Heavy Ion Medical Accelerator In Chiba Research Articles

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.

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 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.

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.

Biologic Impact of Different Ultra-Low-Fluence Irradiations in Human Fibroblasts.

In this study, we aimed to evaluate the cellular response of healthy human fibroblasts induced by different types of ultra-low-fluence radiations, including gamma rays, neutrons and high linear energy transfer (LET) heavy ions. NB1RGB cells were pretreated with ultra-low-fluence radiations (~0.1 cGy/7–8 h) of 137Cs gamma rays, 241Am–Be neutrons, helium, carbon and iron ions before being exposed to an X-ray-challenging dose (1.5 Gy). Helium (LET = 2.3 keV/µm), carbon (LET = 13.3 keV/µm) and iron (LET = 200 keV/µm) ions were generated with the Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan. No differences in cell death—measured by colony-forming assay—were observed regardless of the radiation type applied. In contrast, mutation frequency, which was detected through cell transformation into 6-thioguanine resistant clones, was 1.9 and 4.0 times higher in cells pretreated with helium and carbon ions, respectively, compared to cells exposed to X-ray-challenging dose alone. Moreover, cells pretreated with iron ions or gamma-rays showed a mutation frequency similar to cells exposed to X-ray-challenging dose alone, while cells pretreated with neutrons had 0.15 times less mutations. These results show that cellular responses triggered by ultra-low-fluence irradiations are radiation-quality dependent. Altogether, this study shows that ultra-low-fluence irradiations with the same level as those reported in the International Space Station are capable of inducing different cellular responses, including radio-adaptive responses triggered by neutrons and genomic instability mediated by high-LET heavy ions, while electromagnetic radiations (gamma rays) seem to have no biologic impact.

Experimental investigation of the characteristics of radioactive beams for heavy ion therapy.

This work has two related objectives. The first is to estimate the relative biological effectiveness of two radioactive heavy ion beams based on experimental measurements, and compare these to the relative biological effectiveness of corresponding stable isotopes to determine whether they are therapeutically equivalent. The second aim is to quantitatively compare the quality of images acquired postirradiation using an in-beam whole-body positron emission tomography scanner for range verification quality assurance. The energy deposited by monoenergetic beams of C at 350MeV/u, O at 250MeV/u, C at 350MeV/u, and O at 430MeV/u was measured using a cruciform transmission ionization chamber in a water phantom at the Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan. Dose-mean lineal energy was measured at various depths along the path of each beam in a water phantom using a silicon-on-insulator mushroom microdosimeter. Using the modified microdosimetric kinetic model, the relative biological effectiveness at 10% survival fraction of the radioactive ion beams was evaluated and compared to that of the corresponding stable ions along the path of the beam. Finally, the postirradiation distributions of positron annihilations resulting from the decay of positron-emitting nuclei were measured for each beam in a gelatin phantom using the in-beam whole-body positron emission tomography scanner at HIMAC. The depth of maximum positron-annihilation density was compared with the depth of maximum dose deposition and the signal-to-background ratios were calculated and compared for images acquired over 5 and 20min postirradiation of the phantom. In the entrance region, the was 1.2±0.1 for both C and C beams, while for O and O it was 1.4±0.1 and 1.3±0.1, respectively. At the Bragg peak, the was 2.7±0.4 for C and 2.9±0.4 for C, while for O and O it was 2.7±0.4 and 2.8±0.4, respectively. In the tail region, could only be evaluated for carbon; the was 1.6±0.2 and 1.5±0.1 for C and C, respectively. Positron emission tomography images obtained from gelatin targets irradiated by radioactive ion beams exhibit markedly improved signal-to-background ratios compared to those obtained from targets irradiated by nonradioactive ion beams, with 5-fold and 11-fold increases in the ratios calculated for the O and C images compared with the values obtained for O and C, respectively. The difference between the depth of maximum dose and the depth of maximum positron annihilation density is 2.4±0.8mm for C, compared to -5.6±0.8mm for C and 0.9±0.8mm for O vs -6.6±0.8mm for O. The values for C and O were found to be within the 95% confidence interval of the RBEs estimated for their corresponding stable isotopes across each of the regions in which it was evaluated. Furthermore, for a given dose, C and O beams produce much better quality images for range verification compared with C and O, in particular with regard to estimating the location of the Bragg peak.

Experimental verification of beam switching operation for multiple-ion therapy applications at HIMAC

A study of multiple-ion therapy with charged heavy-ion beams was performed to improve outcomes of refractory cancer treatments. We proposed the accelerator operation method for applying the multiple-ion therapy, to quickly switch the ion species and energies of the output beams. In this method, the irradiation ion species can be changed only by switching the selected ion source and the injector parameters, and the output beam energies can be varied without changing the magnetic operation patterns of the synchrotron. We verified the effectiveness of our approach by conducting experiments at the Heavy Ion Medical Accelerator in Chiba (HIMAC) and confirmed that the approach can provide the fast switching of both the ion species and the beam energies. The experimental results also demonstrated that our approach will greatly reduce the commissioning time and the routine adjustments for multiple-ion beams.

The Immunomodulatory Effects of Carbon-Ion Therapy on Solid Tumors

Radiation-induced immunostimulation is of great interest as a focal strategy to reinvigorate or augment an immunotherapy-induced tumor-specific response. While evidence supports photon therapy (PhRT) as a tumor immunomodulator, pre-clinical data suggest that carbon-ion therapy (CiRT) may be more potent. Here we evaluate the immunomodulatory effects of CiRT, compared to biologically equivalent doses (BEDs) of PhRT, in a breast cancer mouse model. Using the orthotopic 4T1 mouse breast cancer model, we evaluated the immunomodulatory effects of very low (0.4 Gy), low (1 Gy) and high (4 Gy) doses of CiRT (290 MeV/u, SOBP) delivered to mammary tumors at the Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan compared to BEDs (RBE 2) of PhRT (SARRP, Xstrahl; 220 kV). Primary tumors were treated 7-days post implantation and harvested 72-hours later for flow cytometric characterization of tumor-infiltrating lymphocytes. Low (1 Gy) and high-dose (4 Gy) CiRT resulted in a 32% and 51% (p<0.01) decrease in CD4+ T-cells, with no significant change following very low-dose (0.4 Gy) CiRT. Whereas, very low, low, and high-dose PhRT reduced CD4+ T-cells by 50%, 32% and 44% (p<0.05) and very low and high-dose PhRT reduced CD8+ T-cells by 55% and 47% (p<0.05), compared to control. Very high-dose (4 Gy) CiRT induced a 184% and 117% (p<0.05) increase in proliferation (Ki67+) by CD4+ and CD8+ T-cells, respectively, compared to control. While, very low, low and high-dose PhRT increased proliferation of CD4+ T-cells by 170%, 129% and 216% (p<0.05) and CD8+ T-cells by 84%, 86% and 99% (p<0.05), compared to control. High-dose (4 Gy) CiRT induced pro-inflammatory cytokines production including granzyme B (88%, 205% increase; P<0.005), IL-2 (112%, 165% increase, p<0.01) and TNF-a (230%, 117%, p<0.005) by CD4+ and CD8+ T-cells, respectively, with no change in IFN-g expression. Whereas, high-dose PhRT increased IFN-g expression by 102% (p<0.05) by CD8+ T-cells, with no change in granzyme B, IL-2, or TNF-a. Only high-dose (4 Gy) CiRT induced a 127% increase (p<0.005) in abundance and a 70% (p<0.05) increase proliferation of immunosuppressive regulatory T-cells (Tregs), whereas very low and high-dose PhRT increased proliferation of Tregs by 82% and 99% (p<0.05), respectively, with no increase in abundance. These data suggest that at low doses, lymphocytes differ in their sensitivity to CiRT compared to PhRT, whereby very low dose CiRT is lymphocyte-sparing. Very high-dose CiRT and PhRT induced immunostimulatory effects by differing degrees and through different mechanisms, CiRT being more potent and inducing changes in a diverse set of pro-inflammatory cytokines including granzyme B, IL-2 and TNF-a, whereas PhRT induced only IFN-g. Combining less lymphotoxicity at low doses with a more potent and mechanistically diverse pro-inflammatory effects at high doses, CiRT may be a more optimal synergistic tool to augment an immunotherapy-induced, tumor-specific response.

Radiation-induced redox alteration in the mouse brain

Time courses of the redox status in the brains of mice after X-ray or carbon-ion beam irradiation were observed by magnetic resonance redox imaging (MRRI). The relationship between radiation-induced oxidative stress on the cerebral nervous system and the redox status in the brain was discussed.The mice were irradiated by 8-Gy X-ray or carbon-ion beam (C-beam) on their head under anesthesia. C-beam irradiation was performed at HIMAC (Heavy-Ion Medical Accelerator in Chiba, NIRS/QST, Chiba, Japan). MRRI measurements using a blood-brain-barrier-permeable nitroxyl contrast agent, MCP or TEMPOL, were performed using 7-T scanner at several different times, i.e., 5–10 h, 1, 2, 4, and 8 day(s) after irradiation. Decay rates of the nitroxyl-enhanced T1-weighted MR signals in the brains were estimated from MRRI data sets, and variation in the decay rates after irradiation was assessed.The variation in decay rates of MCP and TEMPOL after X-ray or C-beam irradiation was similar, but different variation patterns were observed between X-ray and C-beam. The apparent decay rate of both MCP and TEMPOL decreased due to the temporal reduction of blood flow in the brain several hours after X-ray and/or C-beam irradiation. After decreasing, the apparent decay rates of nitroxyl radicals in the brain gradually increased during the following days after X-ray irradiation or rapidly increased 1 day after C-beam irradiation. The sequential increase in nitroxyl decay rates may have been due to the oxidative atmosphere in the tissue due to ROS generation. X-ray and C-beam irradiation resulted in different redox responses, which may have been due to time-varying oxidative stress/injury, in the mouse brain. The C-beam irradiation effects were more acute and larger than those of X-ray irradiation.

Development of an HTS Accelerator Magnet With REBCO Coils for Tests at HIMAC Beam Line

An R&D project funded by the Japan Science and Technology Agency under its S-Innovation Program is currently in progress. The purpose of this project is to develop fundamental technologies for accelerator magnets with REBCO coils. In the first step of this project, winding technology for fabricating REBCO coils required for HTS accelerator magnets was developed. At the last stage of this project, there are plans to fabricate cryocooler-cooled REBCO magnets and evaluate the beam guiding characteristics and stability against beam injection to the magnets at the beam line of Heavy Ion Medical Accelerator in Chiba (HIMAC). This paper describes the design of an HTS magnet fabricated for this evaluation and presents fabrication results of this magnet. The magnet had a room-temperature beam duct with dimensions 264× 40 mm for beam guiding. The magnet consisted of a pair of racetrack coil stacks each containing four coils, and a cold iron was adopted to increase the magnetic field strength. It could generate a dipole field of 2.4 T at the beam duct by 200 A excitation. Furthermore, beam windows were placed on the side of the cryostat for beam injection tests, allowing the beam to irradiate the REBCO coil directly.

Range verification of radioactive ion beams of 11C and 15O using in-beam PET imaging

In advanced ion therapy, the visualization of the range of incident ions in a patient’s body is important for exploiting the advantages of this type of therapy. It is ideal to use radioactive ion beams for in-beam positron emission tomography (PET) imaging in particle therapy due to the high quality of PET images caused by the high signal-to-noise ratio. We have shown the feasibility of this idea through an in-beam PET study for 11C and 15O ion beams using the dedicated OpenPET system. In this work, we investigate the potential difference between the Bragg peak position and the position of the maximum detected positron-emitting fragments by a PET system for the radioactive beams of 11C and 15O. For this purpose, we measured the depth dose in a water phantom and performed PET scans of an irradiated PMMA phantom for the available beams of 11C and 15O at the Heavy Ion Medical Accelerator in Chiba (HIMAC). Then, we simulated the depth dose profiles in the water phantom and the yield of the positron-emitting fragments in a PMMA phantom for both available beams using the Monte Carlo code PHITS. The positions of the Bragg peak and maximum positron-emitting fragments from the measurements were well reproduced by simulation. The effect of beam energy broadening on the positional differences between two peaks was studied by simulating an irradiated PMMA phantom. The differences in position between the Bragg peak and the maximum positron-emitting fragments increased when the beam energy spread was broadened, although the differences were zero for the ideal mono-energetic beams. Greater differences were observed for 11C ion beams compared to 15O ion beams, although both beams had the same range in water, and the higher energy corresponded to a larger difference. For the known energy spread of the beams, the predicted differences between two peaks from the simulation were consistent with the measured data within submillimetre agreement.

Optical imaging for the characterization of radioactive carbon and oxygen ion beams

Heavy ion therapy is a promising cancer therapy technique due to the sharper Bragg peak and smaller lateral scattering characteristics of heavy ion beams as compared to a proton therapy. Recently, the potential for radioactive ion beam therapy has been investigated in combination with the OpenPET system to improve the accuracy of in vivo beam range verification. However, the characteristics of the radioactive ion beams have not been investigated thoroughly. Optical imaging has been proposed as a novel high-resolution beam range estimation method for heavy ion beams. In this study, high-resolution luminescence imaging and Cerenkov light imaging were performed for the range estimation of radioactive ion beams such as 11C and 15O in the Heavy Ion Medical Accelerator in Chiba (HIMAC) secondary beam line. A polymethyl methacrylate (PMMA) phantom (10.0 × 10.0 × 9.9 cm3) was irradiated by 11C and 15O ion beams. In order to obtain the in-beam luminescence and off-line beam Cerenkov light images, an optical system was used that consisted of a lens and a cooled CCD camera. The Bragg peaks and stopping positions of the 11C and 15O ion beams could be visualized by using the luminescence and Cerenkov light imaging, respectively. The Bragg peaks showed a good correlation with the peak of the luminescence profile with a positional discrepancy of 1 mm and 0.4 mm for the 11C and 15O ion beams, respectively. In conclusion, optical imaging using luminescence and Cerenkov light could be used for the precise range estimation of radioactive ion beams.

Temperature dependence of ionization quenching in BGO scintillators

Scintillation detectors are commonly used as radiation detectors. For the detection of heavy ions a non-linearity in scintillation light output is observed which is known as ionization quenching. In this paper we investigate whether the ionization quenching for BGO scintillators depends on temperature. This would impact the validity of ionization quenching correction models in temperature unstable environments. We measured temperature dependent light output curves for several ion species at different energies at the Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan. We find that the normalized temperature dependent light output curves show the same temperature dependence for all ion species and energies. Therefore, we conclude that the effect of ionization quenching in BGO is independent of temperature. Thus the temperature dependence of scintillation light output and the effect of ionization quenching are independent and can be separately correct by the already developed models for the scintillation light output of BGO.

3D sensitive volume microdosimeter with improved tissue equivalency: charge collection study and its application in 12C ion therapy

This research focuses on the characterisation of a new 3D sensitive volume (SV) microdosimeter covered with polyimide – a material which closely mimics human tissue. The electrical and charge collection properties of the device were investigated and its application in 12C ion therapy were studied. Charge collection studies revealed uniform charge collection and no cross talk between adjacent SVs. To study the microdosimetric response in 12C ion therapy, the new polyimide mushroom microdosimeter were placed at various positions along the central axis of a 290 MeV/u 12C ion spread out Bragg peak (SOBP) at the Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan. From these microdosimetric spectra, dose mean lineal energy and RBE10 results were obtained, with RBE10 increasing from 1.3 at the entrance to 2.7 at the end of the SOBP. The results obtained in this work show that the new generation of mushroom microdosimeters, covered with tissue equivalent polyimide material, are a useful tool for quality assurance in heavy ion therapy applications.

41 Simulation of the biological effectiveness caused by 65 MeV protons (clinical beam) and carbon-ions

Introduction In order to optimize hadron therapy treatments, not only the absorbed dose will be taken in account but the biological consequences on the irradiated cell structures will be considered as well. To achieve that, the relative biological effectiveness (RBE) is estimated to provide the information we need on how cells respond to irradiation. Here we are focusing on a 65 MeV clinical proton beam from the Antoine Lacassagne clinical center in Nice and a 4 MV carbon-ion beam from the Heavy-Ion Medical Accelerator in Chiba (Japan). To predict the said RBE, there are several biophysical models implemented by Monte Carlo codes, some of them already are in use for treatment planifications. Among them, the microkinetic model (MKM) [1] , [2] and the nanOx model are tested in this study. To address this issue, we use the GATE Monte Carlo platform to estimate the biological effectiveness. Methods Are collected survival curves from the cell lines samples according to the linear quadratic model. The cells are irradiated by a reference 250 kVp X-ray beam (delivered by the X-rad 320 X-ray system) a 65 MeV proton beam and a 4MV carbon-ion beam (passive mode), the dose being in a 0 to 10 Gy range. All the beams used to conduct the cell irradiations are entirely emulated with the version 8.0 of the GATE Monte Carlo plateform. The microdosimetric spectrums (or linear energy distribution) are then estimated and implemented to the biophysical models. Results The emulated depth dose distributions and Bragg peaks are verified and consistent with the experimental ionization chamber measurements. The MKM and the NanOx models then predict the biological effectiveness as the said predictions are compared from one model to the other. Conclusions This work lead to the implementation and the validation of the two studied biological models on the GATE simulation plateform. The same methodology will be applicated to more energetic clinical proton and carbon-ion beams.

102 - Comparison of effects of plateau carbon-ion beams and x-rays on the redox states of aqueous and organic solutions of 2,2-diphenyl-1-picrylhydrazyl radical

Carbon-ion (C-ion) beams are known to exhibit a sharp maximum of the energy deposition, called as a Bragg peak, at a certain penetration depth. Thus, the cancer cells are precisely killed by adjusting the Bragg peak to a tumor. However, the dose in the plateau region of the C-ion beams before the Bragg peak is not necessarily zero. In this study, the redox states of aqueous and organic solutions after irradiation by the plateau C-ion beams were evaluated by 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) as a redox probe. Irradiation of the C-ion beams (290 MeV per nucleon, 13 keV µm–1) was carried out using the Heavy Ion Medical Accelerator in Chiba (HIMAC) at National Institute of Radiological Sciences, Japan. A Shimadzu Pantak HF-320 was used for X-irradiation (X-ray tube voltage: 200 kV, X-ray tube current: 20 mA, pre-filter: 0.5 mm Cu + 0.5 mm Al, dose rate: 1.78 Gy min–1). C-ion irradiation of aqueous solutions of DPPH• solubilized by β-cyclodextrin in water resulted in the decrease in the absorption band at 527 nm due to DPPH•. The absorbance at 527 nm linearly decreased with increasing the radiation dose. When C-ion beams were replaced by X-rays, the slope of the linear plot is about the same as that in the case of C-ion beams. Similar results were obtained when H2O was replaced by methanol or acetonitrile without β-cyclodextrin, although the slope values were twice larger as compared to the cases in H2O. On the other hand, DPPH• was more susceptible to the C-ion beams or X-rays in isopropyl myristate (IPM), a saturated fatty acid ester, than in H2O, methanol, and acetonitrile. Furthermore, the C-ion beams consumed DPPH• more effectively than X-rays in IPM, suggesting that lipid molecules may be more susceptible to the C-ion beams than to X-rays. The mechanism will also be discussed based on the product analysis by the electron spin resonance (ESR) spin-trapping.

Low temperature thermoluminescence anomaly of LiF:Mg,Cu,P radiation detectors exposed to 1H and 4He ions

Lithium fluoride thermoluminescent radiation detectors with different dopant concentrations (7LiF:Mg,Ti and 7LiF:Mg,Cu,P) were exposed to 1H and 4He ions at the Heavy Ion Medical Accelerator in Chiba (HIMAC) in order to investigate their response to energetic light charged particles. Computer simulations with the Monte Carlo code PHITS were performed for a better interpretation of the experimental data. The results were compared with literature efficiency data and with the results of a recently developed microdosimetric efficiency model. In case of the main peak signal of 7LiF:Mg,Ti detectors, the determined efficiency values are in good agreement with previous investigations. Discrepancies in the efficiency of high temperature signal due to well-known non-linearity effects are reported. For 7LiF:Mg,Cu,P detectors, an anomalous thermoluminescence behavior in the low temperature part of the signal was found and discussed. Depending on the light quantification process, differences up to 30% in the dose assessment can be obtained, affecting also the relative efficiency determination process. An explanation of this phenomenon as a consequence of local migration of the charged carriers between the low temperature peaks and the main peak is presented. The implications of these findings on the use of LiF:Mg,Cu,P detectors in radiation environments characterized by the presence of 1H and 4He ions (i.e. space and proton therapy) are discussed. In order to avoid the occurrence of this anomalous behavior, it is advised to pre-heat the detectors after energetic light particle exposures.