12C Ions Research Articles

The Mayo Clinic Florida microdosimetric kinetic model of clonogenic survival: formalism and first benchmark against in vitro and in silico data

Objective. To develop a new model (Mayo Clinic Florida microdosimetric kinetic model, MCF MKM) capable of accurately describing the in vitro clonogenic survival at low and high linear energy transfer (LET) using single-event microdosimetric spectra in a single target. Methodology. The MCF MKM is based on the ‘post-processing average’ implementation of the non-Poisson microdosimetric kinetic model and includes a novel expression to compute the particle-specific quadratic-dependence of the cell survival with respect to dose (β of the linear-quadratic model). A new methodology to a priori calculate the mean radius of the MCF MKM subnuclear domains is also introduced. Lineal energy spectra were simulated with the Particle and Heavy Ion Transport code System (PHITS) for 1H, 4He, 12C, 20Ne, 40Ar, 56Fe, and 132Xe ions and used in combination with the MCF MKM to calculate the ion-specific LET-dependence of the relative biological effectiveness (RBE) for Chinese hamster lung fibroblasts (V79 cell line) and human salivary gland tumor cells (HSG cell line). The results were compared with in vitro data from the Particle Irradiation Data Ensemble (PIDE) and in silico results of different models. The possibility of performing experiment-specific predictions to explain the scatter in the in vitro RBE data was also investigated. Finally, a sensitivity analysis on the model parameters is also included. Main results. The RBE values predicted with the MCF MKM were found to be in good agreement with the in vitro data for all tested conditions. Though all MCF MKM model parameters were determined a priori, the accuracy of the MCF MKM was found to be comparable or superior to that of other models. The model parameters determined a priori were in good agreement with the ones obtained by fitting all available in vitro data. Significance. The MCF MKM will be considered for implementation in cancer radiotherapy treatment planning with accelerated ions.

Measured and GATE predicted PET-image-based activity range verification for carbon therapy: a phantom study

In-beam PET is one of the imaging-based methods for monitoring carbon therapy by reconstruction of positron-emitters produced by incident particles. The accurate Monte Carlo simulation is necessary for range verification and therapeutic dose monitoring by means of the in-beam PET. GATE is capable of performing in-beam PET imaging but very few studies assess the accuracy of activity range measured from PET imaging with GATE simulated results. In this work, we present both experimental and GATE simulation studies of in-beam PET imaging of a phantom, which is irradiated by carbon ion beam, for range verification. The experiment data is acquired at Wuwei Heavy Ion Cancer Treatment Center in Gansu, China, with a dual-head plate PET prototype. The PET prototype consists of 2 panels, each arranged in 2 × 2 matrix. Each detector block is composed of 20 × 20 LYSO crystal array coupled with the position-sensitive photomultiplier tube (HAMAMATSU H8500). A homogeneous plastic phantom is irradiated with monoenergetic 131.05 MeV and 190.19 MeV 12C ion pencil beams. The irradiation and full response of PET prototype are simulated with GATE macros. A novel mathematical model is established, which is capable of calculating and revealing the variation of the positron activity. Our focus is on the reconstructed activity ranges obtained by the experimental measurement and GATE MC prediction combined with the positron activity distribution calculation mathematical model. Results show that the reconstructed activity distribution of experimental data and GATE MC prediction are in good agreement. The measured and simulated 1D activity peak and falling edge positions are within 1.0 mm in all cases. The 20%, 50% and 80% PET peak positions predicted by GATE are close to measurements. These results indicated that it is feasible to assess the accuracy of activity range measured from the dual-head plate PET system with the modeled GATE hadron-PET simulation.

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.

Predicting the Biological Effects of Human Salivary Gland Tumour Cells for Scanned 4He-, 12C-, 16O-, and 20Ne-Ion Beams Using an SOI Microdosimeter

Experimental microdosimetry along with the microdosimetric kinetic (MK) model can be utilized to predict the biological effects of ions. To predict the relative biological effectiveness (RBE) of ions and the survival fraction (SF) of human salivary gland tumour (HSGc-C5) cells, microdosimetric quantities measured by a silicon-on-insulator (SOI) MicroPlus-mushroom microdosimeter along the spread-out Bragg peak (SOBP) delivered by pencil beam scanning of 4He, 12C, 16O, and 20Ne ions were used. The MK model parameters of HSGc-C5 cells were obtained from the best fit of the calculated SF for the different linear energy transfer (LET) of these ions and the formerly reported in vitro SF for the same LET and ions used for calculations. For a cube-shaped target of 10 × 10 × 6 cm3, treatment plans for 4He, 12C, 16O, and 20Ne ions were produced with proprietary treatment planning software (TPS) aiming for 10% SF of HSGc-C5 cells over the target volume and were delivered to a polymethyl methacrylate (PMMA) phantom. Afterwards, the saturation-corrected dose-mean lineal energy derived based on the measured microdosimetry spectra, along with the physical dose at various depths in PMMA phantoms, was used for the estimation of the SF, RBE, and RBE-weighted dose using the MK model. The predicted SF, RBE, and the RBE-weighted dose agreed with what was planned by the TPS within 3% at most depths for these ions.

Selective determination of collectively accelerated 12C ion bunches by neutron time-of-flight spectrometry

In this work, we investigated the possibility of selectively detecting carbon ion bunches collectively accelerated in a Luce diode by a time-of-flight spectrometry of neutrons from the threshold reaction 2H(12C,n)13N induced in Ca(OD)2 layers deposited on Mo substrates by ‘staining’ lime freshly prepared by quenching CaO in heavy water. Oxygen and calcium isotopes do not produce any interference with the analytical reaction on the carbon and proton bunches. This spectrometry confirms that 12C ions and protons are collectively accelerated at the same speed, and 12C ions are captured in this acceleration all the way from the anode to the target, regardless of the conditions of the near-anode plasma.

IDSL.IPA Characterizes the Organic Chemical Space in Untargeted LC/HRMS Data Sets.

Generating comprehensive and high-fidelity metabolomics data matrices from LC/HRMS data remains to be extremely challenging for population-scale large studies (n > 200). Here, we present a new data processing pipeline, the Intrinsic Peak Analysis (IDSL.IPA) R package (https://ipa.idsl.me), to generate such data matrices specifically for organic compounds. The IDSL.IPA pipeline incorporates (1) identifying potential 12C and 13C ion pairs in individual mass spectra; (2) detecting and characterizing chromatographic peaks using a new sensitive and versatile approach to perform mass correction, peak smoothing, baseline development for local noise measurement, and peak quality determination; (3) correcting retention time and cross-referencing peaks from multiple samples by a dynamic retention index marker approach; (4) annotating peaks using a reference database of m/z and retention time; and (5) accelerating data processing using a parallel computation of the peak detection and alignment steps for larger studies. This pipeline has been successfully evaluated for studies ranging from 200 to 1600 samples. By specifically isolating high quality and reliable signals pertaining to carbon-containing compounds in untargeted LC/HRMS data sets from larger studies, IDSL.IPA opens new opportunities for discovering new biological insights in the population-scale metabolomics and exposomics projects. The package is available in the R CRAN repository at https://cran.r-project.org/package=IDSL.IPA.

On the calculation of the relative biological effectiveness of ion radiation therapy using a biological weighting function, the microdosimetric kinetic model (MKM) and subsequent corrections (non-Poisson MKM and modified MKM)

Objective. To investigate similarities and differences in the formalism, processing, and the results of relative biological effectiveness (RBE) calculations with a biological weighting function (BWF), the microdosimetric kinetic model (MKM) and subsequent modifications (non-Poisson MKM, modified MKM). This includes: (a) the extension of the V79-RBE10% BWF to model the RBE for other clonogenic survival levels; (b) a novel implementation of MKMs as weighting functions; (c) a benchmark against Chinese Hamster lung fibroblast (V79) in vitro data; (d) a study on the effect of pre- or post- processing the average biophysical quantities used for the RBE calculations; (e) a possible modification of the modified MKM parameters to improve the model accuracy at high linear energy transfer (LET). Methodology. Lineal energy spectra were simulated for two spherical targets (diameter = 0.464 or 1.0 μm) using PHITS for 1H, 4He, 12C, 20Ne, 40Ar, 56Fe and 132Xe ions. The results of the in silico calculations were compared with published in vitro data. Main results. All models appear to underestimate the RBE α of hydrogen ions. All MKMs generally overestimate the RBE50%, RBE10% and RBE1% for ions with an LET greater than ∼200 keV μm−1. This overestimation is greater for small surviving fractions and is likely due to the assumption of a radiation-independent quadratic term of clonogenic survival (ß). The overall RBE trends seem to be best described by the novel ‘post-processing average’ implementation of the non-Poisson MKM. In case of calculations with the non-Poisson MKM, pre- or post- processing the average biophysical quantities affects the computed RBE values significantly. Significance. This study presents a systematic analysis of the formalism and results of widely used microdosimetric models of clonogenic survival for ions relevant for cancer particle therapy and space radiation protection. Points for improvements were highlighted and will contribute to the development of upgraded biophysical models.

A Data-Driven Fragmentation Model for Carbon Therapy GPU-Accelerated Monte-Carlo Dose Recalculation.

The advent of Graphics Processing Units (GPU) has prompted the development of Monte Carlo (MC) algorithms that can significantly reduce the simulation time with respect to standard MC algorithms based on Central Processing Unit (CPU) hardware. The possibility to evaluate a complete treatment plan within minutes, instead of hours, paves the way for many clinical applications where the time-factor is important. FRED (Fast paRticle thErapy Dose evaluator) is a software that exploits the GPU power to recalculate and optimise ion beam treatment plans. The main goal when developing the FRED physics model was to balance accuracy, calculation time and GPU execution guidelines. Nowadays, FRED is already used as a quality assurance tool in Maastricht and Krakow proton clinical centers and as a research tool in several clinical and research centers across Europe. Lately the core software has been updated including a model of carbon ions interactions with matter. The implementation is phenomenological and based on carbon fragmentation data currently available. The model has been tested against the MC FLUKA software, commonly used in particle therapy, and a good agreement was found. In this paper, the new FRED data-driven model for carbon ion fragmentation will be presented together with the validation tests against the FLUKA MC software. The results will be discussed in the context of FRED clinical applications to 12C ions treatment planning.

Evaluation of the Response of HNSCC Cell Lines to γ-Rays and 12C Ions: Can Radioresistant Tumors Be Identified and Selected for 12C Ion Radiotherapy?

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. Thirty percent of patients will experience locoregional recurrence for which median survival is less than 1 year. Factors contributing to treatment failure include inherent resistance to X-rays and chemotherapy, hypoxia, epithelial to mesenchymal transition, and immune suppression. The unique properties of 12C radiotherapy including enhanced cell killing, a decreased oxygen enhancement ratio, generation of complex DNA damage, and the potential to overcome immune suppression make its application well suited to the treatment of HNSCC. We examined the 12C radioresponse of five HNSCC cell lines, whose surviving fraction at 3.5 Gy ranged from average to resistant when compared with a larger panel of 38 cell lines to determine if 12C irradiation can overcome X-ray radioresistance and to identify biomarkers predictive of 12C radioresponse. Cells were irradiated with 12C using a SOBP with an average LET of 80 keV/μm (CNAO: Pavia, Italy). RBE values varied depending upon endpoint used. A 37 gene signature was able to place cells in their respective radiosensitivity cohort with an accuracy of 86%. Radioresistant cells were characterized by an enrichment of genes associated with radioresistance and survival mechanisms including but not limited to G2/M Checkpoint MTORC1, HIF1α, and PI3K/AKT/MTOR signaling. These data were used in conjunction with an in silico-based modeling approach to evaluate tumor control probability after 12C irradiation that compared clinically used treatment schedules with fixed RBE values vs. the RBEs determined for each cell line. Based on the above analysis, we present the framework of a strategy to utilize biological markers to predict which HNSCC patients would benefit the most from 12C radiotherapy.

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.

MONTE-CARLO SIMULATION USING PHITS OF SECONDARY NEUTRONS PRODUCED IN-PATIENT DURING 16O ION THERAPY.

In hadrontherapy, oxygen ions 16O can be currently considered as an alternative to carbon ions 12C designed specifically for the treatment of deep and radioresistant tumors. Secondary particles, particularly neutrons constitute a serious problem of undesirable additional irradiation to surrounding healthy tissue. The objective of this study is to evaluate, by Monte-Carlo simulation [code Particle and Heavy Ion Transport code System (PHITS)], the contribution in terms of dose of secondary neutrons produced during interaction 16O ion of 300MeV u-1 in a soft tissue phantom. The dose of 16O ion, secondary particles and neutrons is evaluated, as well as the particle fluence and energy spectra of neutrons. The contribution to the total dose of secondary neutrons in a soft tissue phantom represents 0.1%. This dose, although apparently insignificant, is essential to conduct even more in-depth studies to understand the long-term effects of these secondary neutrons on the patient's body especially in pediatric case.

Theoretical and experimental estimation of the relative optically stimulated luminescence efficiency of an optical-fiber-based BaFBr:Eu detector for swift ions

ABSTRACT The reliability of dose assessment with radiation detectors is an important feature in various fields, such as radiotherapy, radiation protection, and high-energy physics. However, many detectors irradiated by high linear energy transfer (LET) radiations exhibit decreased efficiency called the quenching effect. This quenching effect depends not only on the particle LET but also strongly on the ion species and its microscopic pattern of energy deposition. Recently, a computational method for estimating the relative efficiency of luminescence detectors has been proposed following the analysis of microdosimetric specific energy distributions simulated using the particle and heavy ion transport code system (PHITS). This study applied the model to estimate the relative optically stimulated luminescence (OSL) efficiency of BaFBr:Eu detectors. Additionally, we measured the luminescence intensity of BaFBr:Eu detectors exposed to 4He, 12C, and 20Ne ions to verify the calculated data. The model reproduced the experimental data in the cases of adopting a microdosimetric target diameter of approximately 30–50 nm. The calculated relative efficiency exhibits ion-species dependence in addition to LET. This result shows that the microdosimetric calculation from specific energy is a successful method for accurately understanding the results of OSL measurements with BaFBr:Eu detectors irradiated by various particles.

Image reconstruction from a large number of projections in proton and 12C ions computed tomography using sequential and parallel ART algorithms

The Algebraic Reconstruction Technique (ART) algorithm plays an important role in image reconstruction in Computed Tomography in Medical Radiology—a branch of medicine that uses imaging technology to diagnose and treat disease. This study implements two types of ART algorithms: sequential and parallel, to speed up image reconstruction with a higher number of projections. ART Algorithms used the available HP Proliant D2 585 G7 with 64-cores and a shared memory environment that used OpenMP. These algorithms were applied iteratively for each of the 72 projections, 180 projections, and 360 projections. The parallel implementation of the ART algorithm was evaluated at an average of 42% faster in all projections as compared with the sequential ART algorithm. The ART algorithm was implemented in parallel and was faster compared to the sequential ART algorithm which is essential in Medical Radiology in the speeding up of image reconstruction.

The Use of ProteoTuner Technology to Study Nuclear Factor κB Activation by Heavy Ions.

Nuclear factor κB (NF-κB) activation might be central to heavy ion-induced detrimental processes such as cancer promotion and progression and sustained inflammatory responses. A sensitive detection system is crucial to better understand its involvement in these processes. Therefore, a DD-tdTomato fluorescent protein-based reporter system was previously constructed with human embryonic kidney (HEK) cells expressing DD-tdTomato as a reporter under the control of a promoter containing NF-κB binding sites (HEK-pNFκB-DD-tdTomato-C8). Using this reporter cell line, NF-κB activation after exposure to different energetic heavy ions (16O, 95 MeV/n, linear energy transfer—LET 51 keV/µm; 12C, 95 MeV/n, LET 73 keV/μm; 36Ar, 95 MeV/n, LET 272 keV/µm) was quantified considering the dose and number of heavy ions hits per cell nucleus that double NF-κB-dependent DD-tdTomato expression. Approximately 44 hits of 16O ions and ≈45 hits of 12C ions per cell nucleus were required to double the NF-κB-dependent DD-tdTomato expression, whereas only ≈3 hits of 36Ar ions were sufficient. In the presence of Shield-1, a synthetic molecule that stabilizes DD-tdTomato, even a single particle hit of 36Ar ions doubled NF-κB-dependent DD-tdTomato expression. In conclusion, stabilization of the reporter protein can increase the sensitivity for NF-κB activation detection by a factor of three, allowing the detection of single particle hits’ effects.

Quantitative modeling of carcinogenesis induced by single beams or mixtures of space radiations using targeted and non-targeted effects

Ionizing radiations encountered by astronauts on deep space missions produce biological damage by two main mechanisms: (1) Targeted effects (TE) due to direct traversals of cells by ionizing tracks. (2) Non-targeted effects (NTE) caused by release of signals from directly hit cells. The combination of these mechanisms generates non-linear dose response shapes, which need to be modeled quantitatively to predict health risks from space exploration. Here we used a TE + NTE model to analyze data on APC(1638N/+) mouse tumorigenesis induced by space-relevant doses of protons, 4He, 12C, 16O, 28Si or 56Fe ions, or γ rays. A customized weighted Negative Binomial distribution was used to describe the radiation type- and dose-dependent data variability. This approach allowed detailed quantification of dose–response shapes, NTE- and TE-related model parameters, and radiation quality metrics (relative biological effectiveness, RBE, and radiation effects ratio, RER, relative to γ rays) for each radiation type. Based on the modeled responses for each radiation type, we predicted the tumor yield for a Mars-mission-relevant mixture of these radiations, using the recently-developed incremental effect additivity (IEA) synergy theory. The proposed modeling approach can enhance current knowledge about quantification of space radiation quality effects, dose response shapes, and ultimately the health risks for astronauts.

Ultra-High Dose Rate (FLASH) Carbon Ion Irradiation: Dosimetry and First Cell Experiments

To establish a beam monitoring and dosimetry system to enable the FLASH dose rate carbon ion irradiation and investigate, at different oxygen concentrations, the in vitro biological response in comparison to the conventional dose rate. CHO-K1 cell response to irradiation at different dose rates and at different levels of oxygenation was studied using clonogenic assay. The Heidelberg Ion-Beam Therapy Center (HIT) synchrotron, after technical improvements, was adjusted to extract ≥5×108 12C ions within approximately 150 milliseconds. The beam monitors were filled with helium. The FLASH irradiation with beam scanning yields a dose of 7.5 Gy (homogeneity of ±5%) for a 280 MeV/u beam in a volume of at least 8 mm in diameter and a corresponding dose rate of 70 Gy/s (±20%). The dose repetition accuracy is better than 2%, the systematic uncertainty is better than 2%. Clonogenic assay demonstrates a significant FLASH sparing effect which is strongly oxygenation-dependent and mostly pronounced at 0.5% O2 but absent at 0% and 21% O2. The FLASH dose rates >40 Gy/s were achieved with carbon beams. Cell survival analysis revealed FLASH dose rate sparing in hypoxia (0.5%-4% O2).

Long-Term Persistence of Increased Number of γH2AX+ Peripheral Blood Lymphocytes in Monkeys Exposed to Negative Factors of Space Flights: Ionizing Radiation and Simulated Hypogravity.

We studied the influence of ionizing radiation and hypogravity as negative factors of space flights on DNA damage in peripheral blood lymphocytes of rhesus monkeys at different times after exposure (from 1 to 446 days). The proportion of cells with high numbers of DNA double-strand breaks (DSB), positive for the surrogate DSB marker-protein γH2AX, was monitored using flow cytometry. Some animals were exposed to 7-day antiorthostatic hypokinesia simulating hypogravity, the others to a combined effect of antiorthostatic hypokinesia, whole-body γ-irradiation (2.34 cGy/h, dose 1 Gy), and irradiation of the head with 12C ions (450 MeV, dose 1 Gy). Exposure to antiorthostatic hypokinesia led to a significant increase in the proportion of γH2AX+ lymphocytes only on the first day after exposure, whereas after combined exposure, increased numbers of damaged lymphocytes were recorded up to 42 days after exposure.

High-energy per-pixel calibration of timepix pixel detector with laboratory alpha source

The spectral response of the pixel detector Timepix at the high per-pixel proportional range is examined and calibrated using a simple technique and alpha particles from a standard laboratory source in air. For the detector used, a Timepix ASIC chip equipped with a 300 μ m thick silicon sensor, the spectral range is newly extended up to about 1750 keV per-pixel. This expands and covers the region above 850 keV per pixel which is described and covered by the existing low-energy calibration. The low-energy calibration uses discrete low-energy gamma rays in the range 5–60 keV and is extrapolated over the linear range up to 850 keV/px. Above this level, the per-pixel spectral response changes. At higher energies it undergoes distortion and saturation. The proportional and monotonic response is observed with regions of varying dependence up to nearly 2 MeV. This high-energy region is covered and described by the newly developed calibration method which Uses an alpha source of common low activity (kBq level). Data are collected within one day of total measuring time. Measurements are performed in air at various source-to-distance positions and several sensor bias settings. The developed method together with suitable setting of the sensor bias, which determines the extent of charge sharing, expands the spectral response of Timepix to high energy-loss particles such as alpha particles and light ions in wide energy range. Results are demonstrated on alpha particles, protons and 12C ions. Resulting spectra of deposited energy and cluster pixel height are correctly calibrated and they reproduce expected values.

Interaction of therapeutic 12C ions with bone-like targets: physical characterization and dosimetric effect at material interfaces

Carbon therapy is a promising treatment option for cancer. The physical and biological properties of carbon ions can theoretically allow for the delivery of curative doses to the tumor, while simultaneously limiting risks of toxicity to adjacent healthy structures. The treatment effectiveness can be further improved by decreasing the uncertainties stemming from several sources, including the modeling of tissue heterogeneity. Current treatment plans employ density-based conversion methods to translate patient-specific anatomy into a water system, where dose distribution is calculated. This approach neglects differences in nuclear interactions stemming from the elemental composition of each tissue. In this work, we investigated the interaction of therapeutic carbon ions with bone-like materials. The study concentrated on nuclear interactions and included attenuation curves of 200 and 400 AMeV beams in different types of bones, as well as kinetic energy spectra of all charged fragments produced up to 29 degrees from the beam direction. The comparison between measurements and calculations of the treatment planning system TRiP98 indicated that bone tissue causes less fragmentation of carbon ions than water. Overall, hydrogen and helium particles were found to be the most abundant species, while heavier fragments were mostly detected within 5 degrees from the beam direction. We also investigated how the presence of a soft tissue-bone interface could affect the depth-dose profile. The results revealed a dose spike in the transition region, that extended from the entry channel to the target volume. The findings of this work indicated that the tissue-to-water conversion method based only on density considerations can result in dose inaccuracies. Tissue heterogeneity regions containing bones can potentially produce dose spikes, whose magnitude will depend on the patient anatomy. Dose uncertainties can be decreased by modeling nuclear interactions directly in bones, without applying the tissue-to-water conversion.