Fano cavity test and investigation of the response of the Roos chamber irradiated by proton beams in perpendicular magnetic fields up to 1 T.

Objective. The aim of this work is to investigate the response of the Roos chamber (type 34001) irradiated by clinical proton beams in magnetic fields.Approach. At first, a Fano test was implemented in Monte Carlo software package GATE version 9.2 (based on Geant4 version 11.0.2) using a cylindrical slab geometry in a magnetic field up to 1 T. In accordance to an experimental setup (Fuchset al2021), the magnetic field correction factorskQB⃗of the Roos chamber were determined at different energies up to 252 MeV and magnetic field strengths up to 1 T, by separately simulating the ratios of chamber signalsMQ/MQB⃗,without and with magnetic field, and the dose-conversion factorsDw,QB⃗/Dw,Qin a small cylinder of water, with and without magnetic field. Additionally, detailed simulations were carried out to understand the observed magnetic field dependence.Main results. The Fano test was passed with deviations smaller than 0.25% between 0 and 1 T. The ratios of the chamber signals show both energy and magnetic field dependence. The maximum deviation of the dose-conversion factors from unity of 0.22% was observed at the lowest investigated proton energy of 97.4 MeV andB⃗= 1 T. The resultingkQB⃗factors increase initially with the applied magnetic field and decrease again after reaching a maximum at around 0.5 T; except for the lowest 97.4 MeV beam that show no observable magnetic field dependence. The deviation from unity of the factors is also larger for higher proton energies, where the maximum lies at 1.0035(5), 1.0054(7) and 1.0069(7) for initial energies ofE0= 152, 223.4 and 252 MeV, respectively.Significance. Detailed Monte Carlo studies showed that the observed effect can be mainly attributed to the differences in the transport of electrons produced both outside and inside of the air cavity in the presence of a magnetic field.

Radiobiological Assessment of Targeted Radionuclide Therapy with [177Lu]Lu-PSMA-I&T in 2D vs. 3D Cell Culture Models.

In vitro therapeutic efficacy studies are commonly conducted in cell monolayers. However, three-dimensional (3D) tumor spheroids are known to better represent in vivo tumors. This study used [177Lu]Lu-PSMA-I&T, an already clinically applied radiopharmaceutical for targeted radionuclide therapy against metastatic castrate-resistant prostate cancer, to demonstrate the differences in the radiobiological response between 2D and 3D cell culture models of the prostate cancer cell lines PC-3 (PSMA negative) and LNCaP (PSMA positive). After assessing the target expression in both models via Western Blot, cell viability, reproductive ability, and growth inhibition were assessed. To investigate the geometric effects on dosimetry for the 2D vs. 3D models, Monte Carlo simulations were performed. Our results showed that PSMA expression in LNCaP spheroids was highly preserved, and target specificity was shown in both models. In monolayers of LNCaP, no short-term (48 h after treatment), but only long-term (14 days after treatment) radiobiological effects were evident, showing decreased viability and reproductive ability with the increasing activity. Further, LNCaP spheroid growth was inhibited with the increasing activity. Overall, treatment efficacy was higher in LNCaP spheroids compared to monolayers, which can be explained by the difference in the resulting dose, among others.

MR-guided ion therapy: Detector response in magnetic fields during carbon ion irradiation.

BACKGROUND: Combining carbon ion therapy with on-bed MR imaging has the potential to bring particle therapy to a new level of precision. However, the introduction of magnetic fields brings challenges for dosimetry and quality assurance. For protons, a small, but significant change in detector response was shown in the presence of magnetic fields previously. For carbon ion beams, so far no such experiments have been performed. PURPOSE: To investigate the influence of external magnetic fields on the response of air-filled ionization chambers. METHODS: Four commercially available ionization chambers, three thimble type (Farmer, Semiflex, and PinPoint), and a plane parallel (Bragg peak) detector were investigated. Detectors were aligned in water such that their effective point of measurement was located at 2 cm depth. Irradiations were performed using 10 × 10 cm 2 $10\times 10\nobreakspace \mathrm{cm}^2$ square fields for carbon ions of 186.1, 272.5, and 402.8 MeV/u employing magnetic field strengths of 0, 0.25, 0.5, and 1 T. In addition, the detector response for protons and carbon ions was compared taking into account the secondary electron spectra and employing protons of 252.7 MeV for comparison. RESULTS: For all four detectors, a statistically significant change in detector response, dependent on the magnetic field strength, was found. The effect was more pronounced for higher energies. The highest effects were found at 0.5 T for the PinPoint detector with a change in detector response of 1.1%. The response of different detector types appeared to be related to the cavity diameter. For proton and carbon ion irradiation with similar secondary electron spectra, the change in detector response was larger for carbon ions compared to protons. CONCLUSION: A small, but significant dependence of the detector response was found for carbon ion irradiation in a magnetic field. The effect was found to be larger for smaller cavity diameters and at medium magnetic field strengths. Changes in detector response were more pronounced for carbon ions compared to protons.

Efficient full Monte Carlo modelling and multi-energy generative model development of an advanced X-ray device.

Monte Carlo (MC) simulations of X-ray image devices require splitting the simulation into two parts (i.e. the generation of x-rays and the actual imaging). The X-ray production remains unchanged for repeated imaging and can thus be stored in phase space (PhS) files and used for subsequent MC simulations. Especially for medical images these dedicated PhS files require a large amount of data storage, which is partly why Generative Adversarial Networks (GANs) were recently introduced. We enhanced the approach by a conditional GAN to model multiple energies using one network. This study compares the use of PhSs, GANs, and conditional GANs as photon source with measurements. An X-ray -based imaging system (i.e. ImagingRing) was modelled in this study. half-value layers (HVLs), focal spot, and Heel effect were measured for subsequent comparison. MC simulations were performed with GATE-RTion v1.0 considering the geometry and materials of the imaging system with vendor specific schematics. A traditional GAN model as well as the favourable conditional GAN was implemented for PhS generation. Results of the MC simulation were in agreement with the measurements regarding HVL, focal spot, and Heel effect. The conditional GAN performed best with a non-saturated loss function with R1 regularisation and gave similarly results as the traditional GAN approach. GANs proved to be superior to the PhS approach in terms of data storage and calculation overhead. Moreover, a conditional GAN enabled an energy interpolation to separate the network training process from the final required X-ray energies.

Commissioning a beam line for MR-guided particle therapy assisted by in silico methods.

BACKGROUND: Radiation therapy is continuously moving towards more precise dose delivery. The combination of online MR imaging and particle therapy, for example, radiation therapy using protons or carbon ions, could enable the next level of precision in radiotherapy. In particle therapy, research towards a combination of MR and particle therapy is well underway, but still far from clinical systems. The combination of high magnetic fields with particle therapy delivery poses several challenges for treatment planning, treatment workflow, dose delivery, and dosimetry. PURPOSE: To present a workflow for commissioning of a light ion beam line with an integrated dipole magnet to perform MR-guided particle therapy (MRgPT) research, producing not only basic beam data but also magnetic field maps for accurate dose calculation. Accurate dose calculation in magnetic field environments requires high-quality magnetic field maps to compensate for magnetic-field-dependent trajectory changes and dose perturbations. METHODS: The research beam line at MedAustron was coupled with a resistive dipole magnet positioned at the isocenter. Beam data were measured for proton and carbon ions with and without an applied magnetic field of 1 T. Laterally integrated depth-dose curves (IDC) as well as beam profiles were measured in water while beam trajectories were measured in air. Based on manufacturer data, an in silico model of the magnet was created, allowing to extract high-quality 3D magnetic field data. An existing GATE/Geant4 Monte Carlo (MC) model of the beam line was extended with the generated magnetic field data and benchmarked against experimental data. RESULTS: A 3D magnetic field volume covering fringe fields until 50 mT was found to be sufficient for an accurate beam trajectory modeling. The effect on particle range retraction was found to be 2.3 and 0.3 mm for protons and carbon ions, respectively. Measured lateral beam offsets in water agreed within 0.4 and -0.5 mm with MC simulations for protons and carbon ions, respectively. Experimentally determined in-air beam trajectories agreed within 0.4 mm in the homogeneous magnetic field area. CONCLUSION: The presented approach based on in silico modeling and measurements allows to commission a beam line for MRgPT while providing benchmarking data for the magnetic field modeling, required for state-of-the art dose calculation methods.

The OpenGATE ecosystem for Monte Carlo simulation in medical physics.

This paper reviews the ecosystem of GATE, an open-source Monte Carlo toolkit for medical physics. Based on the shoulders of Geant4, the principal modules (geometry, physics, scorers) are described with brief descriptions of some key concepts (Volume, Actors, Digitizer). The main source code repositories are detailed together with the automated compilation and tests processes (Continuous Integration). We then described how the OpenGATE collaboration managed the collaborative development of about one hundred developers during almost 20 years. The impact of GATE on medical physics and cancer research is then summarized, and examples of a few key applications are given. Finally, future development perspectives are indicated.

An external perpendicular magnetic field does not influence survival and DNA damage after proton and carbon ion irradiation in human cancer cells.

BACKGROUND AND PURPOSE: Magnetic field effects on the radiobiological effectiveness during treatment of magnetic resonance (MRI) guided particle therapy are being debated. This study aims at assessing the influence of a perpendicular magnetic field on the biological effects in two human cancer cell lines irradiated with proton or carbon ions. METHODS AND MATERIALS: In vitro cell irradiations were performed in water inside a perpendicular magnetic field of 0 and 1T for both protons and carbon ions. Samples were located in the center of a spread-out Bragg peak at 8cm water equivalent depth with a dose averaged linear energy transfer (LETd) of 4.2 or 83.4keV/µm for protons and carbon ions, respectively. Physical dose levels of 0, 0.5, 1, 2, 4 and 6Gy were employed. The irradiation field was shifted and laterally enlarged, to compensate for the beam deflection due to the magnetic field and ensure consistent and homogenous irradiations of the flasks. The human cancer cell lines SKMel (Melanoma) and SW1353 (chondrosarcoma) were selected which represent a high and a low (α/ß)x ratio cell type. Cell survival curves were generated applying a linear-quadratic curve fit. DNA damage and DNA damage clearance were assessed via γH2AX foci quantification at 1 and 24h post radiation treatment. RESULTS: Without a magnetic field, RBE10 values of 1.04±0.03 (SW1353) and 1.51±0.06 (SKMel) as well as RBE80 values of 0.93±0.15 (SW1353) and 2.28±0.40 (SKMel) were calculated for protons. Carbon treatments yielded RBE10 values of 1.68±0.04 (SW1353) and 2.30±0.07 (SKMel) and RBE80 values of 2.19±0.24 (SW1353) and 4.06±0.33 (SKMel). For a field strength of B=1T, RBE10 values of 1.06±0.03 (SW1353) and 1.47±0.06 (SKMel) resulted from protons, while RBE10 values of 1.70±0.05 (SW1353) and 2.37±0.08 (SKMel) were obtained for carbon ions. RBE80 values were calculated to be 1.06±0.12 (SW1353) and 2.33±0.40 (SKMel) following protons and 2.13±0.25 (SW1353) and 4.29±0.35 (SKMel) following carbon treatments. Substantially increased γH2AX foci per nucleus were found in both cell lines 1h after radiation with both ion species. At the 24h time point only carbon treated samples of both cell lines showed increased γH2AX levels. The presence of the magnetic field did neither influence the survival parameters of either cell line, nor initial DNA damage and DNA damage clearance. CONCLUSIONS: Applying a perpendicular magnetic field did not influence the cell survival, DNA repair, nor the biological effectiveness of protons or carbon ions in two human cancer cell lines.

Computer-assisted beam modeling for particle therapy.

PURPOSE: To develop a computer-driven and thus less user-dependent method, allowing for a simple and straightforward generation of a Monte Carlo (MC) beam model of a scanned proton and carbon ion beam delivery system. METHODS: In a first step, experimental measurements were performed for proton and carbon ion energies in the available energy ranges. Data included depth dose profiles measured in water and spot sizes in air at various isocenter distances. Using an automated regularization-based optimization process (AUTO-BEAM), GATE/Geant4 beam models of the respective beam lines were generated. These were obtained sequentially by using least square weighting functions with and without regularization, to iteratively tune the beam parameters energy, energy spread, beam sigma, divergence, and emittance until a user-defined agreement was reached. Based on the parameter tuning for a set of energies, a beam model was semi-automatically generated. The resulting beam models were validated for all centers comparing to independent measurements of laterally integrated depth dose curves and spot sizes in air. For one representative center, three-dimensional dose cubes were measured and compared to simulations. The method was applied on one research as well as four different clinical beam lines for proton and carbon ions of three different particle therapy centers using synchrotron or cyclotron accelerator systems: (a) MedAustron ion therapy center, (b) University Proton Therapy Dresden, and (c) Center Antoine Lacassagne Nice. RESULTS: Particle beam ranges in the MC beam models agreed on average within 0.2 mm compared to measurements for all energies and beam lines. Spot sizes in air (full-width at half maximum) at all positions differed by less than 0.4% from the measurements. Dose calculation with the beam model for the clinical beam line at MedAustron agreed better than 1.7% in absolute dose for a representative clinical case treated with protons. For protons, beam model generation, including geometry creation, data conversion, and validation, was possible within three working days. The number of iterations required for the optimization process to converge, was found to be similar for all beam line geometries and particle types. CONCLUSION: The presented method was demonstrated to work independently of the beam optics behavior of the different beam lines, particle types, and geometries. Furthermore, it is suitable for non-expert users and requires only limited user interaction. Beam model validation for different beam lines based on different beam delivery systems, showed good agreement.

Technical Note: Design and commissioning of a water phantom for proton dosimetry in magnetic fields.

PURPOSE: To design and commission a water phantom suitable for constrained environments and magnetic fields for magnetic resonance (MR)-guided proton therapy. METHODS: A phantom was designed, to enable precise, remote controlled detector positioning in water within the constrained environment of a magnet for MR-guided proton therapy. The phantom consists of a PMMA enclosure whose outer dimensions of 81 × 40 × 12.5 cm 3 were chosen to optimize space usage inside the 13.5-cm bore gap of the magnet. The moving mechanism is based on a low-height H-shaped non-ferromagnetic belt drive, driven by stepper motors located outside of the magnetic field. The control system and the associated electronics were designed in house, with similar features as available in commercial water phantoms. Reproducibility as well as accuracy of the phantom positioning were tested using a high-precision Leica AT 402 laser tracker. Laterally integrated depth dose curves and lateral beam profiles at three depths were acquired repeatedly for a 148.2 MeV proton beam in water. RESULTS: The phantom was successfully operated with and without applied magnetic fields. For complex movements, a positioning uncertainty within 0.16 mm was found with an absolute accuracy typically below 0.3 mm. Laterally integrated depth dose curves agreed within 0.1 mm with data taken using a commercial water phantom. The lateral beam offset determined from beam profile measurements agreed well with data from Monte Carlo simulations. CONCLUSION: The phantom is optimally suited for detector positioning and dosimetric experiments within constrained environments in high magnetic fields.

The practical radius of a pencil beam in proton therapy.

The central Gaussian shaped high dose region of a pencil beam (PB) in light ion beam therapy (LIBT) is enveloped by a low dose region causing non-negligible field size effects and impairs the dose calculation accuracy considerably if the low dose envelope is not well modeled. The purpose of this study was to calculate the practical radius, Rc, at which a PB does not influence a field more than a certain accuracy level. Lateral dose profiles of proton beams in water were simulated using GATE/Geant4. Those lateral dose profiles were integrated numerically and used to calculate field size factors (FSFs). The Rc was then determined such, that the lateral dose at radii exceeding Rc can be neglected without compromising the FSF of a 20cm×20cm field more than a desired accuracy level c. The practical radius Rc yielding c=0.5% was compared to the frequently applied concept of full width at a ratio x of the maximum (FWxM). The sensitivity to variations of the beam width was tested by increasing the initial beam width σC of the clinical beam model by 0.5 and 1mm, respectively. Neglecting the dose at radii exceeding Rc resulted in the desired FSF accuracy, whereas using the FW0.01%M cut resulted in varying accuracy. In order to yield a constant FSF accuracy, the ratio x in FWxM ranged from 0.003% to 0.065% of the maximum. In contrast to Rc, FWxM was sensitive to variations of the initial beam width. The maximum Rc over all depths was less than 7cm for the low(62.4MeV) and medium(148.2MeV) proton energy beam, which suggests that a plane parallel ionization chamber exceeding that radius is sufficient to acquire laterally integrated depth dose distributions for those energies. However, this holds not true for the highest energy (252.7MeV) or when including a range shifter (RaShi). The values of Rc are specific to our beam line configuration as the maximum Rc was depending on both, the scattering material in the Nozzle as well as the distance of the air-gap between Nozzle and phantom.

Experimental benchmarking of RayStation proton dose calculation algorithms inside and outside the target region in heterogeneous phantom geometries.

PURPOSE: The aim of the presented study was to complement existing literature on benchmarking proton dose by comparing dose calculations with experimental measurements in heterogeneous phantom. Points of interest inside and outside the target were considered to quantify the magnitude of calculation uncertainties in current and previous proton therapy practice that might especially have an impact on the dose in organs at risk (OARs). METHODS: The RayStation treatment planning system (RaySearch Laboratories), offering two dose calculation algorithms for pencil beam scanning in proton therapy, i.e., Pencil Beam (PB) and Monte Carlo (MC), was utilized. Treatment plans for a target located behind the interface of the heterogeneous tissues were generated. Dose measurements within and behind the target were performed in a water phantom with embedded slabs of various tissue equivalent materials and 24 PinPoint ionization chambers (PTW). In total 12 test configurations encompassing two different target depths, oblique beam incidence of 30 degrees and range shifter, were considered. RESULTS: PB and MC calculated doses agreed equally well with the measurements for all test geometries within the target, including the range shifter (mean dose differences ± 3%). Outside the target, the maximum dose difference of 9% (19%) was observed for MC (PB) for the oblique beam incidence and inserted range shifter. CONCLUSION: The accuracy of MC dose algorithm was superior compared to the PB algorithm, especially outside the target volumes. MC based dose calculation should therefore be preferred in treatment scenarios with heterogeneities, especially to reduce clinically relevant uncertainties for OARs.

Implementation of a dose calculation algorithm based on Monte Carlo simulations for treatment planning towards MRI guided ion beam therapy.

Magnetic resonance guidance in particle therapy has the potential to improve the current performance of clinical workflows. However, the presence of magnetic fields challenges the current algorithms for treatment planning. To ensure proper dose calculations, compensation methods are required to guarantee that the maximum deposited energy of deflected beams lies in the target volume. In addition, proper modifications of the intrinsic dose calculation engines, accounting for magnetic fields, are needed. In this work, an algorithm for proton treatment planning in magnetic fields was implemented in a research treatment planning system (TPS), matRad. Setup-specific look up tables were generated using a validated MC model for a clinical proton beamline (62.4 - 215.7 MeV) interacting with a dipole magnet (B = 0-1 T). The algorithm was successfully benchmarked against MC simulations in water, showing gamma index (2%/2mm) global pass rates higher than 96% for different plan configurations. Additionally, absorbed depth doses were compared with experimental measurements in water. Differences within 2% and 3.5% in the Bragg peak and entrance regions, respectively, were found. Finally, treatment plans were generated and optimized for magnetic field strengths of 0 and 1 T to assess the performance of the proposed model. Equivalent treatment plans and dose volume histograms were achieved, independently of the magnetic field strength. Differences lower than 1.5% for plan quality indicators (D2%, D50%, D90%, V95% and V105%) in water, a TG119 phantom and an exemplary prostate patient case were obtained. More complex treatment planning studies are foreseen to establish the limits of applicability of the proposed model.

Characterization of the PTW-34089 type 147 mm diameter large-area ionization chamber for use in light-ion beams.

A newly-designed large-area plane-parallel ionization chamber (of type PTW 34089), denoted BPC150, with a nominal active volume diameter of 147 mm is characterized in this study. Such chambers exhibit benefits compared to smaller chambers in the field of scanned light-ion beam dosimetry because they capture a larger fraction of the laterally-spread beam fragments and ease positioning with respect to small fields. The chamber was characterized in 60Co, 200 kV x-ray, proton and carbon ion beams. The chamber-specific beam-quality correction factor kQ,Q0 was determined. To investigate the homogeneity of the chamber's response, a radial response map was acquired. An edge correction was applied when the proton beam only partly impinged on the chamber's active surface. The measured response map showed that the response in the chamber's center is 3% lower than the average response over the total active area. Furthermore, percentage depth dose (PDD) curves in carbon ions were acquired and compared to those obtained with smaller-diameter chambers (i.e. 81.6 mm and 39.6 mm) as well as with results from Monte Carlo simulations. The measured absorbed dose to water cross calibration coefficients resulted in a kQ,Q0 of 0.981 ± 0.020. Regarding carbon ion PDD curves, relative differences between the BPC150 and smaller chambers were observed, especially for higher energies and in the fragmentation tail. These differences reached 10%-22% in the fragmentation tail (compared to the 81.6 mm diameter chamber). Differences increased when comparing to a chamber with 39.6 mm diameter. The provided results characterize the BPC150 thoroughly for usage in scanned light-ion beam dosimetry and demonstrate its advantage of capturing a larger fraction of the laterally-integrated dose in the fragmentation tail.

A GATE/Geant4 beam model for the MedAustron non-isocentric proton treatment plans quality assurance.

PURPOSE: To present a reference Monte Carlo (MC) beam model developed in GATE/Geant4 for the MedAustron fixed beam line. The proposed model includes an absolute dose calibration in Dose-Area-Product (DAP) and it has been validated within clinical tolerances for non-isocentric treatments as routinely performed at MedAustron. MATERIAL AND METHODS: The proton beam model was parametrized at the nozzle entrance considering optic and energy properties of the pencil beam. The calibration in terms of absorbed dose to water was performed exploiting the relationship between number of particles and DAP by mean of a recent formalism. Typical longitudinal dose distribution parameters (range, distal penumbra and modulation) and transverse dose distribution parameters (spot sizes, field sizes and lateral penumbra) were evaluated. The model was validated in water, considering regular-shaped dose distribution as well as clinical plans delivered in non-isocentric conditions. RESULTS: Simulated parameters agree with measurements within the clinical requirements at different air gaps. The agreement of distal and longitudinal dose distribution parameters is mostly better than 1 mm. The dose difference in reference conditions and for 3D dose delivery in water is within 0.5% and 1.2%, respectively. Clinical plans were reproduced within 3%. CONCLUSION: A full nozzle beam model for active scanning proton pencil beam is described using GATE/Geant4. Absolute dose calibration based on DAP formalism was implemented. The beam model is fully validated in water over a wide range of clinical scenarios and will be inserted as a reference tool for research and for independent dose calculation in the clinical routine.

Benchmarking a GATE/Geant4 Monte Carlo model for proton beams in magnetic fields.

PURPOSE: Magnetic resonance guidance in proton therapy (MRPT) is expected to improve its current performance. The combination of magnetic fields with clinical proton beam lines poses several challenges for dosimetry, treatment planning and dose delivery. Proton beams are deflected by magnetic fields causing considerable changes in beam trajectories and also a retraction of the Bragg peak positions. A proper prediction and compensation of these effects is essential to ensure accurate dose calculations. This work aims to develop and benchmark a Monte Carlo (MC) beam model for dose calculation of MRPT for static magnetic fields up to 1 T. METHODS: Proton beam interactions with magnetic fields were simulated using the GATE/Geant4 toolkit. The transport of charged particle in custom 3D magnetic field maps was implemented for the first time in GATE. Validation experiments were done using a horizontal proton pencil beam scanning system with energies between 62.4 and 252.7 MeV and a large gap dipole magnet (B = 0-1 T), positioned at the isocenter and creating magnetic fields transverse to the beam direction. Dose was measured with Gafchromic EBT3 films within a homogeneous PMMA phantom without and with bone and tissue equivalent material slab inserts. Linear energy transfer (LET) quenching of EBT3 films was corrected using a linear model on dose-averaged LET method to ensure a realistic dosimetric comparison between simulations and experiments. Planar dose distributions were measured with the films in two different configurations: parallel and transverse to the beam direction using single energy fields and spread-out Bragg peaks. The MC model was benchmarked against lateral deflections and spot sizes in air of single beams measured with a Lynx PT detector, as well as dose distributions using EBT3 films. Experimental and calculated dose distributions were compared to test the accuracy of the model. RESULTS: Measured proton beam deflections in air at distances of 465, 665, and 1155 mm behind the isocenter after passing the magnetic field region agreed with MC-predicted values within 4 mm. Differences between calculated and measured beam full width at half maximum (FWHM) were lower than 2 mm. For the homogeneous phantom, measured and simulated in-depth dose profiles showed range and average dose differences below 0.2 mm and 1.2%, respectively. Simulated central beam positions and widths differed <1 mm to the measurements with films. For both heterogenous phantoms, differences within 1 mm between measured and simulated central beam positions and widths were obtained, confirming a good agreement of the MC model. CONCLUSIONS: A GATE/Geant4 beam model for protons interacting with magnetic fields up to 1 T was developed and benchmarked to experimental data. For the first time, the GATE/Geant4 model was successfully validated not only for single energy beams, but for SOBP, in homogeneous and heterogeneous phantoms. EBT3 film dosimetry demonstrated to be a powerful dosimetric tool, once the film response function is LET corrected, for measurements in-line and transverse to the beam direction in magnetic fields. The proposed MC beam model is foreseen to support treatment planning and quality assurance (QA) activities toward MRPT.

Characterization of EBT3 radiochromic films for dosimetry of proton beams in the presence of magnetic fields.

PURPOSE: Radiochromic film dosimetry is extensively used for quality assurance in photon and proton beam therapy. So far, GafchromicTM EBT3 film appears as a strong candidate to be used in future magnetic resonance (MR) based therapy systems. The response of Gafchromic EBT3 films in the presence of magnetic fields has already been addressed for different MR-linacs systems. However, a detailed evaluation of the influence of external magnetic fields on the film response and calibration curves for proton therapy has not yet been reported. This study aims to determine the dose responses of EBT3 films for clinical proton beams exposed to magnetic field strengths up to 1 T in order to investigate the feasibility of EBT3 film as an accurate dosimetric tool for a future MR particle therapy system (MRPT). METHODS: The dosimetric characteristics of EBT3 films were studied for a proton beam passing through magnetic field strengths of B = 0, 0.5, and 1 T. Absorbed dose calibration and measurements were performed using clinical proton beams in the nominal energy range of 62.4-252.6 MeV. Irradiations were done using an in-house developed PMMA slab phantom placed in the center of a dipole research magnet. Monte Carlo (MC) simulations using the GATE/Geant4 toolkit were performed to predict the effect of magnetic fields on the energy deposited by proton beams in the phantom. Planned and measured doses from 3D box cube irradiations were compared to assess the accuracy of the dosimetric method using EBT3 films with/without the external magnetic field. RESULTS: Neither for the mean pixel value nor for the net optical density, any significant deviations were observed due to the presence of an external magnetic field (B ≤ 1T) for doses up to 10 Gy. Dose-response curves for the red channel were fitted by a three-parameter function for the field-free case and for B = 1T, showing for both cases an R-square coefficient of unity and almost identical fitting parameters. Independently of the magnetic field, EBT3 films showed an under-response as high as 8% in the Bragg peak region, similarly to previously reported effects for particle therapy. No noticeable influence of the magnetic field strength was observed on the quenching effect of the EBT3 films. CONCLUSIONS: For the first time detailed absorbed dose calibrations of EBT3 films for proton beams in magnetic field regions were performed. Results showed that EBT3 films represent an attractive solution for the dosimetry of a future MRPT system. As film response functions for protons are not affected by the magnetic field strenght, they can be used for further investigations to evaluate the dosimetric effects induced due to particle beams bending in magnetic fields regions.

Evaluation of electromagnetic and nuclear scattering models in GATE/Geant4 for proton therapy.

PURPOSE: The dose core of a proton pencil beam (PB) is enveloped by a low dose area reaching several centimeters off the central axis and containing a considerable amount of the dose. Adequate modeling of the different components of the PB profile is, therefore, required for accurate dose calculation. In this study, we experimentally validated one electromagnetic and two nuclear scattering models in GATE/Geant4 for dose calculation of proton beams in the therapeutic energy window (62-252 MeV) with and without range shifter (RaShi). METHODS: The multiple Coulomb scattering (MCS) model was validated by lateral dose core profiles measured for five energies at up to four depths from beam plateau to Bragg peak region. Nuclear halo profiles of single PBs were evaluated for three (62.4, 148.2, and 252.7 MeV) and two (97.4 and 124.7 MeV) energies, without and with RaShi, respectively. The influence of the dose core and nuclear halo on field sizes varying from 2-20 cm was evaluated by means of output factors (OFs), namely frame factors (FFs) and field size factors (FSFs), to quantify the relative increase of dose when increasing the field size. RESULTS: The relative increase in the dose core width in the simulations deviated negligibly from measurements for depths until 80% of the beam range, but was overestimated by up to 0.2 mm in σ toward the end of range for all energies. The dose halo region of the lateral dose profile agreed well with measurements in the open beam configuration, but was notably overestimated in the deepest measurement plane of the highest energy or when the beam passed through the RaShi. The root-mean-square deviations (RMSDs) between the simulated and the measured FSFs were less than 1% at all depths, but were higher in the second half of the beam range as compared to the first half or when traversing the RaShi. The deviations in one of the two tested hadron physics lists originated mostly in elastic scattering. The RMSDs could be reduced by approximately a factor of two by exchanging the default elastic scattering cross sections for protons. CONCLUSIONS: GATE/Geant4 agreed satisfyingly with most measured quantities. MCS was systematically overestimated toward the end of the beam range. Contributions from nuclear scattering were overestimated when the beam traversed the RaShi or at the depths close to the end of the beam range without RaShi. Both, field size effects and calculation uncertainties, increased when the beam traversed the RaShi. Measured field size effects were almost negligible for beams up to medium energy and were highest for the highest energy beam without RaShi, but vice versa when traversing the RaShi.

A pencil beam algorithm for magnetic resonance image-guided proton therapy.

PURPOSE: The feasibility of magnetic resonance image (MRI)-based proton therapy is based, among several other factors, on the implementation of appropriate extensions on current dose calculation methods. This work aims to develop a pencil beam algorithm (PBA) for dose calculation of proton beams within magnetic field regions of up to 3 T. METHODS: Monte Carlo (MC) simulations using the GATE 7.1/GEANT4.9.4p02 toolkit were performed to generate calibration and benchmarking data for the PBA. Dose distributions from proton beams in the clinical required energy range 60-250 MeV impinging on a 400 × 400 × 400 mm3 water phantom and transverse magnetic fields ranging from 0 to 3 T were considered. Energy depositions in homogeneous and heterogeneous phantoms filled with water, adipose, bone, and air were evaluated for proton energies of 80, 150, and 240 MeV, combining a trajectory calculation method and look-up tables (LUT). A novel parametrization model, using independent tailed Gauss fitting functions, was employed to describe the nonsymmetric shape of lateral beam profiles. Integrated depth-dose curves (IDD), lateral dose profiles, and two-dimensional dose distributions calculated with the PBA were compared with results from MC simulations to assess the performance of the algorithm. A gamma index criterion of 2%/2 mm was used for analysis. RESULTS: A close to perfect agreement was observed for PB-based dose calculations in water in magnetic fields of 0.5, 1.5, and 3 T. IDD functions showed differences between the PBA and MC of less than 0.1% before the Bragg peak, and deviations of 2-8% in the distal energy falloff region. Gamma index pass rates higher than 99% and mean values lower than 0.1 were encountered for all analyzed configurations. For homogeneous phantoms, only the full bone configuration offered deviations in the Bragg peak position of up to 1.7% and overestimations of the lateral beam spot width for high-energy protons and magnetic field intensities. An excellent agreement between PBA and MC dose calculation was also achieved using slab-like and lateral heterogeneous phantoms, with gamma index passing rates above 98% and mean values between 0.1 and 0.2. As expected, agreement reduced for high-energy protons and high-intensity magnetic fields, although results remained good enough to be considered for future implementation in clinical practice. CONCLUSIONS: The proposed pencil beam algorithm for protons can accurately account for dose distortion effects induced by external magnetic fields. The application of an analytical model for dose estimation and corrections reduces the calculation times considerably, making the presented PBA a suitable candidate for integration in a treatment planning system.

Benchmarking GATE/Geant4 for 16O ion beam therapy.

Oxygen ([Formula: see text]) ions are a potential alternative to carbon ions in ion beam therapy. Their enhanced linear energy transfer indicates a higher relative biological effectiveness and a reduced oxygen enhancement ratio. Due to the limited availability of [Formula: see text] ion beams, Monte Carlo (MC) transport codes are important research tools for investigating their potential. The purpose of this study was to validate GATE/Geant4 for [Formula: see text] ion beam therapy using experimental data from literature. Five hadron physics lists and two electromagnetic options were benchmarked against measured depth dose distributions (DDDs) and charge-changing cross sections. The simulated beam ranges deviated by less than 0.5% for all physics configurations and only a few points exceeded the gamma index criterion (2%/1 mm). However, the simulated partial charge-changing cross sections deviated considerably for some hadron physics configurations. Best agreement with the experimental values was obtained with the quantum molecular dynamics model (QMD), and we therefore suggest using this model in Geant4 to accurately describe the fragmentation of [Formula: see text] ion beams into lighter fragments ([Formula: see text]).

Magnetic field effects on particle beams and their implications for dose calculation in MR-guided particle therapy.

PURPOSE: To investigate and model effects of magnetic fields on proton and carbon ion beams for dose calculation. METHODS: In a first step, Monte Carlo simulations using Gate 7.1/Geant4.10.0.p03 were performed for proton and carbon ion beams in magnetic fields ranging from 0 to 3 T. Initial particle energies ranged from 60 to 250 MeV (protons) and 120 to 400 MeV/u (carbon ions), respectively. The resulting dose distributions were analyzed focusing on beam deflection, dose deformation, as well as the impact of material heterogeneities. In a second step, a numerical algorithm was developed to calculate the lateral beam position. Using the Runge-Kutta method, an iterative solution of the relativistic Lorentz equation, corrected for the changing particle energy during penetration, was performed. For comparison, a γ-index analysis was utilized, using a criteria of 2%/2 mm of the local maximum. RESULTS: A tilt in the dose distribution within the Bragg peak area was observed, leading to non-negligible dose distribution changes. The magnitude was found to depend on the magnetic field strength as well as on the initial beam energy. Comparison of the 3 T dose distribution with non-B field (nominal) dose distributions, resulted in a γmean (mean value of the γ distribution) of 0.6, with 14.4% of the values above 1 and γ1 % (1% of all points have an equal or higher γ value) of 1.8. The presented numerical algorithm calculated the lateral beam offset with maximum errors of less than 2% with calculation times of less than 5 µs. The impact of tissue interfaces on the proton dose distributions was found to be less than 2% for a dose voxel size of 1 × 1 × 1 mm3 . CONCLUSION: Non-negligible dose deformations at the Bragg peak area were identified for high initial energies and strong magnetic fields. A fast numerical algorithm based on the solution of the energy-corrected relativistic Lorentz equation was able to describe the beam path, taking into account the particle energy, magnetic field, and material.