Validation of a Monte Carlo simulation for Microbeam Radiation Therapy on the Imaging and Medical Beamline at the Australian Synchrotron.

Microbeam Radiation Therapy (MRT) is an emerging cancer treatment modality characterised by the use of high-intensity synchrotron-generated x-rays, spatially fractionated by a multi-slit collimator (MSC), to ablate target tumours. The implementation of an accurate treatment planning system, coupled with simulation tools that allow for independent verification of calculated dose distributions are required to ensure optimal treatment outcomes via reliable dose delivery. In this article we present data from the first Geant4 Monte Carlo radiation transport model of the Imaging and Medical Beamline at the Australian Synchrotron. We have developed the model for use as an independent verification tool for experiments in one of three MRT delivery rooms and therefore compare simulation results with equivalent experimental data. The normalised x-ray spectra produced by the Geant4 model and a previously validated analytical model, SPEC, showed very good agreement using wiggler magnetic field strengths of 2 and 3 T. However, the validity of absolute photon flux at the plane of the Phase Space File (PSF) for a fixed number of simulated electrons was unable to be established. This work shows a possible limitation of the G4SynchrotronRadiation process to model synchrotron radiation when using a variable magnetic field. To account for this limitation, experimentally derived normalisation factors for each wiggler field strength determined under reference conditions were implemented. Experimentally measured broadbeam and microbeam dose distributions within a Gammex RMI457 Solid Water® phantom were compared to simulated distributions generated by the Geant4 model. Simulated and measured broadbeam dose distributions agreed within 3% for all investigated configurations and measured depths. Agreement between the simulated and measured microbeam dose distributions agreed within 5% for all investigated configurations and measured depths.

Comparison of phantom materials for use in quality assurance of microbeam radiation therapy.

Microbeam radiation therapy (MRT) is a promising radiotherapy modality that uses arrays of spatially fractionated micrometre-sized beams of synchrotron radiation to irradiate tumours. Routine dosimetry quality assurance (QA) prior to treatment is necessary to identify any changes in beam condition from the treatment plan, and is undertaken using solid homogeneous phantoms. Solid phantoms are designed for, and routinely used in, megavoltage X-ray beam radiation therapy. These solid phantoms are not necessarily designed to be water-equivalent at low X-ray energies, and therefore may not be suitable for MRT QA. This work quantitatively determines the most appropriate solid phantom to use in dosimetric MRT QA. Simulated dose profiles of various phantom materials were compared with those calculated in water under the same conditions. The phantoms under consideration were RMI457 Solid Water (Gammex-RMI, Middleton, WI, USA), Plastic Water (CIRS, Norfolk, VA, USA), Plastic Water DT (CIRS, Norfolk, VA, USA), PAGAT (CIRS, Norfolk, VA, USA), RW3 Solid Phantom (PTW Freiburg, Freiburg, Germany), PMMA, Virtual Water (Med-Cal, Verona, WI, USA) and Perspex. RMI457 Solid Water and Virtual Water were found to be the best approximations for water in MRT dosimetry (within ±3% deviation in peak and 6% in valley). RW3 and Plastic Water DT approximate the relative dose distribution in water (within ±3% deviation in the peak and 5% in the valley). PAGAT, PMMA, Perspex and Plastic Water are not recommended to be used as phantoms for MRT QA, due to dosimetric discrepancies greater than 5%.

X-Tream quality assurance in synchrotron X-ray microbeam radiation therapy.

Microbeam radiation therapy (MRT) is a novel irradiation technique for brain tumours treatment currently under development at the European Synchrotron Radiation Facility in Grenoble, France. The technique is based on the spatial fractionation of a highly brilliant synchrotron X-ray beam into an array of microbeams using a multi-slit collimator (MSC). After promising pre-clinical results, veterinary trials have recently commenced requiring the need for dedicated quality assurance (QA) procedures. The quality of MRT treatment demands reproducible and precise spatial fractionation of the incoming synchrotron beam. The intensity profile of the microbeams must also be quickly and quantitatively characterized prior to each treatment for comparison with that used for input to the dose-planning calculations. The Centre for Medical Radiation Physics (University of Wollongong, Australia) has developed an X-ray treatment monitoring system (X-Tream) which incorporates a high-spatial-resolution silicon strip detector (SSD) specifically designed for MRT. In-air measurements of the horizontal profile of the intrinsic microbeam X-ray field in order to determine the relative intensity of each microbeam are presented, and the alignment of the MSC is also assessed. The results show that the SSD is able to resolve individual microbeams which therefore provides invaluable QA of the horizontal field size and microbeam number and shape. They also demonstrate that the SSD used in the X-Tream system is very sensitive to any small misalignment of the MSC. In order to allow as rapid QA as possible, a fast alignment procedure of the SSD based on X-ray imaging with a low-intensity low-energy beam has been developed and is presented in this publication.

High resolution 3D imaging of synchrotron generated microbeams.

PURPOSE: Microbeam radiation therapy (MRT) techniques are under investigation at synchrotrons worldwide. Favourable outcomes from animal and cell culture studies have proven the efficacy of MRT. The aim of MRT researchers currently is to progress to human clinical trials in the near future. The purpose of this study was to demonstrate the high resolution and 3D imaging of synchrotron generated microbeams in PRESAGE® dosimeters using laser fluorescence confocal microscopy. METHODS: Water equivalent PRESAGE® dosimeters were fabricated and irradiated with microbeams on the Imaging and Medical Beamline at the Australian Synchrotron. Microbeam arrays comprised of microbeams 25-50 µm wide with 200 or 400 µm peak-to-peak spacing were delivered as single, cross-fire, multidirectional, and interspersed arrays. Imaging of the dosimeters was performed using a nikon a1 laser fluorescence confocal microscope. RESULTS: The spatial fractionation of the MRT beams was clearly visible in 2D and up to 9 mm in depth. Individual microbeams were easily resolved with the full width at half maximum of microbeams measured on images with resolutions of as low as 0.09 µm/pixel. Profiles obtained demonstrated the change of the peak-to-valley dose ratio for interspersed MRT microbeam arrays and subtle variations in the sample positioning by the sample stage goniometer were measured. CONCLUSIONS: Laser fluorescence confocal microscopy of MRT irradiated PRESAGE® dosimeters has been validated in this study as a high resolution imaging tool for the independent spatial and geometrical verification of MRT beam delivery.

Energy spectra considerations for synchrotron radiotherapy trials on the ID17 bio-medical beamline at the European Synchrotron Radiation Facility.

The aim of this study was to validate the kilovoltage X-ray energy spectrum on the ID17 beamline at the European Synchrotron Radiation Facility (ESRF). The purpose of such validation was to provide an accurate energy spectrum as the input to a computerized treatment planning system, which will be used in synchrotron microbeam radiotherapy trials at the ESRF. Calculated and measured energy spectra on ID17 have been reported previously but recent additions and safety modifications to the beamline for veterinary trials warranted a fresh investigation. The authors used an established methodology to compare X-ray attenuation measurements in copper sheets (referred to as half value layer measurements in the radiotherapy field) with the predictions of a theoretical model. A cylindrical ionization chamber in air was used to record the relative attenuation of the X-ray beam intensity by increasing thicknesses of high-purity copper sheets. The authors measured the half value layers in copper for two beamline configurations, which corresponded to differing spectral conditions. The authors obtained good agreement between the measured and predicted half value layers for the two beamline configurations. The measured first half value layer was 1.754 ± 0.035 mm Cu and 1.962 ± 0.039 mm Cu for the two spectral conditions, compared with theoretical predictions of 1.763 ± 0.039 mm Cu and 1.984 ± 0.044 mm Cu, respectively. The calculated mean energies for the two conditions were 105 keV and 110 keV and there was not a substantial difference in the calculated percentage depth dose curves in water between the different spectral conditions. The authors observed a difference between their calculated energy spectra and the spectra previously reported by other authors, particularly at energies greater than 100 keV. The validation of the beam spectrum by the copper half value layer measurements means the authors can provide an accurate spectrum as an input to a treatment planning system for the forthcoming veterinary trials of microbeam radiotherapy to spontaneous tumours in cats and dogs.

Benchmarking and validation of a Geant4-SHADOW Monte Carlo simulation for dose calculations in microbeam radiation therapy.

Microbeam radiation therapy (MRT) is a synchrotron-based radiotherapy modality that uses high-intensity beams of spatially fractionated radiation to treat tumours. The rapid evolution of MRT towards clinical trials demands accurate treatment planning systems (TPS), as well as independent tools for the verification of TPS calculated dose distributions in order to ensure patient safety and treatment efficacy. Monte Carlo computer simulation represents the most accurate method of dose calculation in patient geometries and is best suited for the purpose of TPS verification. A Monte Carlo model of the ID17 biomedical beamline at the European Synchrotron Radiation Facility has been developed, including recent modifications, using the Geant4 Monte Carlo toolkit interfaced with the SHADOW X-ray optics and ray-tracing libraries. The code was benchmarked by simulating dose profiles in water-equivalent phantoms subject to irradiation by broad-beam (without spatial fractionation) and microbeam (with spatial fractionation) fields, and comparing against those calculated with a previous model of the beamline developed using the PENELOPE code. Validation against additional experimental dose profiles in water-equivalent phantoms subject to broad-beam irradiation was also performed. Good agreement between codes was observed, with the exception of out-of-field doses and toward the field edge for larger field sizes. Microbeam results showed good agreement between both codes and experimental results within uncertainties. Results of the experimental validation showed agreement for different beamline configurations. The asymmetry in the out-of-field dose profiles due to polarization effects was also investigated, yielding important information for the treatment planning process in MRT. This work represents an important step in the development of a Monte Carlo-based independent verification tool for treatment planning in MRT.

Method of Monte Carlo simulation verification in hadron therapy with non-tissue equivalent detectors.

In hadron therapy the spectra of secondary particles can be very broad in type and energy. The most accurate calculations of tissue equivalent (TE) absorbed dose and biological effect can be achieved using Monte Carlo (MC) simulations followed by the application of an appropriate radiobiological model. The verification of MC simulations is therefore an important quality assurance (QA) issue in dose planning. We propose a method of verification for MC dose calculations based on measurements of either the integral absorbed dose or the spectra of deposited energies from single secondary particles in non-TE material detectors embedded in a target of interest (phantom). This method was tested in boron neutron capture therapy and fast neutron therapy beams.

The role of nonelastic reactions in absorbed dose distributions from therapeutic proton beams in different medium.

Many new techniques for delivering radiation therapy are being developed for the treatment of cancer. One of these, proton therapy, is becoming increasingly popular because of the precise way in which protons deliver dose to the tumor volume. In order to achieve this level of precision, extensive treatment planning needs to be carried out to determine the optimum beam energies, energy spread (which determines the width of the spread-out Bragg peak), and angles for each patient's treatment. Due to the level of precision required and advancements in computer technology, there is increasing interest in the use of Monte Carlo calculations for treatment planning in proton therapy. However, in order to achieve optimum simulation times, nonelastic nuclear interactions between protons and the target nucleus within the patient's internal structure are often not accounted for or are simulated using less accurate models such as analytical or ray tracing. These interactions produce high LET particles such as neutrons, alpha particles, and recoil protons, which affect the dose distribution and biological effectiveness of the beam. This situation has prompted an investigation of the importance of nonelastic products on depth dose distributions within various materials including water, A-150 tissue equivalent plastic, ICRP (International Commission on Radiological Protection) muscle, ICRP bone, and ICRP adipose. This investigation was conducted utilizing the GEANT4.5.2 Monte Carlo hadron transport toolkit.