Linear Energy Transfer Measurements and Estimation of Relative Biological Effectiveness in Proton and Helium Ion Beams Using Fluorescent Nuclear Track Detectors.

PURPOSE: Our objective was to develop a methodology for assessing the linear energy transfer (LET) and relative biological effectiveness (RBE) in clinical proton and helium ion beams using fluorescent nuclear track detectors (FNTDs). METHODS AND MATERIALS: FNTDs were exposed behind solid water to proton and helium (4He) ion spread-out Bragg peaks. Detectors were imaged with a confocal microscope, and the LET spectra were derived from the fluorescence intensity. The track- and dose-averaged LET (LETF and LETD, respectively) were calculated from the LET spectra. LET measurements were used as input on RBE models to estimate the RBE. Human alveolar adenocarcinoma cells (A549) were exposed at the same positions as the FNTDs. The RBE was calculated from the resulting survival curves. All measurements were compared with Monte Carlo simulations. RESULTS: For protons, average relative differences between measurements and simulations were 6% and 19% for LETF and LETD, respectively. For helium ions, the same differences were 11% for both quantities. The position of the experimental LET spectra primary peaks agreed with the simulations within 9% and 14% for protons and helium ions, respectively. For the RBE models using LETD as input, FNTD-based RBE values ranged from 1.02 ± 0.01 to 1.25 ± 0.04 and from 1.08 ± 0.09 to 2.68 ± 1.26 for protons and helium ions, respectively. The average relative differences between these values and simulations were 2% and 4%. For A549 cells, the RBE ranged from 1.05 ± 0.07 to 1.47 ± 0.09 and from 0.89 ± 0.06 to 3.28 ± 0.20 for protons and helium ions, respectively. Regarding the RBE-weighted dose (2.0 Gy at the spread-out Bragg peak), the differences between simulations and measurements were below 0.10 Gy. CONCLUSIONS: This study demonstrates for the first time that FNTDs can be used to perform direct LET measurements and to estimate the RBE in clinical proton and helium ion beams.

Ionization detail parameters and cluster dose: a mathematical model for selection of nanodosimetric quantities for use in treatment planning in charged particle radiotherapy.

Objective. To propose a mathematical model for applying ionization detail (ID), the detailed spatial distribution of ionization along a particle track, to proton and ion beam radiotherapy treatment planning (RTP).Approach. Our model provides for selection of preferred ID parameters (Ip) for RTP, that associate closest to biological effects. Cluster dose is proposed to bridge the large gap between nanoscopicIpand macroscopic RTP. Selection ofIpis demonstrated using published cell survival measurements for protons through argon, comparing results for nineteenIp:Nk,k= 2, 3, …, 10, the number of ionizations in clusters ofkor more per particle, andFk,k= 1, 2, …, 10, the number of clusters ofkor more per particle. We then describe application of the model to ID-based RTP and propose a path to clinical translation.Main results. The preferredIpwereN4andF5for aerobic cells,N5andF7for hypoxic cells. Significant differences were found in cell survival for beams having the same LET or the preferredNk. Conversely, there was no significant difference forF5for aerobic cells andF7for hypoxic cells, regardless of ion beam atomic number or energy. Further, cells irradiated with the same cluster dose for theseIphad the same cell survival. Based on these preliminary results and other compelling results in nanodosimetry, it is reasonable to assert thatIpexist that are more closely associated with biological effects than current LET-based approaches and microdosimetric RBE-based models used in particle RTP. However, more biological variables such as cell line and cycle phase, as well as ion beam pulse structure and rate still need investigation.Significance. Our model provides a practical means to select preferredIpfrom radiobiological data, and to convertIpto the macroscopic cluster dose for particle RTP.

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.

Sensitivity correction of fluorescent nuclear track detectors using alpha particles: Determining LET spectra of light ions with enhanced accuracy.

BACKGROUND: Radiation fields encountered in proton therapy (PT) and ion-beam therapy (IBT) are characterized by a variable linear energy transfer (LET), which lead to a variation of relative biological effectiveness and also affect the response of certain dosimeters. Therefore, reliable tools to measure LET are advantageous to predict and correct LET effects. Fluorescent nuclear track detectors (FNTDs) are suitable to measure LET spectra within the range of interest for PT and IBT, but so far the accuracy and precision have been challenged by sensitivity variations between individual crystals. PURPOSE: To develop a novel methodology to correct changes in the fluorescent intensity due to sensitivity variations among FNTDs. This methodology is based on exposing FNTDs to alpha particles in order to derive a detector-specific correction factor. This will allow us to improve the accuracy and precision of LET spectra measurements with FNTDs. METHODS: FNTDs were exposed to alpha particles. Afterward, the detectors were irradiated to monoenergetic protons, 4 He-, 12 C-, and 16 O-ions. At each step, the detectors were imaged with a confocal laser scanning microscope. The tracks were reconstructed and analyzed using in-house developed tools. Alpha-particle tracks were used to derive a detector-specific sensitivity correction factor ( k s , i ${k_{s,i}}$ ). Proton, 4 He-, 12 C-, and 16 O-ion tracks were used to establish a traceable calibration curve that relates the fluorescence intensity with the LET in water ( L E T H 2 O $LE{T_{{{\rm{H}}_2}{\rm{O}}}}$ ). FNTDs from a second batch were exposed and analyzed following the same procedures, to test if k s , i ${k_{s,i}}$ can be used to extend the applicability of the calibration curve to detectors from different batches. Finally, a set of blind tests was performed to assess the accuracy of the proposed methodology without user bias. Throughout all stages, the main sources of uncertainty were evaluated. RESULTS: Based on a sample of 100 FNTDs, our findings show a high sensitivity heterogeneity between FNTDs, with k s , i ${k_{s,i}}$ having values between 0.57 and 2.55. The fitting quality of the calibration curve, characterized by the mean absolute percentage residuals and correlation coefficient, was improved when k s , i ${k_{s,i}}$ was considered. Results for detectors from the second batch show that, if the fluorescence signal is corrected by k s , i ${k_{s,i}}$ , the differences in the predicted L E T H 2 O $LE{T_{{{\rm{H}}_2}{\rm{O}}}}$ with respect to the reference set are reduced from 55%, 141%, 41%, and 186% to 4.2%, 6.5%, 5.0%, and 11.0%, for protons, 4 He-, 12 C-, and 16 O-ions, respectively. The blind tests showed that it is possible to measure the track- and dose-average L E T H 2 O $LE{T_{{{\rm{H}}_2}{\rm{O}}}}$ with an accuracy of 0.3%, 16%, and 9.6% and 1.7%, 28%, and 30% for protons, 12 C-ions and mixed beams, respectively. On average, the combined uncertainty of the measured L E T H 2 O $LE{T_{{{\rm{H}}_2}{\rm{O}}}}$ was 11%, 13%, 21%, and 26% for protons, 4 He-, 12 C-, and 16 O-ions, respectively. These values were increased by a mean factor of 2.0 when k s , i ${k_{s,i}}$ was not applied. CONCLUSIONS: We have demonstrated for the first time that alpha particles can be used to derive a detector-specific sensitivity correction factor. The proposed methodology allows us to measure LET spectra using FNTD-technology, with a degree of accuracy and precision unreachable before with sole experimental approaches.

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.

Dosimetry in magnetic fields with dedicated MR-compatible ionization chambers.

MR-integrated radiotherapy requires suitable dosimetry detectors to be used in magnetic fields. This study investigates the feasibility of using dedicated MR-compatible ionization chambers at MR-integrated radiotherapy devices. MR-compatible ionization chambers (Exradin A19MR, A1SLMR, A26MR, A28MR) were precisely modeled and their relative response in a 6MV treatment beam in the presence of a magnetic field was simulated using EGSnrc. Monte Carlo simulations were carried out with the magnetic field in three orientations: the magnetic field aligned perpendicular to the chamber and beam axis (transverse orientation), the magnetic field parallel to the chamber as well as parallel to the beam axis. Monte Carlo simulation results were validated with measurements using an electromagnet with magnetic field strength upto 1.1 T with the chambers in transverse orientation. The measurements and simulation results were in good agreement, except for the A26MR ionization chamber in transverse orientation. The maximum increase in response of the ionization chambers observed was 8.6% for the transverse orientation. No appreciable change in chamber response due to the magnetic field was observed for the magnetic field parallel to the ionization chamber and parallel to the photon beam. Polarity and recombination correction factor were experimentally investigated in the transverse orientation. The polarity effect and recombination effect were not altered by a magnetic field. This study further investigates the response of the ionization chambers as a function of the chambers' rotation around their longitudinal axis. A variation in response was observed when the chamber was not rotationally symmetric, which was independent of the magnetic field.

MRI-guided proton therapy planning: accounting for an inline MRI fringe field.

MRI-guided proton therapy is being pursued for its promise to provide a more conformal, accurate proton therapy. However, the presence of the magnetic field imposes a challenge for the beam delivery as protons are deflected due to the Lorenz force. In this study, the impact of realistic inline MRI fringe field on IMPT plan delivery is investigated for a water phantom, liver tumor and prostate cancer differing in target volume, shape, and field configuration using Monte Carlo simulations. A method to correct for the shift of the beam spot positions in the presence of the inline magnetic field is presented. Results show that when not accounting for the effect of the magnetic field on the pencil beam delivery, the spot positions are substantially shifted and the quality of delivered plans is significantly deteriorated leading to dose inhomogeneities and creation of hot and cold spots. However, by correcting the pencil beam delivery, the dose quality of the IMPT plans is restored to a high degree. Nevertheless, adaptation of beam delivery alone is not robust regarding different treatment sites. By fully accounting during plan optimization for the dose distortions caused by the fringe and imaging fields, highly conformal IMPT plans are achieved. These results demonstrate proton pencil beam scanning and treatment planning can be adapted for precise delivery of state-of-the-art IMPT plans in MR-guided proton therapy in the presence of an inline MRI fringe field.

Impact of new ICRU 90 key data on stopping-power ratios and beam quality correction factors for carbon ion beams.

The recent update of key dosimetric data by the International Commission on Radiation Units and Measurements (ICRU) makes several changes to the computation of beam quality correction factors k Q with regard to, for example, the mean excitation energies, I, which enter the stopping power computation for water and air, the computation procedure itself, the average energy expended in the production of an ion pair in air, W/e, as well as chamber-specific factors for cobalt-60. With the new recommendations an accurate assessment of the water-to-air stopping-power ratio, [Formula: see text], in reference conditions is necessary to update the dosimetry protocols for carbon ion beams. The ICRU 90 key data were considered for computation of [Formula: see text] for carbon ion beams using Monte Carlo transport simulations for a number of reference conditions, namely monoenergetic carbon ion beams with a range in water from 3 to 30 cm and spread-out Bragg peaks (SOBPs) of different widths and depths in water. New recommendations for [Formula: see text] are presented, namely 1.1247 for the reference condition of depth 1 g cm-2 for monoenergetic carbon ion beams and 1.1273 at the center of physically optimized SOBPs. The recommendation of a constant value (1.126) represents the stopping-power ratio within a 0.3% variation of [Formula: see text] for all reference conditions considered. The impact of these new [Formula: see text] values and the updated key data on k Q for carbon ion beams was evaluated in a second step. Changes and the difference from experimental data were found to be non-significant, but larger discrepancies to measurements were observed for plane-parallel ionization chambers. The combined uncertainty for k Q in carbon ion beams decreased to 2.4%. In future, it could be further lowered by using chamber-specific Monte Carlo transport simulations, for which the implementation of ICRU 90 key data as done in this study is a prerequisite.

The microdosimetric extension in TOPAS: development and comparison with published data.

Microdosimetric energy depositions have been suggested as a key variable for the modeling of the relative biological effectiveness (RBE) in proton and ion radiation therapy. However, microdosimetry has been underutilized in radiation therapy. Recent advances in detector technology allow the design of new mico- and nano-dosimeters. At the same time Monte Carlo (MC) simulations have become more widely used in radiation therapy. In order to address the growing interest in the field, a microdosimetric extension was developed in TOPAS. The extension provides users with the functionality to simulate microdosimetric spectra as well as the contribution of secondary particles to the spectra, calculate microdosimetric parameters, and determine RBE with a biological weighting function approach or with the microdosimetric kinetic (MK) model. Simulations were conducted with the extension and the results were compared with published experimental data and other simulation results for three types of microdosimeters, a spherical tissue equivalent proportional counter (TEPC), a cylindrical TEPC and a solid state microdosimeter. The corresponding microdosimetric spectra obtained with TOPAS from the plateau region to the distal tail of the Bragg curve generally show good agreement with the published data.

Comparing the effectiveness and efficiency of various gating approaches for PBS proton therapy of pancreatic cancer using 4D-MRI datasets.

Abdominal organ motion may lead to considerable uncertainties in pencil-beam scanning (PBS) proton therapy of pancreatic cancer. Beam gating, where irradiation only occurs in certain breathing phases in which the gating conditions are fulfilled, may be an option to reduce the interplay effect between tumor motion and the scanning beam. This study aims to, first, determine suitable gating windows with respect to effectiveness (low interplay effect) and efficiency (high duty cycles). Second, it investigates whether beam gating allows for a better mitigation of the interplay effect along the treatment course than free-breathing irradiations. Based on synthetic 4D-CTs, generated by warping 3D-CTs with vector fields extracted from time-resolved magnetic resonance imaging (4D-MRI) for 8 pancreatic cancer patients, 4D dose calculations (4DDC) were performed to analyze the duty cycle and homogeneity index HI = d5/d95 for four different gating scenarios. These were based on either fixed threshold values of CTV (clinical target volume) mean or maximum motion amplitudes (5 mm), relative CTV motion amplitudes (30%) or CTV overlap criteria (95%), respectively. 4DDC for 28-fractions treatment courses were performed with fixed and variable initial breathing phases to investigate the fractionation-induced mitigation of the interplay effect. Gating criteria, based on patient-specific relative 30% CTV motion amplitudes, showed the significantly best HI values with sufficient duty cycles, in contrast to inferior results by either fixed gating thresholds or overlap criteria. For gated treatments with 28 fractions, less fractionation-induced mitigation of the interplay effect was observed for gating criteria with gating windows ⩾30%, compared to free-breathing treatments. The gating effectiveness for multiple fractions was improved by allowing a variable initial breathing phase. Gating with relative amplitude thresholds are effective for proton therapy of pancreatic cancer. By combining beam gating with variable initial breathing phases, a pronounced mitigation of the interplay effect by fractionation can be achieved.

Simultaneous optimization of RBE-weighted dose and nanometric ionization distributions in treatment planning with carbon ions.

Inverse treatment planning in intensity modulated particle therapy (IMPT) with scanned carbon-ion beams is currently based on the optimization of RBE-weighted dose to satisfy requirements of target coverage and limited toxicity to organs-at-risk (OARs) and healthy tissues. There are many feasible IMPT plans that meet these requirements, which allows the introduction of further criteria to narrow the selection of a biologically optimal treatment plan. We propose a novel treatment planning strategy based on the simultaneous optimization of RBE-weighted dose and nanometric ionization details (ID) as a new physical characteristic of the delivered plan beyond LET. In particular, we focus on the distribution of large ionization clusters (more than 3 ionizations) to enhance the biological effect across the target volume while minimizing biological effect in normal tissues. Carbon-ion treatment plans for different patient geometries and beam configurations generated with the simultaneous optimization strategy were compared against reference plans obtained with RBE-weighted dose optimization alone. Quality indicators, inhomogeneity index and planning volume histograms of RBE-weighted dose and large ionization clusters were used to evaluate the treatment plans. We show that with simultaneous optimization, ID distributions can be optimized in carbon-ion radiotherapy without compromising the RBE-weighted dose distributions. This strategy can potentially be used to account for optimization of endpoints closely related to radiation quality to achieve better tumor control and reduce risks of complications.

Fast calculation of nanodosimetric quantities in treatment planning of proton and ion therapy.

Details of the pattern of ionization formed by particle tracks extends knowledge of dose effects on the nanometer scale. Ionization detail (ID), frequently characterized by ionization cluster size distributions (ICSD), is obtained through time-consuming Monte Carlo (MC) track-structure simulations. In this work, TOPAS-nBio was used to generate a highly precise database of biologically significant ID quantities, sampled with randomly oriented 2.3 nm diameter cylinders, 3.4 nm (10 base pairs) long, inside a chromatin-size cylinder, irradiated by 1-1000 MeV/u ions of Z = 1-8. A macroscopic method developed to utilize the database using condensed-history MC was used to calculate distributions of the ICSD first moment [Formula: see text] and cumulative probability [Formula: see text] in a 20 × 20 × 40 cm3 water phantom irradiated with proton and carbon spread-out Bragg peak (SOBP) of 10.5 cm range, 2 cm width. Results were verified against detailed MC track-structure simulations using phase space scored at several depths. ID distributions were then obtained for intensity modulated proton and carbon radiotherapy plans in a digitized anthropomorphic phantom of a base of skull tumor to demonstrate clinical application of this approach. The database statistical uncertainties were 0.5% (3 standard deviations). Fluence-averaged ID as implemented proved unsuitable for macroscopic calculation. E dep-averaged ID agreed with track-structure results within 0.8% for protons. For carbon, maximum absolute differences of 2.9% ± 1.6% and 5.6% ± 1.9% for [Formula: see text], 1.7% ± 0.8% and 1.9% ± 0.4% (1 standard deviation) for [Formula: see text], were found in the plateau and SOBP, respectively, up to 11.5% ± 5.6% in the tail region. Macroscopic ID calculation was demonstrated for a realistic treatment plan. Computation times with or without ID calculation were comparable in all cases. Pre-calculated nanodosimetric data may be used for condensed-history MC for nanodosimetric ID-based treatment planning in ion radiotherapy in the future. The macroscopic approach developed has the calculation speed of condensed-history MC while approaching the accuracy of full track structure simulations.

The effect of density overrides on magnetic resonance-guided radiation therapy planning for lung cancer.

BACKGROUND AND PURPOSE: Inverse treatment planning for lung cancer can be challenging since density heterogeneities may appear inside the planning target volume (PTV). One method to improve the quality of intensity modulation is the override of low density tissues inside the PTV during plan optimization. For magnetic resonance-guided radiation therapy (MRgRT), where the influence of the magnetic field on secondary electrons is sensitive to the tissue density, the reliability of density overrides has not yet been proven. This work, therefore, gains a first insight into density override strategies for MRgRT. MATERIAL AND METHODS: Monte Carlo-based treatment plans for five lung cancer patients were generated based on free-breathing CTs and two density override strategies. Different magnetic field configurations were considered with their effect being accounted for during optimization. Optimized plans were forward calculated to 4D-CTs and accumulated for the comparison of planned and expected delivered dose. RESULTS: For MRgRT, density overrides led to a discrepancy between the delivered and planned dose. The tumor volume coverage deteriorated for perpendicular magnetic fields of 1.5 T to 93.6% (D98%). For inline fields a maximal increase of 2.2% was found for the mean dose. In terms of organs at risk, a maximal sparing of 0.6 Gy and 0.9 Gy was observed for lung and heart, respectively. CONCLUSIONS: In this work, first results on the effect of density overrides on treatment planning for MRgRT are presented. It was observed that the underestimation of magnetic field effects in overridden densities during treatment planning resulted in an altered delivered dose, depending on the field strength and orientation.

A novel method for assessment of fragmentation and beam-material interactions in helium ion radiotherapy with a miniaturized setup.

Radiotherapy with protons and carbon ions enables to deliver dose distributions of high conformation to the target. Treatment with helium ions has been suggested due to their physical and biological advantages. A reliable benchmarking of the employed physics models with experimental data is required for treatment planning. However, experimental data for helium interactions is limited, in part due to the complexity and large size of conventional experimental setups. We present a novel method for the investigation of helium interactions with matter using miniaturized instrumentation based on highly integrated pixel detectors. The versatile setup consisted of a monitoring detector in front of the PMMA phantom of varying thickness and a detector stack for investigation of outgoing particles. The ion type downstream from the phantom was determined by high-resolution pattern recognition analysis of the single particle signals in the pixelated detectors. The fractions of helium and hydrogen ions behind the used targets were determined. As expected for the stable helium nucleus, only a minor decrease of the primary ion fluence along the target depth was found. E.g. the detected fraction of hydrogen ions on axis of a 220MeV/u 4He beam was below 6% behind 24.5cm of PMMA. Monte-Carlo simulations using Geant4 reproduce the experimental data on helium attenuation and yield of helium fragments qualitatively, but significant deviations were found for some combinations of target thickness and beam energy. The presented method is promising to contribute to the reduction of the uncertainty of treatment planning for helium ion radiotherapy.

Effects of magnetic field orientation and strength on the treatment planning of nonsmall cell lung cancer.

PURPOSE: Magnetic resonance image-guided radiotherapy (MRgRT) has the potential to increase the accuracy of radiation treatment delivery. Several research groups have developed hybrid MRgRT devices differing by radiation source used and magnetic field orientation and strength. In this work, we investigate the impact of different magnetic field orientations and strengths on the treatment planning of nonsmall cell lung cancer patients (NSCLC). METHODS: A framework using the in-house developed treatment planning system matRad and the EGSnrc Monte Carlo code system was introduced to perform Monte Carlo-based treatment planning in the presence of a magnetic field. A specialized spectrum-based source model for the beam qualities of 6 MV and cobalt-60 was applied. Optimized plans for stereotactic body radiation therapy (SBRT) and intensity-modulated radiation therapy (IMRT) were generated for four NSCLC patients in the presence of different magnetic field orientations and strengths which are applied in hybrid MRgRT devices currently under development or in clinical use. RESULTS: SBRT and IMRT treatment planning could be performed with consistent plan quality for all magnetic field setups. Only minor effects on the treatment planning outcome were found in the case of magnetic fields orientated perpendicular to the beam direction. Compared to the perpendicular magnetic field orientation, the inline orientation showed the capability to reduce the dose to lung while maintaining equal target coverage. Particularly for tumors with a central position in lung, a distinct dose reduction was obtained which led to a maximum reduction of mean lung dose by 18.5% (0.5 Gy), when applying a 1 T inline magnetic field. CONCLUSION: All plans generated in this work obtained dose metrics within clinical constraints according to RTOG guidelines. When considering conventional dose metrics, no detrimental effects due to the magnetic fields were observed on the dose to the tumor or to organs at risk. An evaluation of the effects on skin dose was not ascertainable due to the simplified specification of the source model used. By accounting for the magnetic field during treatment planning, a dose reduction in lung could be achieved for inline-oriented magnetic fields. An inline orientation of the magnetic field therefore showed a potential benefit when treating NSCLC with MRgRT.

Lateral variations of radiobiological properties of therapeutic fields of 1H, 4He, 12C and 16O ions studied with Geant4 and microdosimetric kinetic model.

As known, in cancer therapy with ion beams the relative biological effectiveness (RBE) of ions changes in the course of their propagation in tissues. Such changes are caused not only by increasing the linear energy transfer (LET) of beam particles with the penetration depth towards the Bragg peak, but also by nuclear reactions induced by beam nuclei leading to the production of various secondary particles. Although the changes of RBE along the beam axis have been studied quite well, much less attention has been paid to the evolution of RBE in the transverse direction, perpendicular to the beam axis. In order to fill this gap, we simulated radiation fields of 1H, 4He, 12C and 16O nuclei of 20 mm in diameter by means of a Geant4-based Monte Carlo model for heavy-ion therapy connected with the modified microdosimetric kinetic model to describe the response of normal ([Formula: see text] Gy) and early-responding ([Formula: see text] Gy) tissues. Depth and radial distributions of saturation-corrected dose-mean lineal energy, RBE and RBE-weighted dose are investigated for passive beam shaping and active beam scanning. The field of 4He has a small lateral spread as compared with 1H field, and it is characterised by a modest lateral variation of RBE suggesting the use of fixed RBE values across the field transverse cross section at each depth. Reduced uncertainties of RBE on the boundary of a 4He treatment field can be advantageous in a specific case of an organ at risk located in lateral proximity to the target volume. It is found that the lateral distributions of RBE calculated for 12C and 16O fields demonstrate fast variations in the radial direction due to changes of dose and composition of secondary fragments in the field penumbra. Nevertheless, the radiation fields of all four projectiles at radii larger than 20 mm can be characterized by a common RBE value defined by tissue radiosensitivity. These findings can help, in particular, in accessing the transverse homogeneity of radiation fields of ions used in studies in vitro.

Development of the open-source dose calculation and optimization toolkit matRad.

PURPOSE: We report on the development of the open-source cross-platform radiation treatment planning toolkit matRad and its comparison against validated treatment planning systems. The toolkit enables three-dimensional intensity-modulated radiation therapy treatment planning for photons, scanned protons and scanned carbon ions. METHODS: matRad is entirely written in Matlab and is freely available online. It re-implements well-established algorithms employing a modular and sequential software design to model the entire treatment planning workflow. It comprises core functionalities to import DICOM data, to calculate and optimize dose as well as a graphical user interface for visualization. matRad dose calculation algorithms (for carbon ions this also includes the computation of the relative biological effect) are compared against dose calculation results originating from clinically approved treatment planning systems. RESULTS: We observe three-dimensional γ-analysis pass rates ≥ 99.67% for all three radiation modalities utilizing a distance to agreement of 2 mm and a dose difference criterion of 2%. The computational efficiency of matRad is evaluated in a treatment planning study considering three different treatment scenarios for every radiation modality. For photons, we measure total run times of 145 s-1260 s for dose calculation and fluence optimization combined considering 4-72 beam orientations and 2608-13597 beamlets. For charged particles, we measure total run times of 63 s-993 s for dose calculation and fluence optimization combined considering 9963-45574 pencil beams. Using a CT and dose grid resolution of 0.3 cm3 requires a memory consumption of 1.59 GB-9.07 GB and 0.29 GB-17.94 GB for photons and charged particles, respectively. CONCLUSION: The dosimetric accuracy, computational performance and open-source character of matRad encourages a future application of matRad for both educational and research purposes.

Evaluation of the acromiohumeral distance by means of magnetic resonance imaging umerus.

OBJECTIVE: To demonstrate the relationship between the size, degree of retraction and topography of rotator cuff injuries and the degree of rise of the humeral head, and to evaluate the influence of gravity, using magnetic resonance imaging (MRI). METHODS: We evaluated 181 shoulder MRIs from 160 patients aged over 45 years, between November 2013 and July 2014. The patients were divided into two groups: one control (no lesion or partial damage to the rotator cuff); and the other with complete tears of the rotator cuff. We measured the acromiohumeral distance in the sagittal plane, and established the shortest distance between the apex of the head and the acromion. RESULTS: In this study, 96 examinations on female patients (53.04%) and 58 on male patients (46.96%) were evaluated. The mean age was 63.27 years: in the control group, 61.46; and in the group with injuries, 65.19. From analysis on the measurements of the subacromial space, we observed significantly higher values in the control group (7.71 mm) than in the group with injuries (6.99). In comparing the control group with some specific subgroup, i.e. posterosuperior (6.77), anteroposterior-superior (4.16) and retraction Patte III (5.01), we confirmed the importance of topography and degree of retraction in relation to the rise of the humeral head. CONCLUSION: The rise of the humeral head was directly related to the size, degree of retraction and topography of the rotator cuff injuries, with greater degrees of rise in cases of superior and posterior lesions and anteroposterior-superior (massive) lesions. The assessment using MRI was not influenced by the force of gravity.

OBJETIVO: Demonstrar a relação entre o tamanho, grau de retração e topografia das lesões do manguito rotador com o grau de ascensão da cabeça umeral e avaliar a influência da força da gravidade na ressonância magnética. MÉTODOS: Avaliamos 181 ressonâncias magnéticas de ombro de 160 pacientes com mais de 45 anos, entre novembro de 2013 e julho de 2014. Os pacientes eram divididos em dois grupos, um de controle (sem lesão ou com lesão parcial do MR) e outro com lesão completa do MR. Fizemos a mensuração da distância acrômio-umeral nos cortes sagitais e foi estabelecida a menor distância entre o ápice da cabeça e o acrômio. RESULTADOS: Foram avaliados neste estudo 96 (53,04%) exames de pacientes do sexo feminino e 58 de pacientes do sexo masculino (46,96%). A idade média foi 63,27 anos, a do grupo controle 61,46 e a do grupo com lesão 65,19. Ao analisar as medidas do espaço subacromial, observamos valores significativamente maiores no grupo controle (7,71 mm) do que no grupo com lesão (6,99). Quando comparamos o grupo controle com alguns subgrupos específicos, posterossuperior (6,77), anteroposterossuperior (4,16) e retração Patte III (5,01), confirmamos a importância da topografia e grau de retração para ascensão da cabeça umeral. CONCLUSÃO: A ascensão da cabeça umeral tem relação direta com o tamanho, grau de retração e a topografia das lesões do manguito rotador, com graus maiores de ascensão nas lesões posterossuperiores e anteroposterossuperiores (extensas). A avaliação feita pela ressonância magnética não sofre influência da força da gravidade.

Distributions of deposited energy and ionization clusters around ion tracks studied with Geant4 toolkit.

The Geant4-based Monte Carlo model for Heavy-Ion Therapy (MCHIT) was extended to study the patterns of energy deposition at sub-micrometer distance from individual ion tracks. Dose distributions for low-energy (1)H, (4)He, (12)C and (16)O ions measured in several experiments are well described by the model in a broad range of radial distances, from 0.5 to 3000 nm. Despite the fact that such distributions are characterized by long tails, a dominant fraction of deposited energy (∼80%) is confined within a radius of about 10 nm. The probability distributions of clustered ionization events in nanoscale volumes of water traversed by (1)H, (2)H, (4)He, (6)Li, (7)Li, and (12)C ions are also calculated. A good agreement of calculated ionization cluster-size distributions with the corresponding experimental data suggests that the extended MCHIT can be used to characterize stochastic processes of energy deposition to sensitive cellular structures.

Evaluation of the acromiohumeral distance by means of magnetic resonance imaging umerus / Avaliação da distância úmero-acromial por meio da ressonância magnética

OBJECTIVE: To demonstrate the relationship between the size, degree of retraction and topography of rotator cuff injuries and the degree of rise of the humeral head, and to evaluate the influence of gravity, using magnetic resonance imaging (MRI). METHODS: We evaluated 181 shoulder MRIs from 160 patients aged over 45 years, between November 2013 and July 2014. The patients were divided into two groups: one control (no lesion or partial damage to the rotator cuff); and the other with complete tears of the rotator cuff. We measured the acromiohumeral distance in the sagittal plane, and established the shortest distance between the apex of the head and the acromion. RESULTS: In this study, 96 examinations on female patients (53.04%) and 58 on male patients (46.96%) were evaluated. The mean age was 63.27 years: in the control group, 61.46; and in the group with injuries, 65.19. From analysis on the measurements of the subacromial space, we observed significantly higher values in the control group (7.71 mm) than in the group with injuries (6.99). In comparing the control group with some specific subgroup, i.e. posterosuperior (6.77), anteroposterior-superior (4.16) and retraction Patte III (5.01), we confirmed the importance of topography and degree of retraction in relation to the rise of the humeral head. CONCLUSION: The rise of the humeral head was directly related to the size, degree of retraction and topography of the rotator cuff injuries, with greater degrees of rise in cases of superior and posterior lesions and anteroposterior-superior (massive) lesions. The assessment using MRI was not influenced by the force of gravity.

OBJETIVO: Demonstrar a relação entre o tamanho, grau de retração e topografia das lesões do manguito rotador com o grau de ascensão da cabeça umeral e avaliar a influência da força da gravidade na ressonância magnética. MÉTODOS: Avaliamos 181 ressonâncias magnéticas de ombro de 160 pacientes com mais de 45 anos, entre novembro de 2013 e julho de 2014. Os pacientes eram divididos em dois grupos, um de controle (sem lesão ou com lesão parcial do MR) e outro com lesão completa do MR. Fizemos a mensuração da distância acrômio-umeral nos cortes sagitais e foi estabelecida a menor distância entre o ápice da cabeça e o acrômio. RESULTADOS: Foram avaliados neste estudo 96 (53,04%) exames de pacientes do sexo feminino e 58 de pacientes do sexo masculino (46,96%). A idade média foi 63,27 anos, a do grupo controle 61,46 e a do grupo com lesão 65,19. Ao analisar as medidas do espaço subacromial, observamos valores significativamente maiores no grupo controle (7,71 mm) do que no grupo com lesão (6,99). Quando comparamos o grupo controle com alguns subgrupos específicos, posterossuperior (6,77), anteroposterossuperior (4,16) e retração Patte III (5,01), confirmamos a importância da topografia e grau de retração para ascensão da cabeça umeral. CONCLUSÃO: A ascensão da cabeça umeral tem relação direta com o tamanho, grau de retração e a topografia das lesões do manguito rotador, com graus maiores de ascensão nas lesões posterossuperiores e anteroposterossuperiores (extensas). A avaliação feita pela ressonância magnética não sofre influência da força da gravidade.