12C Ion Beams Research Articles

Biological Response of Chinese Hamster B14-150 Cells to Sequential Combined Exposure to Protons and 12C Ions.

Proton and ion radiation therapy, when used both as single radiation and in mixed radiation mode, have a number of advantages over the conventional γ-therapy that are determined by physical characteristics of accelerated particles. The paper presents the results of an in vitro study of the effectiveness of sequential exposures of Chinese hamster tumor cells B14-150 to proton (p) and 12C ion beams. We used 4 irradiation schemes differing by the sequence of exposure and the contribution of each radiation to the total dose. Synergism was shown for 12C ions dose contribution of 45% (taking into account the coefficient of relative biological efficiency) and the sequence 12C→p.

Tumour status prediction by means of carbon-ion beam irradiation: comparison of washout rates between in-beam PET and DCE-MRI in rats

Objective. Tumour response to radiation therapy appears as changes in tumour vascular condition. There are several methods for analysing tumour blood circulatory changes one of which is dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), but there is no method that can observe the tumour vascular condition and physiological changes at the site of radiation therapy. Positron emission tomography (PET) has been applied for treatment verification in charged particle therapy, which is based on the detection of positron emitters produced through nuclear fragmentation reactions in a patient’s body. However, the produced positron emitters are washed out biologically depending on the tumour vascular condition. This means that measuring the biological washout rate may allow evaluation of the tumour radiation response, in a similar manner to DCE-MRI. Therefore, this study compared the washout rates in rats between in-beam PET during 12C ion beam irradiation and DCE-MRI. Approach. Different vascular conditions of the tumour model were prepared for six nude rats. The tumour of each nude rat was irradiated by a 12C ion beam with simultaneous in-beam PET measurement. In 10–12 h, the DCE-MRI experiment was performed for the same six nude rats. The biological washout rate of the produced positron emitters (k 2,1st) and the MRI contrast agent (k 2a) were derived using the single tissue compartment model. Main results. A linear correlation was observed between k 2,1st and k 2a, and they were inversely related to fractional necrotic volume. Significance. This is the first animal study which confirmed the biological washout rate of in-beam PET correlates closely with tumour vascular condition measured with the MRI contrast agent administrated intravenously.

Relative efficiency of radiophotoluminescent glass detectors in low energy ion beams

In heavy charged particle dosimetry, the luminescence efficiency strongly depends on linear energy transfer (LET) and characterization of the detectors' efficiency as a function of the particle LET is very important. Available literature data for the efficiency of radiophotoluminescent (RPL) glass detectors are scarce and especially for low energy range no data was found. In this study, detectors made of the most widely known RPL material (silver activated phosphate glass) were exposed to various low energy ion beams (1H, 7Li, and 12C). For every ion beam, the linear dose (fluence) response of the RPL glass detectors was confirmed for the investigated dose (fluence) range and the RPL efficiency relative to 60Co gamma rays was evaluated. The relative efficiency decreased as LET increased but not as a unique function of LET, where the relative efficiency (expressed for doses in RPL glass) decreased from 0.85 ± 0.06 for the 5 MeV 1H ion beam (LETw = 8.1 keV/μm) to 0.017 ± 0.001 for the 15 MeV 12C ion beam (LETw = 673.8 keV/μm). More experimental data are still needed but results obtained in this study may motivate the application and testing of microdosimetric models for RPL glass detectors.

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.

3D high resolution clonogenic survival measurement of xrs-5 cells in low-dose region of carbon ion plans

Purpose In this study, we performed biological verification measurements of cell survival of a 12C ion irradiation plan employing a high-resolution 3D culture setup. This allowed, in particular, to access the cell inactivation in the low-dose regions close to the target area. Materials and methods We established the protocol for a 3D culture setup where xrs-5 cells were grown inside a layered matrigel structure in 384-well plates. Their radiosensitivity to conventional and 12C ion radiation was evaluated by irradiating them either with 250 kV X-rays at GSI or with monoenergetic 12C beams of 110 MeV/u at MIT, and compared with those of monolayers. A treatment plan for a rectangular target was prepared using the GSI research treatment planning system TRiP98. xrs-5 cells were seeded in the matrigel-based setup and irradiated in dose fall-off regions using active scanning 12C ion beams. In addition, film dosimetry utilizing radiochromic EBT3 film has been performed to assess the field homogeneity downstream of 384-well V-bottom plates with or without additional agarose coating of the well plate bottom. Results Dose response curves following X-ray and 12C ion irradiation had linear shape and showed a significant decrease in survival fraction at even moderate doses. Survival measurements in the low-dose regions of the plan for the extended target showed good agreement to the predicted survival fraction. The irradiated film profiles yielded a flat dose distribution without apparent artifacts or inhomogeneities for well plates both with and without agarose coating, confirming the suitability of the experimental setup. Conclusions We conclude that the V-bottom 384-well plates in combination with the radiation-sensitive xrs-5 cell line constitute a suitable radiobiological verification tool which can be used especially for low doses. Furthermore, the measured survival of xrs-5 cells show a good agreement with the expected survival in the low-dose out-of-field regions, both laterally and downstream of the target.

Physiological and Differential Proteomic Analysis at Seedling Stage by Induction of Heavy-Ion Beam Radiation in Wheat Seeds.

Novel genetic variations can be obtained by inducing mutations in the plant which help to achieve novel traits. The useful mutant can be obtained through radiation mutation in a short period which can be used as a new material to produce new varieties with high yield and good quality wheat. In this paper, the proteomic analysis of wheat treated with different doses of 12C and 7Li ion beam radiation at the seedling stage was carried out through a Tandem Mass Tag (TMT) tagging quantitative proteomic analysis platform based on high-resolution liquid chromatography-mass spectrometry, and the traditional 60Co-γ-ray radiation treatment for reference. A total of 4,764 up-regulated and 5,542 down-regulated differentially expressed proteins were identified. These proteins were mainly enriched in the KEGG pathway associated with amino acid metabolism, fatty acid metabolism, carbon metabolism, photosynthesis, signal transduction, protein synthesis, and DNA replication. Functional analysis of the differentially expressed proteins showed that the oxidative defense system in the plant defense system was fully involved in the defense response after 12C ion beam and 7Li ion beam radiation treatments. Photosynthesis and photorespiration were inhibited after 12C ion beam and 60Co-γ-ray irradiation treatments, while there was no effect on the plant with 7Li ion beam treatment. In addition, the synthesis of biomolecules such as proteins, as well as multiple signal transduction pathways also respond to radiations. Some selected differentially expressed proteins were verified by Parallel Reaction Monitoring (PRM) and qPCR, and the experimental results were consistent with the quantitative results of TMT. The present study shows that the physiological effect of 12C ion beam radiation treatment is different as compared to the 7Li ion beam, but its similar to the 60Co-γ ray depicting a significant effect on the plant by using the same dose. The results of this study will provide a theoretical basis for the application of 12C and 7Li ion beam radiation in the mutation breeding of wheat and other major crops and promote the development of heavy ion beam radiation mutation breeding technology.

Demonstration of an optically stimulated luminescence (OSL) material with reduced quenching for proton therapy dosimetry: MgB4O7:Ce,Li

The objective of this work is to demonstrate that MgB4O7:Ce,Li, a new optically stimulated luminescence (OSL) dosimetric material, shows improved response for proton therapy dosimetry, with less reduction in luminescence detector efficiency with the particle linear energy transfer (LET). MgB4O7:Ce,Li was synthesized and its luminescence efficiency as a function of LET was characterized for dose-averaged LET values from 0.73 keV/μm up to 74.9 keV/μm using proton, 4He, and 12C ion beams. Commercial Al2O3:C OSLDs were also used for comparison. Monte Carlo simulations were used to predict the material's response in pristine and spread-out Bragg peaks (SOBP), suggesting the MgB4O7:Ce,Li would offer minimum quenching in proton beams of energies relevant to radiotherapy. This prediction was confirmed by irradiations of MgB4O7:Ce,Li and Al2O3:C along SOBPs from proton beams. The results demonstrate that new OSL materials optimized for proton dosimetry can be developed using their dose response to low-LET radiation as a guide during material development.

Measurement of reduced radii, depths, and optical densities of pits using computer analysis of micrographs of CR-39 plates etched after irradiation with 12C ion beam

This work is a further development of our method, published in 2018, for computer analysis of micrographs taken from a plastic detector CR-39, etched after irradiation with a beam of 12C ions of energy 216 MeV/amu in the radiobiological research chamber of the ITEP-TWAC accelerator-storage complex. The aim of this work is to study geometric and optical parameters of pits in the etched plastic. This study is based on a new concept of reduced radii, which are the radii of the cross-section of inclined conical micro- and nano-pits at the points of intersection of their longitudinal axes and the etching surface of the detector; formulas for their calculations are derived. One CR-39 plate was irradiated in a radiobiological chamber filled with air, and eight plates were exposed at different depths of the chamber filled with water (phantom). 275,070 images of etched pores were found and analyzed in the plates. Differential frequency distributions of the reduced radii and depths of the pits and their average values on the etched surfaces of the plates are obtained. Formulas for nanodensitometry, microdensitometry, and macrodensitometry of pit images on micrographs are deduced. The dependences of the differential distributions and averaged values of pits optical densities on the ions passed ranges in the water phantom are calculated. Pairwise fittings by linear functions of the mutual dependences of the averaged values from each other and from the specific energy losses of ions are performed. It is shown that the most accurate linear fit is for the optical density-pit depth relationship.

Fluence perturbation from fiducial markers due to edge-scattering measured with pixel sensors for 12C ion beams

Fiducial markers are nowadays a common tool for patient positioning verification before radiotherapy treatment. These markers should be visible on x-ray projection imaging, produce low streak artifacts on CTs and induce small dose perturbations due to edge-scattering effects during the ion-beam therapy treatment. In this study, the latter effect was investigated and the perturbations created by the markers were evaluated with a new measurement method using a tracker system composed of six CMOS pixel sensors. The present method enables the determination of the particle trajectory before and after the target. The experiments have been conducted at the Marburg Ion Beam Therapy Center with carbon ion beams and the measurement concept was validated by comparison with radiochromic films. This work shows that the new method is very efficient and precise to measure the perturbations due to fiducial markers with a tracker system. Three dimensional fluence distributions of all particle trajectories were reconstructed and the maximum cold spots due to the markers and their position along the beam axis were quantified. In this study, four small commercial markers with different geometries and materials (gold and carbon-coated ZrO2) were evaluated. The gold markers showed stronger perturbations than the lower density ones. However, it is important to consider that low density and low atomic number fiducial markers are not always visible on x-ray projections.

Monte Carlo Study of Nuclear Fragmentation in Water Irradiated with Protons and 12C Ions for Particle Therapy Applications

In this study, the nuclear fragmentation of the secondary particles produced when water is irradiated with protons and carbons were investigated. Proton beams with varying incident energies of 100 MeV, 130 MeV, 150 MeV and 160 MeV were used with corresponding 12C ion beams of about 187.50 MeV/u, 241.67 MeV/u, 285.42 MeV/u and 308.33 MeV/u respectively. The kinetic energy distribution and energy deposition of primary and secondary particles were studied via Monte Carlo simulation with the aid of GATE v.8.0 via GEANT4 simulation toolkit version 10.3.2 with 1 x 106 incident beams. The physics list used was QGSP_BIC (Quark Gluon String Pre-compound Binary Cascade). When the primary 12C ion and proton beams interact with water, secondary light-charged and heavy-charged particles are produced with atomic number Z > 2 are produced. In general, it was shown that the incident 12C ions are less scattered as they traverse mater compared to the incident protons. Thus, the energy deposition of 12C ions is well-defined and is better in terms of conformation.

Experimental verification of a non-invasive method to monitor the lateral pencil beam position in an anthropomorphic phantom for carbon-ion radiotherapy

The dose conformation and the sparing of neighboring critical healthy structures are improved in carbon-ion beam radiotherapy in comparison to conventional photon radiotherapy. Inter and intrafractional plan adaptation strategies may preclude the quality assurance (QA) of the actually applied treatment plan before the treatment starts. Therefore, independent measurements of the positions of scanned pencil 12C ion beams are of interest in order to monitor the beam application during the treatment and the beam in the isocenter. In this work, secondary ions outgoing from a patient-like phantom are exploited for the assessment of the lateral pencil beam position in a clinic-like 12C treatment fraction. The experiment was performed at the Heidelberg Ion-Beam Therapy Center (HIT) in Germany. A carbon-ion treatment plan was used to treat a 100 cm3 tumor volume in the center of an Alderson head phantom. Two silicon pixel detectors based on the Timepix3 technology developed at CERN were operated in synchronization to detect and to track outgoing secondary ions. We established an analysis of the measured secondary ion track distribution which enabled us to follow the beam scanning movement of the carbon-ion pencil beam by assessing the lateral position of the single beam spots. The precision of the developed method was found to range from 0.84 mm to 2.59 mm. For beam energies greater than 197.58 MeV/n, the mean of absolute distances of the measured lateral pencil beam positions with respect to the pencil beam positions measured by the beam application system (averaged over each energy layer) were smaller than 2 mm. We conclude that the presented method has shown capabilities of monitoring the lateral pencil beam positions by means of secondary ions with precision and sensitivity of clinical interest.

Dosimetric validation of Monte Carlo and analytical dose engines with raster-scanning 1H, 4He, 12C, and 16O ion-beams using an anthropomorphic phantom

With high-precision radiotherapy on the rise towards mainstream healthcare, comprehensive validation procedures are essential, especially as more sophisticated technologies emerge. In preparation for the upcoming translation of novel ions, case-/disease-specific ion-beam selection and advanced multi-particle treatment modalities at the Heidelberg Ion-beam Therapy Center (HIT), we quantify the accuracy limits in particle therapy treatment planning under complex heterogeneous conditions for the four ions (1H, 4He, 12C, 16O) using a Monte Carlo Treatment Planning platform (MCTP), an independent GPU-accelerated analytical dose engine developed in-house (FRoG) and the clinical treatment planning system (Syngo RT Planning). Attaching an anthropomorphic half-head Alderson RANDO phantom to entrance window of a dosimetric verification water tank, a cubic target spread-out Bragg peak (SOBP) was optimized using the MCTP to best resolve effects of anatomic heterogeneities on dose homogeneity. Subsequent forward calculations were executed in FRoG and Syngo. Absolute and relative dosimetry was performed in the experimental beam room using 1D and 2D array ionization chamber detectors. Mean absolute percent deviation in dose (|%Δ|) between predictions and PinPoint ionization chamber measurements were within ∼2% for all investigated ions for both MCTP and FRoG. For protons and carbon ions, |%Δ| values were ∼4% for Syngo. For the four ions, 3D-γ analysis (3%/3mm criteria) of FLUKA and FRoG presented mean passing rates of 97.0(±2.4)% and 93.6(±4.2)%. FRoG demonstrated satisfactory agreement with gold standard Monte Carlo simulation and measurement, superior to the commercial system. Our pre-clinical trial landmarks the first measurements taken in anthropomorphic settings for helium, carbon and oxygen ion-beam therapy.

Comparison of transcriptional profiles in human lymphocyte cells irradiated with 12C ion beams at 0-2.0 Gy.

ObjectiveHeavy ions have contributed to tumor site-specific radiotherapy and are a major health risk for astronauts. The purpose of this study was to investigate the changes in gene expression in peripheral lymphocytes of cancer patients and astronauts exposed to 12C ions, and identify suitable molecular biomarkers for health monitoring. We also aimed to observe the effects of treatment and the level of damage, by comparing the transcriptional profiles of human lymphocyte cell lines exposed to 12C ion beams at doses of 0–2.0 Gy.Materials and methodsA human lymphocyte cell line was irradiated with 12C ion beams at 0, 0.1, 0.5, and 2.0 Gy and transcriptional profiles were evaluated using the Agilent human gene expression microarray at 24 hours after irradiation. Differentially expressed genes were identified using a fold change of ≥2.0. Representative genes were further validated by RT-PCR. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to determine the roles of differentially expressed mRNAs.ResultsBased on the microarray assays, 1,113 genes were upregulated and 853 genes were downregulated in human lymphocyte cells irradiated with 0.1 Gy 12C ion beams compared with the control group, 1,095 genes were upregulated and 1,220 genes were downregulated in cells irradiated with 0.5 Gy 12C ion beams, and 1,055 genes were upregulated and 1,356 genes were downregulated in cells irradiated with 2.0 Gy. A total of 504 genes were differentially expressed in all irradiated groups, of which 88 genes were upregulated and 416 genes downregulated. Most of these altered genes were related to the cell cycle, apoptosis, signal transduction, DNA transcription, repair, and replication. The expression differences were further confirmed by RT-PCR for a subset of differentially expressed genes.ConclusionDifferentially expressed genes between treatment and control groups at 24 hours post-irradiation increased as the radiation dose increased; upregulated genes gradually decreased and downregulated genes increased. Our data indicated that 12C ion beams could repress a number of genes in a dose-dependent manner, which might lead to the failure of multiple cellular biological functions.

Evaluation of dose distribution of 12C ion beam in radiotherapy by FLUKA as a Monte Carlo simulation Code

Introduction: Nowadays, the use of heavy ion beams in cancer therapy have been developed worldwide. Materials and Methods: It requires accurate understanding of the complex processes of ion interaction with matter, as it is the calculation the relative dose & range of these ions in matter. In the present study we used FLUKA as a numerical Monte Carlo simulations code for simulating the interaction of Carbon Ions beams of potential medical interest with water target as rough models for soft tissue. Results: The depth dose deposition of Carbon ions beam with Energies of 135MeV/u and 195MeV/u in water were simulated and the results were compared with GEANT4 simulation code. Conclusion: The results shows good agreement between FLUKA and GEANT4 and the Experimental data.

Potential lethal damage repair in glioblastoma cells irradiated with ion beams of various types and levels of linear energy transfer.

Glioblastoma (GBM), a Grade IV brain tumour, is a well-known radioresistant cancer. To investigate one of the causes of radioresistance, we studied the capacity for potential lethal damage repair (PLDR) of three altered strains of GBM: T98G, U87 and LN18, irradiated with various ions and various levels of linear energy transfer (LET). The GBM cells were exposed to 12C and 28Si ion beams with LETs of 55, 100 and 200 keV/μm, and with X-ray beams of 1.7 keV/μm. Mono-energetic 12C ions and 28Si ions were generated by the Heavy Ion Medical Accelerator at the National Institute of Radiological Science, Chiba, Japan. Clonogenic assays were used to determine cell inactivation. The ability of the cells to repair potential lethal damage was demonstrated by allowing one identical set of irradiated cells to repair for 24 h before subplating. The results show there is definite PLDR with X-rays, some evidence of PLDR at 55 keV/μm, and minimal PLDR at 100 keV/μm. There is no observable PLDR at 200 keV/μm. This is the first study, to the authors’ knowledge, demonstrating the capability of GBM cells to repair potential lethal damage following charged ion irradiations. It is concluded that a GBM’s PLDR is dependent on LET, dose and GBM strain; and the more radioresistant the cell strain, the greater the PLDR.

L-shell X-ray production cross sections in metal oxide thin films due to 12C, 16O and 28Si ion beams at MeV SIMS energies

Successful co-implementation of different heavy ion beam nuclear analytical techniques such as heavy ion PIXE, ERDA, MeV SIMS and RBS hinges on the availability of accurate databases of fundamental ion beam-matter interaction parameters. We report on measurements carried out to determine L-shell X-ray production cross sections in 101Ru and 181Ta due to 12C, 16O and 28Si projectile ions in the 0.2 MeV/u–1.0 MeV/u energy range. Experimental data is compared to calculations by one of the most widely implemented X-ray ionisation theories in PIXE analyses – the ECPSSR theory in its modified United Atom (UA) version. Results show fairly good agreement between experiment and theory for the 181Ta target atoms, with the level of agreement improving as the Zion/Ztarget ratio decreases and as beam energy increases. For 101Ru target atoms theoretical predictions tend to underestimate experimental data and the discrepancies increase with projectile mass and decreasing energy. The contribution of projectile electron capture (EC) to the measured X-ray production cross sections is also considered in the data analysis and discussion.

Physical parameter optimization scheme for radiobiological studies of charged particle therapy

We have developed an easy-to-implement method to optimize the spatial distribution of a desired physical quantity for charged particle therapy. The basic methodology requires finding the optimal solutions for the weights of the constituent particle beams that together form the desired spatial distribution of the specified physical quantity, e.g., dose or dose-averaged linear energy transfer (LETd), within the target region. We selected proton, 4He ion, and 12C ion beams to demonstrate the feasibility and flexibility of our method. The pristine dose Bragg curves in water for all ion beams and the LETd for proton beams were generated from Geant4 Monte Carlo simulations. The optimization algorithms were implemented using the Python programming language. High-accuracy optimization results of the spatial distribution of the desired physical quantity were then obtained for different cases. The relative difference between the real value and the expected value of a given quantity was approximately within ±1.0% in the whole target region. The optimization examples include a flat dose spread-out Bragg peak (SOBP) for the three selected ions, an upslope dose SOBP for protons, and a downslope dose SOBP for protons. The relative difference was approximately within ±2.0% for the case with a flat LETd (target value = 4 keV/µm) distribution for protons. These one-dimensional optimization algorithms can be extended to two or three dimensions if the corresponding physical data are available. In addition, this physical quantity optimization strategy can be conveniently extended to encompass biological dose optimization if appropriate biophysical models are invoked.

In-field and out-of-file application in 12C ion therapy using fully 3D silicon microdosimeters

This paper presents recent development of Silicon on Insulator (SOI) detectors for microdosimetry at the Centre for Medical Radiation Physics (CMRP) at the University of Wollongong. A new CMRP SOI microdosimeter design, the 3D mushroom microdosimeter is presented. Modification of SOI design and changes to the fabrication processes have led to improved definition of the microscopic sensitive volumes (SV), and thus to better modelling of the deposition of ionizing energy in a biological cell. The electrical and charge collection properties of the devices have been presented in previous works. In this study, the response of the microdosimeters in monoenergetic and spread out Bragg peak therapeutic 12C ion beam at Heavy Ion Medical Accelerator in Chiba (HIMAC, Japan) are presented. Derived relative biological effectiveness (RBE) in 12C ion radiation therapy matches the tissue equivalent proportional counter (TEPC) well, along with outstanding spatial resolution. The use of SOI technology in experimental microdosimetry offers simplicity (no gas system or HV supply), high spatial resolution, low cost, high count rates capabilities for beam characterisation and quality assurance (QA) in charged particle therapy.

Secondary radiation measurements for particle therapy applications: charged particles produced by 4He and 12C ion beams in a PMMA target at large angle

Proton and carbon ion beams are used in the clinical practice for external radiotherapy treatments achieving, for selected indications, promising and superior clinical results with respect to x-ray based radiotherapy. Other ions, like have recently been considered as projectiles in particle therapy centres and might represent a good compromise between the linear energy transfer and the radiobiological effectiveness of ion and proton beams, allowing improved tumour control probability and minimising normal tissue complication probability. All the currently used p, and ion beams allow achieving sharp dose gradients on the boundary of the target volume, however the accurate dose delivery is sensitive to the patient positioning and to anatomical variations with respect to photon therapy. This requires beam range and/or dose release measurement during patient irradiation and therefore the development of dedicated monitoring techniques. All the proposed methods make use of the secondary radiation created by the beam interaction with the patient and, in particular, in the case of ion beams are also able to exploit the significant charged radiation component.Measurements performed to characterise the charged secondary radiation created by and particle therapy beams are reported. Charged secondary yields, energy spectra and emission profiles produced in a poly-methyl methacrylate (PMMA) target by and beams of different therapeutic energies were measured at 60° and 90° with respect to the primary beam direction. The secondary yield of protons produced along the primary beam path in a PMMA target was obtained. The energy spectra of charged secondaries were obtained from time-of-flight information, whereas the emission profiles were reconstructed exploiting tracking detector information. The obtained measurements are in agreement with results reported in the literature and suggests the feasibility of range monitoring based on charged secondary particle detection: the implications for particle therapy monitoring applications are also discussed.

High spatial resolution microdosimetry with monolithic [formula omitted]E-E detector on 12C beam: Monte Carlo simulations and experiment

Nuclear fragmentation produced in 12C ion therapeutic beams contributes significantly to the Relative Biological Effectiveness (RBE)—weighted dose in the distal edge of the Spread out Bragg Peak (SOBP) and surrounding tissues in out-of-field. Complex mixed radiation field originated by the therapeutic 12C ion beam in a phantom is difficult to measure. This study presents a new method to characterise the radiation field produced in a 12C ion beam using a monolithic ΔE-E telescope which provides the capability to identify the particle components of the mixed radiation field as well as the microdosimetric spectra that allows derivation of the RBE based on a radiobiological model. The response of the monolithic ΔE-E telescope to a 290 MeV/u 12C ion beam at defined positions along the pristine Bragg Peak was studied using the Geant4 Monte Carlo toolkit. The microdosimetric spectra derived from the ΔE stage and the two-dimensional scatter plots of energy deposition in ΔE and E stages of the device in coincidence are presented, as calculated in-field and out-of-field. Partial dose weighted contribution to the microdosimetric spectra from nuclear fragments and recoils, such as 1H, 4He, 3He, 7Li, 9Be and 11B, have been analysed for each position. Comparison of simulation and experimental results are presented and demonstrates that the microdosimetric spectra changes dramatically within 0.5 mm depth increments close to and at the distal edge of the Bragg Peak which is impossible to identify using conventional Tissue Equivalent Proportional Counter (TEPC).