beam raster scanning method employed at most carbon beam treatment facilities, spots can be moved without interrupting the beam, allowing for the delivery of a dose between spots (move dose). This technique is also known as Dose-Driven-Continuous-Scanning (DDCS). To minimize its impact on HIMAK patient dosimetry, there's an upper limit to the move dose. Spots within a layer are grouped into sets, or "break points," allowing continuous irradiation. The beam is turned off when transitioning between sets or at the end of a treatment layer or spill. The control system beam-off is accomplished by turning off the RF Knockout (RFKO) extraction and after a brief delay the High Speed Steering Magnet (HSST) redirects the beam transport away from isocenter to a beam dump. The influence of the move dose and beam on/off control on the dose distribution and irradiation time was evaluated by measurements never before reported and modelled for Hitachi Carbon DDCS. We conducted fixed-point and scanning irradiation experiments at three different energies, both with and without breakpoints. For fixed-point irradiation, we utilized a 2D array detector and an oscilloscope to measure beam intensity over time. The oscilloscope data enabled us to confirm beam-off and beam-on timing due to breakpoints, as well as the relative timing of the RFKO signal, HSST signal, and dose monitor (DM) signals. From these measurements, we analyzed and modelled the temporal characteristics of the beam intensity. We also developed a model for the spot shape and amplitude at isocenter occurring after the beam-off signal which we called flap dose and its dependence on beam intensity. In the case of scanning irradiation, we measured move doses using the 2D array detector and compared these measurements with our model. We observed that the most dominant time variation of the beam intensity was at 1 kHz and its harmonic frequencies. Our findings revealed that the derived beam intensity cannot reach the preset beam intensity when each spot belongs to different breakpoints. The beam-off time due to breakpoints was approximately 100 ms, while the beam rise time and fall time (tdecay ) were remarkably fast, about 10 ms and 0.2 ms, respectively. Moreover, we measured the time lag (tdelay ) of approximately 0.2 ms between the RFKO and HSST signals. Since tdelay ≈ tdecay at HIMAK then the HSST is activated after the residual beam intensity, resulting in essentially zero flap dose at isocenter from the HSST. Our measurements of the move dose demonstrated excellent agreement with the modelled move dose. We conducted the first move dose measurement for a Hitachi Carbon synchrotron, and our findings, considering beam on/off control details, indicate that Hitachi's carbon synchrotron provides a stable beam at HIMAK. Our work suggests that measuring both move dose and flap dose should be part of the commissioning process and possibly using our model in the Treatment Planning System (TPS) for new facilities with treatment delivery control systems with higher beam intensities and faster beam-off control.

Monte Carlo-calculated beam quality and perturbation correction factors validated against experiments for Farmer and Markus type ionization chambers in therapeutic carbon-ion beams

Objective. In current dosimetry protocols, the estimated uncertainty of the measured absorbed dose to water D w in carbon-ion beams is approximately 3%. This large uncertainty is mainly contributed by the standard uncertainty of the beam quality correction factor k Q. In this study, the k Q values in four cylindrical chambers and two plane-parallel chambers were calculated using Monte Carlo (MC) simulations in the plateau region. The chamber-specific perturbation correction factor P of each chamber was also determined through MC simulations. Approach. k Q for each chamber was calculated using MC code Geant4. The simulated k Q ratios in subjected chambers and reference chambers were validated through comparisons against our measured values. In the measurements in Heavy-Ion Medical Accelerator in Chiba, k Q ratios were obtained from D w values of 60Co, 290- and 400 MeV u−1 carbon-ion beams that were measured with the subjected ionization chamber and the reference chamber. In the simulations, f Q (the product of the water-to-air stopping power ratio and P) was acquired from D w and the absorbed dose to air calculated in the sensitive volume of each chamber. k Q values were then calculated from the simulated f Q and the literature-extracted W air and compared with previous publications. Main results. The calculated k Q ratios in the subjected chambers to the reference chamber agreed well with the measured k Q ratios. The k Q uncertainty was reduced from the current recommendation of approximately 3% to 1.7%. The P values were close to unity in the cylindrical chambers and nearly 1% above unity in the plane-parallel chambers. Significance. The k Q values of carbon-ion beams were accurately calculated in MC simulations and the k Q ratios were validated through ionization chamber measurements. The results indicate a need for updating the current recommendations, which assume a constant P of unity in carbon-ion beams, to recommendations that consider chamber-induced differences.

Design of a compact superconducting accelerator for advanced heavy-ion therapy

Radiotherapy using energetic carbon beams from the Heavy Ion Medical Accelerator in Chiba (HIMAC) has been carried out at the National Institutes of Quantum Science and Technology (QST) since June 1994. Based on positive clinical results, carbon-ion radiotherapy was authorized as an Advanced Medical Technology by Japanese government from 2003 and it was subsequently approved for inclusion in the Japanese National Health Insurance system from 2016. For the widespread use of carbon-ion radiotherapy, design studies as well as related research and development projects were conducted to develop a compact accelerator facility from 2004. Based on these studies, five compact facilities were constructed in Japan. However, since the accelerators are large in size, construction of these facilities is currently limited to university hospitals or large medical centers, and hence development of a more compact accelerator is desired. To further promote widespread proliferation of heavy-ion facilities and concurrently to maximize the potential of heavy-ion therapy, a project to develop a compact superconducting accelerator, the Quantum Scalpel project, was proposed. The compact accelerator employs superconducting technology to reduce the footprint of the entire accelerator system and the accelerator can provide various therapeutic beams of helium, carbon, oxygen, and neon ions having the energy of 56-430 MeV/u to advanced heavy-ion therapy. In this article, we report the design of the compact superconducting accelerator for the advanced heavy-ion therapy and describe the progress of related research and development projects.

Mass-resolved ion measurement by particle counting analysis for characterizing relativistic ion beams driven by lasers.

Particle counting analysis is a possible way to characterize GeV-scale, multi-species ions produced in laser-driven experiments. We present a multi-layered scintillation detector to differentiate multi-species ions of different masses and energies. The proposed detector concept offers potential advantages over conventional diagnostics in terms of (1) high sensitivity to GeV ions, (2) realtime analysis, and (3) the ability to differentiate ions with the same charge-to-mass ratio. A novel choice of multiple scintillators with different ion stopping powers results in a significant difference in energy deposition between the scintillators, allowing accurate particle identification in the GeV range. Here, we report a successful demonstration of particle identification for heavy ions, performed at the Heavy Ion Medical Accelerator in Chiba. In the experiment, the proposed detector setup showed the ability to differentiate particles with similar atomic numbers, such as C6+ and O8+ ions, and provided an excellent energy resolution of 0.41%-1.2% (including relativistic effect, 0.51%--1.6%).

An inception network for positron emission tomography based dose estimation in carbon ion therapy

Objective. We aim to evaluate a method for estimating 1D physical dose deposition profiles in carbon ion therapy via analysis of dynamic PET images using a deep residual learning convolutional neural network (CNN). The method is validated using Monte Carlo simulations of 12C ion spread-out Bragg peak (SOBP) profiles, and demonstrated with an experimental PET image. Approach. A set of dose deposition and positron annihilation profiles for monoenergetic 12C ion pencil beams in PMMA are first generated using Monte Carlo simulations. From these, a set of random polyenergetic dose and positron annihilation profiles are synthesised and used to train the CNN. Performance is evaluated by generating a second set of simulated 12C ion SOBP profiles (one 116 mm SOBP profile and ten 60 mm SOBP profiles), and using the trained neural network to estimate the dose profile deposited by each beam and the position of the distal edge of the SOBP. Next, the same methods are used to evaluate the network using an experimental PET image, obtained after irradiating a PMMA phantom with a 12C ion beam at QST’s Heavy Ion Medical Accelerator in Chiba facility in Chiba, Japan. The performance of the CNN is compared to that of a recently published iterative technique using the same simulated and experimental 12C SOBP profiles. Main results. The CNN estimated the simulated dose profiles with a mean relative error (MRE) of 0.7% ± 1.0% and the distal edge position with an accuracy of 0.1 mm ± 0.2 mm, and estimate the dose delivered by the experimental 12C ion beam with a MRE of 3.7%, and the distal edge with an accuracy of 1.7 mm. Significance. The CNN was able to produce estimates of the dose distribution with comparable or improved accuracy and computational efficiency compared to the iterative method and other similar PET-based direct dose quantification techniques.

Feasibility of triple gamma ray imaging of 10C for range verification in ion therapy

Objective. In carbon ion therapy, the visualization of the range of incident particles in a patient body is important for treatment verification. In-beam positron emission tomography (PET) imaging is one of the methods to verify the treatment in ion therapy due to the high quality of PET images. We have shown the feasibility of in-beam PET imaging of radioactive 15O and 11C ion beams for range verification using our OpenPET system. Recently, we developed a whole gamma imager (WGI) that can simultaneously work as PET, single gamma ray and triple gamma ray imaging. The WGI has high potential to detect the location of 10C, which emits positrons with a simultaneous gamma ray of 718 keV, within the patient’s body during ion therapy. Approach. In this work, we focus on investigating the performance of WGI for 10C imaging and its feasibility for range verification in carbon ion therapy. First, the performance of the WGI was studied to image a 10C point source using the Geant4 toolkit. Then, the feasibility of WGI was investigated for an irradiated polymethyl methacrylate (PMMA) phantom with a 10C ion beam at the carbon therapy facility of the Heavy Ion Medical Accelerator in Chiba. Main results. The average spatial resolution and sensitivity for the simulated 10C point source at the centre of the field of view were 5.5 mm FWHM and 0.010%, respectively. The depth dose of the 10C ion beam was measured, and the triple gamma image of 10C nuclides for an irradiated PMMA phantom was obtained by applying a simple back projection to the detected triple gammas. Significance. The shift between Bragg peak position and position of the peak of the triple gamma image in an irradiated PMMA phantom was 2.8 ± 0.8 mm, which demonstrates the capability of triple gamma imaging using WGI for range verification of 10C ion beams.

Development of the DICOM-based Monte Carlo dose reconstruction system for a retrospective study on the secondary cancer risk in carbon ion radiotherapy

Objective. A retrospective study on secondary cancer risk on carbon ion radiotherapy (CIRT) is ongoing at the Heavy Ion Medical Accelerator in Chiba (HIMAC). The reconstruction of the whole-body patient dose distribution is the key issue in the study because dose distribution only around the planning target volume was evaluated in the treatment planning system. Approach. We therefore developed a new dose reconstruction system based on the Particle and Heavy Ion Transport code System (PHITS) coupled with the treatment plan DICOM data set by extending the functionalities of RadioTherapy package based on PHITS (RT-PHITS). In the system, the geometry of patient-specific beam devices such as the range shifter, range compensator, and collimators as well as the individual patient’s body are automatically reconstructed. Various functions useful for retrospective analysis on the CIRT are implemented in the system, such as those for separately deducing dose contributions from different secondary particles and their origins. Main results. The accuracy of the developed system was validated by comparing the dose distribution to the experimental data measured in a water tank and using a treatment plan on an anthropomorphic phantom. Significance. The extended RT-PHITS will be used in epidemiological studies based on clinical data from HIMAC.

Introduction and implementation of the CMRP radiodosimeter — a novel wireless microdosimetry system

Microdosimetry is a useful method to evaluate the relative biological effectiveness (RBE) as well as dose equivalent of any mixed radiation field without prior knowledge of type of charged particles and their spectra. The need of portable, user friendly devices for microdosimetric Quality Assurance measurements in particle therapy are greatly preferable to avoid sophisticated setup and time-consuming data analysis.Currently, the ability to perform microdosimetric measurements is restricted to those with extensive prior knowledge of the electronics involved and their experimental setup.The Centre for Medical Radiation Physics (CMRP) has developed a compact microdosimetric system named Radiodosimeter - a novel acquisition system that combines both wireless communication and plug-and-play design to provide a device that can be used with minimal setup. The system is compatible with current CMRP MicroPlus probe technology. The Radiodosimeter communicates with the client computer via Wi-Fi, allowing remote management and monitoring of acquisitions.The system was bench-marked against the standard microdosimetric setup at Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan and was found to have the same response. Several redundancy methods were demonstrated such as continuing an acquisition following disconnection from the client software and the ability to connect through different Wi-Fi modes (WPA2 Personal/Enterprise).These features prove that the Radiodosimeter can operate independently of a client computer, indicating its potential to be used as a portable device for personal monitoring in mixed radiation fields, including for microdosimetric quantity verification predicted by Treatment Planning Software in particle therapy.

Effects of Ionizing Radiation and Long-Term Storage on Hydrated vs. Dried Cell Samples of Extremophilic Microorganisms.

A main factor hampering life in space is represented by high atomic number nuclei and energy (HZE) ions that constitute about 1% of the galactic cosmic rays. In the frame of the “STARLIFE” project, we accessed the Heavy Ion Medical Accelerator (HIMAC) facility of the National Institute of Radiological Sciences (NIRS) in Chiba, Japan. By means of this facility, the extremophilic species Haloterrigena hispanica and Parageobacillus thermantarcticus were irradiated with high LET ions (i.e., Fe, Ar, and He ions) at doses corresponding to long permanence in the space environment. The survivability of HZE-treated cells depended upon either the storage time and the hydration state during irradiation; indeed, dry samples were shown to be more resistant than hydrated ones. With particular regard to spores of the species P. thermantarcticus, they were the most resistant to irradiation in a water medium: an analysis of the changes in their biochemical fingerprinting during irradiation showed that, below the survivability threshold, the spores undergo to a germination-like process, while for higher doses, inactivation takes place as a consequence of the concomitant release of the core’s content and a loss of integrity of the main cellular components. Overall, the results reported here suggest that the selected extremophilic microorganisms could serve as biological model for space simulation and/or real space condition exposure, since they showed good resistance to ionizing radiation exposure and were able to resume cellular growth after long-term storage.

Proton radiation hardness of x-ray SOI pixel sensors with pinned depleted diode structure

X-ray silicon-on-insulator (SOI) pixel sensors, “XRPIX,” are being developed for the next-generation x-ray astronomical satellite, “FORCE.” The XRPIX is fabricated with the SOI technology, which makes it possible to integrate a high-resistivity Si sensor and a low-resistivity Si complementary metal oxide semiconductor (CMOS) circuit. The CMOS circuit in each pixel is equipped with a trigger function, allowing us to read out outputs only from the pixels with x-ray signals at the timing of x-ray detection. This function thus realizes high throughput and high time resolution, which enables to employ anti-coincidence technique for background rejection. A new series of XRPIX named XRPIX6E developed with a pinned depleted diode (PDD) structure improves spectral performance by suppressing the interference between the sensor and circuit layers. When semiconductor x-ray sensors are used in space, their spectral performance is generally degraded owing to the radiation damage caused by high-energy protons. Therefore, before using an XRPIX in space, it is necessary to evaluate the extent of degradation of its spectral performance by radiation damage. Thus, we performed a proton irradiation experiment for XRPIX6E for the first time at Heavy Ion Medical Accelerator in Chiba in the National Institute of Radiological Sciences. We irradiated XRPIX6E with high-energy protons with a total dose of up to 40 krad, equivalent to 400 years of irradiation in orbit. The 40-krad irradiation degraded the energy resolution of XRPIX6E by 25 ± 3 % , yielding an energy resolution of 260.1 ± 5.6 eV at the full-width half maximum for 5.9 keV X-rays. However, the value satisfies the requirement for FORCE, 300 eV at 6 keV, even after the irradiation. It was also found that the PDD XRPIX has enhanced radiation hardness compared to previous XRPIX devices. In addition, we investigated the degradation of the energy resolution; it was shown that the degradation would be due to increasing energy-independent components, e.g., readout noise.

Carbon ion radiotherapy using fiducial markers for prostate cancer in Osaka HIMAK: Treatment planning.

PurposeCarbon ion radiotherapy for prostate cancer was performed using two fine needle Gold Anchor (GA) markers for patient position verification in Osaka Heavy Ion Medical Accelerator in Kansai (Osaka HIMAK). The present study examined treatment plans for prostate cases using beam‐specific planning target volume (bsPTV) based on the effect of the markers on dose distribution and analysis of target movements.Materials and MethodsGafchromic EBT3 film was used to measure dose perturbations caused by markers. First, the relationships between the irradiated film density and absolute dose with different linear energy transfer distributions within a spread‐out Bragg peak (SOBP) were confirmed. Then, to derive the effect of markers, two types of markers, including GA, were placed at the proximal, center, and distal depths within the same SOBP, and dose distributions behind the markers were measured using the films. The amount of internal motion of prostate was derived from irradiation results and analyzed to determine the margins of the bsPTV.ResultsThe linearity of the film densities against absolute doses was constant within the SOBP and the amount of dose perturbations caused by the markers was quantitatively estimated from the film densities. The dose perturbation close behind the markers was smallest (<10% among depths within the SOBP regardless of types of markers) and increased with depth. The effect of two types of GAs on dose distributions was small and could be ignored in the treatment planning. Based on the analysis results of internal motions of prostate, required margins of the bsPTV were found to be 8, 7, and 7 mm in left–right (LR), anterior–posterior (AP), and superior–inferior (SI) directions, respectively.ConclusionWe evaluated the dose reductions caused by markers and determined the margins of the bsPTV, which was applied to the treatment using fiducial markers, using the analysis results of prostate movements.

Effects of LET on oxygen-dependent and-independent generation of hydrogen peroxide in water irradiated by carbon-ion beams

Linear energy transfer (LET) dependence of yields of O2-dependent and O2-independent hydrogen peroxide (H2O2) in water irradiated by ionizing radiation was investigated. The radiation-induced hydroxyl radical (•OH) generation in an aqueous solution was reported to occur in two different localization densities, the milli-molar (relatively sparse) and/or molar (markedly-dense) levels. In the milli-molar-level •OH generation atmosphere, •OH generated at a molecular distance of ∼7 nm are likely unable to interact. However, in the molar-level •OH generation atmosphere, several •OH were generated with a molecular distance of 1 nm or less, and two •OH can react to directly make H2O2. An aliquot of ultra-pure water was irradiated by 290-MeV/nucleon carbon-ion beams at the Heavy-Ion Medical Accelerator in Chiba (HIMAC, NIRS/QST, Chiba, Japan). Irradiation experiments were performed under aerobic or hypoxic (<0.5% oxygen) conditions, and several LET conditions (13, 20, 40, 60, 80, or >100 keV/μm). H2O2 generation in irradiated samples was estimated by three methods. The amount of H2O2 generated per dose was estimated and compared. O2-independent H2O2 generation, i.e. H2O2 generation under hypoxic conditions, increased with increasing LET. On the other hand, the O2-dependent H2O2 generation, i.e. subtraction of H2O2 generation under hypoxic conditions from H2O2 generation under aerobic conditions, decreased with increasing LET. This suggests that the markedly-dense •OH generation is positively correlated with LET. High-LET beams generate H2O2 in an oxygen-independent manner.

Protective Effects of Amino Acids on Plasmid DNA Damage Induced by Therapeutic Carbon Ions.

Radioprotectors with few side effects are useful for carbon-ion therapy, which directly induces clustering damage in DNA. With the aim of finding the most effective radioprotector, we investigated the effects of selected amino acids which might have chemical DNA-repair functions against therapeutic carbon ions. In the current study, we employed five amino acids: tryptophan (Trp), cysteine (Cys), methionine (Met), valine (Val) and alanine (Ala). Samples of supercoiled pBR322 plasmid DNA with a 17 mM amino acid were prepared in TE buffer (10 mM Tris, 1 mM ethylenediaminetetraacetic acid, pH 7.5). Phosphate buffered saline (PBS) was also used in assays of the 0.17 mM amino acid. The samples were irradiated with carbon-ion beams (290 MeV/u) on 6 cm spread-out Bragg peak at the National Institute of Radiological Sciences and Heavy Ion Medical Accelerator in Chiba, Japan. Breaks in the DNA were detected as changes in the plasmids and quantified by subsequent electrophoresis on agarose gels. DNA damage yields and protection factors for each amino acid were calculated as ratios relative to reagent-free controls. Trp and Cys showed radioprotective effects against plasmid DNA damage induced by carbon-ion beam, both in PBS and TE buffer, comparable to those of Met. The double-strand break (DSB) yields and protective effects of Trp were comparable to those of Cys. The yields of both single-strand breaks and DSBs correlated with the scavenging capacity of hydroxyl radicals (rate constant for scavenging hydroxyl radicals multiplied by the amino acid concentration) in bulk solution. These data indicate that the radioprotective effects of amino acids against plasmid DNA damage induced by carbon ions could be explained primarily by the scavenging capacity of hydroxyl radicals. These findings suggest that some amino acids, such as Trp, Cys and Met, have good potential as radioprotectors for preventing DNA damage in normal tissues in carbon-ion therapy.

Effects of loading a magnetic field longitudinal to the linear particle-beam track on yields of reactive oxygen species in water

The effects of a magnetic field longitudinal to the ion beam track on the generation of hydroxyl radicals (•OH) and hydrogen peroxide (H2O2) in water were investigated. A longitudinal magnetic field was reported to enhance the biological effects of the ion beam. However, the mechanism of the increased cell death by a longitudinal magnetic field has not been clarified. The local density of •OH generation was estimated by a method based on the EPR spin-trapping. A series of reaction mixtures containing varying concentrations (0.76‒2278 mM) of DMPO was irradiated by 16 Gy of carbon- or iron-ion beams at the Heavy-Ion Medical Accelerator in Chiba (HIMAC, NIRS/QST, Chiba, Japan) with or without a longitudinal magnetic field (0.0, 0.3, or 0.6 T). The DMPO-OH yield in the sample solutions was measured by X-band EPR and plotted versus DMPO density. O2-dependent and O2-independent H2O2 yields were measured. An aliquot of ultra-pure water was irradiated by carbon-ion beams with or without a longitudinal magnetic field. Irradiation experiments were performed under air or hypoxic conditions. H2O2 generation in irradiated water samples was quantified by an EPR spin-trapping, which measures •OH synthesized from H2O2 by UVB irradiation. Relatively sparse •OH generation caused by particle beams in water were not affected by loading a magnetic field on the beam track. O2-dependent H2O2 generation decreased and oxygen-independent H2O2 generation increased after loading a magnetic field parallel to the beam track. Loading a magnetic field to the beam track made •OH generation denser or made dense •OH more reactive.

Characterization of a novel large area microdosimeter system for low dose rate radiation environments

A feasibility study is presented on a newly developed microdosimetry system named Octobox, for its application in low dose rate, mixed radiation environments. A full characterization of the device was performed at the Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan, out-of-field of various heavy ion radiation fields — 290 MeV/u 12C, 230 MeV/u and 490 MeV/u 28Si and 400 MeV/u 20Ne ions, as well as a low dose rate 222Rn environment at the Australian Nuclear Sciences and Technology Organization (ANSTO). The device was shown to collect adequate statistics in a short period of time when compared to the MicroPlus probe with a single microdosimeter, while accurately measuring microdosimetric quantities and the corresponding average quality factor (Q¯) and dose equivalent (H) of the mixed radiation field. Good agreement of the microdosimetric spectra was also shown with Geant4 simulations for all presented ion fields. Based on the findings in this study, the Octobox is capable of being applied in mixed, low dose rate, radiation environments such as those encountered in space and aviation, as well as in underground mines for radiation protection purposes.

Thin cathode glass gas electron multiplier detector for carbon beam dose imaging

ABSTRACT An optically read-out glass gas electron multiplier (G-GEM) detector is expected to simplify complicated quality assurance measurements for hadron therapies by imaging the dose distribution of the incident beam. However, the effect of secondary particles from the detector itself has not been well studied. In this paper, we evaluate a design that reduces the secondary particles from the cathode of a G-GEM detector. Specifically, we assembled detectors with thin cathodes and assessed their effect on the secondary particle production in simulations and experiments. The experiments were carried out under 290 MeV/u 12C ion bombardment at the Heavy Ion Medical Accelerator in Chiba. The clinical intensity of the thin cathode detector was compared with that of a conventional thick cathode G-GEM detector. The improved chamber design reduced the dose contributions of secondary particles from the cathode without degrading the dose imaging performance.