Monte Carlo simulation for proton dosimetry in magnetic fields: Fano test and magnetic field correction factorskBfor Farmer-type ionization chambers.

Objective. In this contribution we present a special Fano test for charged particles in presence of magnetic fields in the MC code TOol for PArticle Simulation (TOPAS), as well as the determination of magnetic field correction factorskBfor Farmer-type ionization chambers using proton beams.Approach. Customized C++ extensions for TOPAS were implemented to model the special Fano tests in presence of magnetic fields for electrons and protons. The Geant4-specific transport parameters,DRoverRandfinalRange,were investigated to optimize passing rate and computation time. ThekBwas determined for the Farmer-type PTW 30013 ionization chamber, and 5 custom built ionization chambers with same geometry but varying inner radius, testing magnetic flux density ranging from 0 to 1.0 T and two proton beam energies of 157.43 and 221.05 MeV.Main results. Using the investigated parameters, TOPAS passed the Fano test within 0.39 ± 0.15% and 0.82 ± 0.42%, respectively for electrons and protons. The chamber response (kB,M,Q) gives a maximum at different magnetic flux densities depending of the chamber size, 1.0043 at 1.0 T for the smallest chamber and 1.0051 at 0.2 T for the largest chamber. The local dose differencecBremained ≤ 0.1% for both tested energies. The magnetic field correction factorkB, for the chamber PTW 30013, varied from 0.9946 to 1.0036 for both tested energies.Significance. The developed extension for the special Fano test in TOPAS MC code with the adjusted transport parameters, can accurately transport electron and proton particles in magnetic field. This makes TOPAS a valuable tool for the determination ofkB. The ionization chambers we tested showed thatkBremains small (≤0.72%). To the best of our knowledge, this is the first calculations ofkBfor proton beams. This work represents a significant step forward in the development of MRgPT and protocols for proton dosimetry in presence of magnetic field.

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.

Technical note: Experimental dosimetric characterization of proton pencil beam distortion in a perpendicular magnetic field of an in-beam MR scanner.

BACKGROUND: As it promises more precise and conformal radiation treatments, magnetic resonance imaging-integrated proton therapy (MRiPT) is seen as a next step in image guidance for proton therapy. The Lorentz force, which affects the course of the proton pencil beams, presents a problem for beam delivery in the presence of a magnetic field. PURPOSE: To investigate the influence of the 0.32-T perpendicular magnetic field of an MR scanner on the delivery of proton pencil beams inside an MRiPT prototype system. METHODS: An MRiPT prototype comprising of a horizontal pencil beam scanning beam line and an open 0.32-T MR scanner was used to evaluate the impact of the vertical magnetic field on proton beam deflection and dose spot pattern deformation. Three different proton energies (100, 150, and 220 MeV) and two spot map sizes (15 × 15 and 30 × 20 cm2 ) at four locations along the beam path without and with magnetic field were measured. Pencil-beam dose spots were measured using EBT3 films and a 2D scintillation detector. To study the magnetic field effects, a 2D Gaussian fit was applied to each individual dose spot to determine the central position ( X , Y ) $(X,Y)$ , minimum and maximum lateral standard deviation ( σ m i n $\sigma _{min}$ and σ m a x $\sigma _{max}$ ), orientation (θ), and the eccentricity (ε). RESULTS: The dose spots were subjected to three simultaneous effects: (a) lateral horizontal beam deflection, (b) asymmetric trapezoidal deformation of the dose spot pattern, and (c) deformation and rotation of individual dose spots. The strongest effects were observed at a proton energy of 100 MeV with a horizontal beam deflection of 14-186 mm along the beam path. Within the central imaging field of the MR scanner, the maximum relative dose spot size σ m a x $\sigma _{max}$ decreased by up to 3.66%, while σ m i n $\sigma _{min}$ increased by a maximum of 2.15%. The largest decrease and increase in the eccentricity of the dose spots were 0.08 and 0.02, respectively. The spot orientation θ was rotated by a maximum of 5.39°. At the higher proton energies, the same effects were still seen, although to a lesser degree. CONCLUSIONS: The effect of an MRiPT prototype's magnetic field on the proton beam path, dose spot pattern, and dose spot form has been measured for the first time. The findings show that the impact of the MF must be appropriately recognized in a future MRiPT treatment planning system. The results emphasize the need for additional research (e.g., effect of magnetic field on proton beams with range shifters and impact of MR imaging sequences) before MRiPT applications can be employed to treat patients.

Proton beam dosimetry in the presence of magnetic fields using Farmer-type ionization chambers of different radii.

BACKGROUND: Magnetic resonance-guided proton therapy is promising, as it combines high-contrast imaging of soft tissue with highly conformal dose delivery. However, proton dosimetry in magnetic fields using ionization chambers is challenging since the dose distribution as well as the detector response are perturbed. PURPOSE: This work investigates the effect of the magnetic field on the ionization chamber response, and on the polarity and ion recombination correction factors, which are essential for the implementation of a proton beam dosimetry protocol in the presence of magnetic fields. METHODS: Three Farmer-type cylindrical ionization chambers, the 30013 with 3 mm inner radius (PTW, Freiburg, Germany) and two custom built chambers "R1" and "R6" with 1 and 6 mm inner radii respectively were placed at the center of an experimental electromagnet (Schwarzbeck Mess - Elektronik, Germany) 2 cm depth of an in-house developed 3D printed water phantom. The detector response was measured for a 3 × 10 cm2 field of mono-energetic protons 221.05 MeV/u for the three chambers, and with an additional proton beam of 157.43 MeV/u for the chamber PTW 30013. The magnetic flux density was varied between 0.1 and 1.0 Tesla in steps of 0.1 Tesla. RESULTS: At both energies, the ionization chamber PTW 30013 showed a non-linear response as a function of the magnetic field strength, with a decrease of the ionization chamber response of up to 0.27% ± 0.06% (1 SD) at 0.2 Tesla, followed by a smaller effect at higher magnetic field strength. For the chamber R1, the response decreased slightly with the magnetic field strength up to 0.45% ± 0.12% at 1 Tesla, and for the chamber R6, the response decreased up to 0.54% ± 0.13% at 0.1 Tesla, followed by a plateau up to 0.3 Tesla, and a weaker effect at higher magnetic field strength. The dependence of the polarity and recombination correction factor on the magnetic field was ⩽0.1% for the chamber PTW 30013. CONCLUSIONS: The magnetic field has a small but significant effect on the chamber response in the low magnetic field region for the chamber PTW 30013 and for R6, and in the high magnetic field region for the chamber R1. Corrections may be necessary for ionization chamber measurements, depending on both the chamber volume and the magnetic flux density. No significant effect of the magnetic field on the polarity and recombination correction factor was detected in this work for the ionization chamber PTW 30013.

Reduction of intrafraction pancreas motion using an abdominal corset compatible with proton therapy and MRI.

Background and purpose: Motion mitigation is of crucial importance in particle therapy (PT) of patients with abdominal tumors to ensure high-precision irradiation. Magnetic resonance imaging (MRI) is an excellent modality for target volume delineation and motion estimation of mobile soft-tissue tumors. Thus, the aims of this study were to develop an MRI- and PT-compatible abdominal compression device, to investigate its effect on pancreas motion reduction, and to evaluate patient tolerability and acceptance. Materials and methods: In a prospective clinical study, 16 patients with abdominal tumors received an individualized polyethylene-based abdominal corset. Pancreas motion was analyzed using time- and phase resolved MRI scans (orthogonal 2D-cine and 4D MRI) with and without compression by the corset. The pancreas was manually segmented in each MRI data set and the population-averaged center-of-mass motion in inferior-superior (IS), anterior-posterior (AP) and left-right (LR) directions was determined. A questionnaire was developed to investigate the level of patient acceptance of the corset, which the patients completed after acquisition of the planning computed tomography (CT) and MRI scans. Results: The corset was found to reduce pancreas motion predominantly in IS direction by on average 47 % - 51 % as found in the 2D-cine and 4D MRI data, respectively, while motion in the AP and LR direction was not significantly reduced. Most patients reported no discomfort when wearing the corset. Conclusion: An MRI- and PT-compatible individualized abdominal corset was presented, which substantially reduced breathing-induced pancreas motion and can be safely applied with no additional discomfort for the patients. The corset has been successfully integrated into our in-house clinical workflow for PT of tumors of the upper abdomen.

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.

An initial systematic study of the linear energy transfer distributions of a proton beam under a transverse magnetic field.

PURPOSE: To evaluate the biological effectiveness of magnetic resonance (MR)-guided proton beam therapy, comprehensively characterizing the dose and dose-averaged linear energy transfer (LETd ) distributions under a magnetic field is necessary. Although detailed analysis has characterized curved beam paths and distorted dose distributions, the impact of a magnetic field on LETd should also be explored to determine the proton relative biological effectiveness (RBE). Hence, this initial study aims to present a basic analysis of LETd distributions in the presence of a magnetic field using Monte Carlo simulation (MCS). METHODS: Geant4 MCS (version 10.1.p01) was performed to calculate the LETd distribution of proton beams. The incident beam energies were set to 70.2, 140.8, and 220 MeV, and both zero- and finite-emittance pencil beams as well as scanned field were simulated. A transverse magnetic field of 0-3 T was applied within a water phantom placed at the isocenter, and the three-dimensional dose and LETd distributions in the phantom were calculated. Then, the depth profiles of LETd along the curved trajectory and the lateral LETd profile at the Bragg peak (BP) depth were analyzed under changing energies and magnetic fields. In addition, for zero- and finite-emittance beams, the correlation of the lateral asymmetries between the dose and LETd distributions were analyzed. Finally, spread-out Bragg peak (SOBP) fields were simulated to assess the depth-dependent asymmetry of the LETd distributions. RESULTS: A transverse magnetic field distorted the lateral LETd distribution of a pencil beam at close to the BP, and the magnitude of the distortion at the BP increased for higher energy beams and larger magnetic fields. For a zero-emittance beam, the differences in LETd between the left and right D20 positions were relatively large; the difference in LETd was 1.5 and 2.3 keV/µm at 140.8 and 220 MeV, respectively, at a magnetic field of 1.5 T. These asymmetries were pronounced at positions where the dose asymmetries were large. The size of the asymmetry was less substantial for a finite-emittance beam and even less for a scanned field. However, a 1.5-keV/µm difference still remained between the left and right D20 positions of a scanned field penumbra for a 220 MeV beam under the same magnetic field. For the SOBP field, it was found that the distal region of SOBP had the highest LETd distortions, followed by the central and proximal regions for the middle-sized SOBP (5 × 5 × 5 cm3 ), whereas the degree of LETd distortion did not vary much with depth for the 10 × 10 × 10-cm3 SOBP field. CONCLUSION: Our results indicate that not only the dose but also LETd distortions should be considered to accurately evaluate the biological effectiveness of MR-guided proton beam therapy.

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.

Integrated MRI-guided proton therapy planning: Accounting for the full MRI field in a perpendicular system.

PURPOSE: To present a first study on the treatment planning feasibility in perpendicular field MRI-integrated proton therapy that considers the full transport of protons from the pencil beam scanning (PBS) assembly to the patient inside the MRI scanner. METHODS: A generic proton PBS gantry was modeled as being integrated with a realistic split-bore MRI system in the perpendicular orientation. MRI field strengths were modeled as 0.5, 1, and 1.5 T. The PBS beam delivery and dose calculation was modeled using the TOPAS Monte Carlo toolkit coupled with matRad as the optimizer engine. A water phantom, liver, and prostate plans were evaluated and optimized in the presence of the full MRI field distribution. A simple combination of gantry angle offset and small PBS nozzle skew was used to direct the proton beams along a path that closely follows the reference planning scenario, that is, without magnetic field. RESULTS: All planning metrics could be successfully achieved with the inclusion of gantry angle offsets in the range of 8 ∘ $^{\circ }$ -29 ∘ $^{\circ }$ when coupled with a PBS nozzle skew of 1.6 ∘ $^{\circ }$ -4.4 ∘ $^{\circ }$ . These two hardware-based corrections were selected to minimize the average Euclidean distance (AED) in the beam path enabling the proton beams to travel inside the patient in a path that is close to the original path (AED smaller than 3 mm at 1.5 T). Final dose optimization, performed through further changes in the PBS delivery, was then shown to be feasible for our selection of plans studied yielding comparable plan quality metrics to reference conditions. CONCLUSIONS: For the first time, we have shown a robust method to account for the full proton beam deflection in a perpendicular orientation MRI-integrated proton therapy. These results support the ongoing development of the current prototype systems.

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.