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.

The ADAM-pelvis phantom-an anthropomorphic, deformable and multimodal phantom for MRgRT.

Applicability and accuracy of the rapidly developing tools and workflows for image-guided radiotherapy need to be validated under realistic treatment-like conditions. We present the construction of the ADAM-pelvis phantom, an anthropomorphic, deformable and multimodal (CT and MRI) phantom of the male pelvis. The phantom covers patient-like uncertainties in image-guided radiotherapy workflows including imaging artifacts for the special case of the human anatomy as well as organ motion. Principles and methods were further improved from previous work. The phantom includes surrogates for muscle tissue, adipose, inner and outer bone, as well as deformable silicone organs. Anthropomorphic shapes are realized with 3D-printing techniques for the bone and the construction of the hollow silicone organ shells. Organs are constructed from patient image segmentation and further guided by reported deformation models. Imaging markers and pockets for dosimeters are included in the organ shells. The improved phantom surrogates match imaging characteristics in MRI (T1 and T2 relaxation time) and CT (Hounsfield units) of human tissues. The surrogates are suited for long term use (several months) of the phantom. Previously reported artifacts of the muscle surrogate were avoided by improved composition of the used agarose gel. Interfractional organ motion is successfully realized for the water filled bladder and the air filled rectum and showed to be reproducible with deviation below 1 mm. Volume variations of both induce displacement, rotation and deformation of the prostate. We present solutions for the construction of an anthropomorphic phantom suitable for MRI and CT imaging including deformable organs. The developed concepts of phantom surrogates and construction techniques were successfully applied in building the ADAM-pelvis phantom and can as well be adopted for other anthropomorphic phantoms. The presented phantom allows for the systematic and controlled investigation of image-guided radiotherapy workflows in presence of organ motion.

The characterization of a large multi-axis ionization chamber array in a 1.5 T MRI linac.

By combining magnetic resonance imaging (MRI) scanners and radiotherapy treatment units the need arises for new radiation measurement equipment that can be used in the magnetic field of the MRI. This study describes the investigation of the influence of the 1.5 T magnetic field from an MRI linac on the STARCHECKMAXI MR, a large 2D ionization chamber detector panel. Measurements were performed on an MRI linac and a conventional linac to investigate the behaviour of the detector panel with and without the 1.5 T magnetic field. We measured reproducibility, linearity, warm-up effect, saturation/recombination and chamber orientation. A comparison with gafchromic film was performed and the effect of motion of the panel during measurements inside a magnetic field was investigated. The reproducibility, linearity, warm-up effect, saturation/recombination show no significant deviations with or without magnetic field. An absolute difference in reading of 2.1% was found between off-axis chambers on different axes. The comparison with film shows good agreement. Spurious readings are induced while the panel is undergoing a motion in the magnetic field during measurements. The STARCHECKMAXI MR is suited for use in a 1.5 T MRI linac. Care must be taken when comparing un-normalized profiles from different axes of the detector panel and when the panel is undergoing motion during measurements.

Radiation dosimetry in magnetic fields with Farmer-type ionization chambers: determination of magnetic field correction factors for different magnetic field strengths and field orientations.

The aim of this work was to determine magnetic field correction factors that are needed for dosimetry in hybrid devices for MR-guided radiotherapy for Farmer-type ionization chambers for different magnetic field strengths and field orientations. The response of six custom-built Farmer-type chambers irradiated at a 6 MV linac was measured in a water tank positioned in a magnet with magnetic field strengths between 0.0 T and 1.1 T. Chamber axis, beam and magnetic field were perpendicular to each other and both magnetic field directions were investigated. EGSnrc Monte Carlo simulations were compared to the measurements and simulations with different field orientations were performed. For all geometries, magnetic field correction factors, [Formula: see text], and perturbation factors were calculated. A maximum increase of 8.8% in chamber response was measured for the magnetic field perpendicular to chamber and beam axis. The measured chamber response could be reproduced by adjusting the dead volume layer near the chamber stem in the Monte Carlo simulations. For the magnetic field parallel to the chamber axis or parallel to the beam, the simulated response increased by 1.1% at maximum for field strengths up to 1.1 T. A complex dependence of the response was found on chamber radius, magnetic field strength and orientation of beam, chamber axis and magnetic field direction. Especially for magnetic fields perpendicular to beam and chamber axis, the exact sensitive volume has to be considered in the simulations. To minimize magnetic field correction factors and the influence of dead volumes on the response of Farmer chambers, a measurement set-up with the magnetic field parallel to the chamber axis or parallel to the beam is recommended for dosimetry.

STED microscopy visualizes energy deposition of single ions in a solid-state detector beyond diffraction limit.

Fluorescent nuclear track detectors (FNTDs) allow for visualization of single-particle traversal in clinical ion beams. The point spread function of the confocal readout has so far hindered a more detailed characterization of the track spots-the ion's characteristic signature left in the FNTD. Here we report on the readout of the FNTD by optical nanoscopy, namely stimulated emission depletion microscopy. It was firstly possible to visualize the track spots of carbon ions and protons beyond the diffraction limit of conventional light microscopy with a resolving power of approximately 80 nm (confocal: 320 nm). A clear discrimination of the spatial width, defined by the full width half maximum of track spots from particles (proton and carbon ions), with a linear energy transfer (LET) ranging from approximately 2-1016 keV µm-1 was possible. Results suggest that the width depends on LET but not on particle charge within the uncertainties. A discrimination of particle type by width thus does not seem possible (as well as with confocal microscopy). The increased resolution, however, could allow for refined determination of the cross-sectional area facing substantial energy deposition. This work could pave the way towards development of optical nanoscopy-based analysis of radiation-induced cellular response using cell-fluorescent ion track hybrid detectors.

Application of fluorescent nuclear track detectors for cellular dosimetry.

Ion beams radiotherapy with charged particles show greater relative biological effectiveness (RBE) compared to conventional photon therapy. This enhanced RBE is due to a localized energy deposition pattern, which is subject to large fluctuations on cellular scales. Fluorescent nuclear track detectors (FNTDs) based on Al2O3:C,Mg crystals coated with cells (Cell-Fit-HD) can provide information on individual cellular energy deposition. In this study we provide a theoretical framework to obtain the distribution of microscopic energy deposition and ionization density in cells exposed to ion beams and identifies contributions of five different sources of variations to the overall energy fluctuation at different depths of a biologically optimized spread-out Bragg peak. We show that fluctuation in the individual energy loss of the particles is the major source of variability while the fluctuation in particle hits plays a minor role. With the Cell-Fit-HD system the uncertainty arising from four of these sources, namely the nucleus area, the number of nuclear hits, the particle linear energy transfer and the chord length can be reduced and only energy loss straggling remains fundamentally unknown. The ability to quantify these factors results in a reduction of the uncertainty in cellular energy deposition from 24-55% down to only 7-12%. We have also shown current experimental results with FNTDs which show promising results, but need further improvements to reach the ideals predicted in this study.

Direct determination of k Q for Farmer-type ionization chambers in a clinical scanned carbon ion beam using water calorimetry.

Until now, the dosimetry of carbon ions with ionization chambers has not reached the same level of accuracy as that of high-energy photons. This is mainly caused by the approximately threefold larger uncertainty of the k Q factor of ionization chambers, which, due to the lack of experimental data, is still derived by calculations. Measurements of absorbed dose to water, D w, by means of water calorimetry have now been performed in the entrance channel of a scanned 6 cm × 6 cm radiation field of 429 MeV/u carbon ions, allowing the direct calibration of ionization chambers and thus the experimental determination of k Q. Within this work, values for k Q have been determined for the Farmer-type ionization chambers FC65-G and TM30013. A detailed investigation of the radiation field enabled the accurate determination of correction factors needed for both calorimetric and ionometric measurements. Finally, a relative standard measurement uncertainty of 0.8% (k = 1) could be achieved for the experimental k Q values. For both chambers, the experimental k Q factors were found to be about 1% larger than those tabulated in the German DIN 6801-1 protocol, whereas compared to the theoretical values stated in the TRS-398 protocol, the experimental k Q value agrees within 0.4% for the TM30013 chamber but is about 1% lower in the case of the FC65-G chamber.

Registration procedure for spatial correlation of physical energy deposition of particle irradiation and cellular response utilizing cell-fluorescent ion track hybrid detectors.

The hybrid technology cell-fluorescent ion track hybrid detector (Cell-Fit-HD) enables the investigation of radiation-related cellular events along single ion tracks on the subcellular scale in clinical ion beams. The Cell-Fit-HD comprises a fluorescent nuclear track detector (FNTD, the physical compartment), a device for individual particle detection and a substrate for viable cell-coating, i.e. the biological compartment. To date both compartments have been imaged sequentially in situ by confocal laser scanning microscopy (CLSM). This is yet in conflict with a functional read-out of the Cell-Fit-HD utilizing a fast live-cell imaging of the biological compartment with low phototoxicity on greater time scales. The read-out of the biological from the physical compartment was uncoupled. A read-out procedure was developed to image the cell layer by conventional widefield microscopy whereas the FNTD was imaged by CLSM. Point mapping registration of the confocal and widefield imaging data was performed. Non-fluorescent crystal defects (spinels) visible in both read-outs were used as control point pairs. The accuracy achieved was on the sub-µm scale. The read-out procedure by widefield microscopy does not impair the unique ability of spatial correlation by the Cell-Fit-HD. The uncoupling will enlarge the application potential of the hybrid technology significantly. The registration allows for an ultimate correlation of microscopic physical beam parameters and cell kinetics on greater time scales. The method reported herein will be instrumental for the introduction of a novel generation of compact detectors facilitating biodosimetric research towards high-throughput analysis.

Fluence-based dosimetry of proton and heavier ion beams using single track detectors.

Due to their superior spatial resolution, small and biocompatible fluorescent nuclear track detectors (FNTDs) open up the possibility of characterizing swift heavy charged particle fields on a single track level. Permanently stored spectroscopic information such as energy deposition and particle field composition is of particular importance in heavy ion radiotherapy, since radiation quality is one of the decisive predictors for clinical outcome. Findings presented within this paper aim towards single track reconstruction and fluence-based dosimetry of proton and heavier ion fields. Three-dimensional information on individual ion trajectories through the detector volume is obtained using fully automated image processing software. Angular distributions of multidirectional fields can be measured accurately within ±2° uncertainty. This translates into less than 5% overall fluence deviation from the chosen irradiation reference. The combination of single ion tracking with an improved energy loss calibration curve based on 90 FNTD irradiations with protons as well as helium, carbon and oxygen ions enables spectroscopic analysis of a detector irradiated in Bragg peak proximity of a 270 MeV u(-1) carbon ion field. Fluence-based dosimetry results agree with treatment planning software reference.

Ion track reconstruction in 3D using alumina-based fluorescent nuclear track detectors.

Fluorescent nuclear track detectors (FNTDs) based on Al2O3: C, Mg single crystal combined with confocal microscopy provide 3D information on ion tracks with a resolution only limited by light diffraction. FNTDs are also ideal substrates to be coated with cells to engineer cell-fluorescent ion track hybrid detectors (Cell-Fit-HD). This radiobiological tool enables a novel platform linking cell responses to physical dose deposition on a sub-cellular level in proton and heavy ion therapies. To achieve spatial correlation between single ion hits in the cell coating and its biological response the ion traversals have to be reconstructed in 3D using the depth information gained by the FNTD read-out. FNTDs were coated with a confluent human lung adenocarcinoma epithelial (A549) cell layer. Carbon ion irradiation of the hybrid detector was performed perpendicular and angular to the detector surface. In situ imaging of the fluorescently labeled cell layer and the FNTD was performed in a sequential read-out. Making use of the trajectory information provided by the FNTD the accuracy of 3D track reconstruction of single particles traversing the hybrid detector was studied. The accuracy is strongly influenced by the irradiation angle and therefore by complexity of the FNTD signal. Perpendicular irradiation results in highest accuracy with error of smaller than 0.10°. The ability of FNTD technology to provide accurate 3D ion track reconstruction makes it a powerful tool for radiobiological investigations in clinical ion beams, either being used as a substrate to be coated with living tissue or being implanted in vivo.

The application of amorphous track models to study cell survival in heavy ions beams.

In a study of amorphous track models, in the local effect model (LEM), the Kellerer algorithm was used, which folds radial dose distributions from different ion tracks. In representative set of 10 experimental cell survival curves of normal human skin fibroblast cells irradiated with carbon ions, the method that applies the Kellerer algorithm was found to be more accurate and 10(4) times faster than the usual Monte Carlo summation method based on a regular grid.