Synchrotron facilities produce ultra-high dose rate X-rays that can be used for selective cancer treatment when combined with micron-sized beams. Synchrotron microbeam radiation therapy (MRT) has been shown to inhibit cancer growth in small animals, whilst preserving healthy tissue function. However, the underlying mechanisms that produce successful MRT outcomes are not well understood, either in vitro or in vivo. this study provides new insights into the relationships between dosimetry, radiation transport simulations, in vitro cell response, and pre-clinical brain cancer survival using intracerebral gliosarcoma (9LGS) bearing rats. As part of this groundbreaking research, a new image-guided MRT technique was implemented for accurate tumor targeting combined with a pioneering assessment of tumor dose-coverage; an essential parameter for clinical radiotherapy. Based on the results of our study, we can now (for the first time) present clear and reproducible relationships between the in vitro cell response, tumor dose-volume coverage and survival post MRT irradiation of an aggressive and radioresistant brain cancer in a rodent model. our innovative and interdisciplinary approach is illustrated by the results of the first long-term MRT pre-clinical trial in Australia. Implementing personalized synchrotron MRT for brain cancer treatment will advance this international research effort towards clinical trials.

Purpose: The PTW microDiamond has an enhanced spatial resolution when operated in an edge-on orientation but is not typically utilized in this orientation due to the specifications of the IAEA TRS-483 code of practice for small field dosimetry. In this work the suitability of an edge-on orientation and advantages over the recommended face-on orientation will be presented. Methods: The PTW microDiamond in both orientations was compared on a Varian TrueBeam linac for: machine output factor (OF), percentage depth dose (PDD), and beam profile measurements from 10 × 10 cm 2 to a 0.5 × 0.5 cm 2 field size for 6X and 6FFF beam energies in a water tank. A quantification of the stem effect was performed in edge-on orientation along with tissue to phantom ratio (TPR) measurements. An extensive angular dependence study for the two orientations was also undertaken within two custom PMMA plastic cylindrical phantoms. Results: The OF of the PTW microDiamond in both orientations agrees within 1% down to the 2 × 2 cm 2 field size. The edge-on orientation overresponds in the build-up region but provides improved penumbra and has a maximum observed stem effect of 1%. In the edge-on orientation there is an angular independent response with a maximum of 2% variation down to a 2 × 2 cm 2 field. The PTW microDiamond in edge-on orientation for TPR measurements agreed to the CC01 ionization chamber within 1% for all field sizes. Conclusions: The microDiamond was shown to be suitable for small field dosimetry when operated in edge-on orientation. When edge-on, a significantly reduced angular dependence is observed with no significant stem effect, making it a more versatile QA instrument for rotational delivery techniques.

Novel radiotherapy techniques like synchrotron X-ray microbeam radiation therapy (MRT) require fast dose distribution predictions that are accurate at the sub-mm level, especially close to tissue/bone/air interfaces. Monte Carlo (MC) physics simulations are recognized to be one of the most accurate tools to predict the dose delivered in a target tissue but can be very time consuming and therefore prohibitive for treatment planning. Faster dose prediction algorithms are usually developed for clinically deployed treatments only. In this work, we explore a new approach for fast and accurate dose estimations suitable for novel treatments using digital phantoms used in preclinical development and modern machine learning techniques. We develop a generative adversarial network (GAN) model, which is able to emulate the equivalent Geant4 MC simulation with adequate accuracy and use it to predict the radiation dose delivered by a broad synchrotron beam to various phantoms. Methods: The energy depositions used for the training of the GAN are obtained using full Geant4 MC simulations of a synchrotron radiation broad beam passing through the phantoms. The energy deposition is scored and predicted in voxel matrices of size 140 × 18 × 18 with a voxel edge length of 1 mm. The GAN model consists of two competing 3D convolutional neural networks, which are conditioned on the photon beam and phantom properties. The generator network has a U-Net structure and is designed to predict the energy depositions of the photon beam inside three phantoms of variable geometry with increasing complexity. The critic network is a relatively simple convolutional network, which is trained to distinguish energy depositions predicted by the generator from the ones obtained with the full MC simulation. Results: The energy deposition predictions inside all phantom geometries under investigation show deviations of less than 3% of the maximum deposited energy from the simulation for roughly 99% of the voxels in the field of the beam. Inside the most realistic phantom, a simple pediatric head, the model predictions deviate by less than 1% of the maximal energy deposition from the simulations in more than 96% of the in-field voxels. For all three phantoms, the model generalizes the energy deposition predictions well to phantom geometries,which have not been used for training the model but are interpolations of the training data inThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

The Quality Assurance requirements of detectors for Synchrotron Micro-beam Radiation Therapy are such that there are limited commercial systems available. The high intensity and spatial fractionation of synchrotron microbeams requires detectors be radiation hard and capable of measuring high dose gradients with high spatial resolution sensitivity. Silicon single strip detectors are a promising candidate for such applications. The PNP strip detector is an alternative design of an already proven technology and is assessed on its contextual viability. In this study, the electrical and charge collection efficiency properties of the device are characterised. In addition, a dedicated TCAD model is used to support ion beam induced charge measurements to determine the spatial resolution of the detector. Lastly, the detector was used to measure the full width half maximum and peak to valley dose ratio for microbeams with only a slight over response. With the exception of radiation hardness the PNP detector is a promising candidate for quality assurance in microbeam radiation therapy.

In this study, we demonstrate that the X-Tream dosimetry system developed by the Centre for Medical Radiation Physics can be used with both commercial and non-commercial dosimeters. A custom adaptor was constructed to connect the PTW microdiamond to the X-Tream DAQ. This allowed for the measurements of continuous depth dose curves, broad beam and microbeam profiles. The X-Tream system enables real time measurement of the instantaneous dose rate of synchrotron generated radiation with the PTW microDiamond. Finally, measurements undertaken in this study demonstrate that the X-Tream system is able to mitigate the alignment issue that has previously hampered the uptake of the PTW microdiamond in clinical quality assurance for small field dosimetry.

Synchrotron microbeam radiation therapy is a promising pre-clinical radiation treatment modality; however, it comes with many technical challenges. This study describes the image guidance protocol used for Australia’s first long-term pre-clinical MRT treatment of rats bearing 9L gliosarcoma tumours. The protocol utilises existing infrastructure available at the Australian Synchrotron and the adjoining Monash Biomedical Imaging facility. The protocol is designed and optimised to treat small animals utilising high-resolution clinical CT for patient specific tumour identification, coupled with conventional radiography, using the recently developed SyncMRT program for image guidance. Dosimetry performed in small animal phantoms shows patient dose is comparable to standard clinical doses, with a CT associated dose of less than 1.39cGy and a planar radiograh dose of less than 0.03cGy. Experimental validation of alignment accuracy with radiographic film demonstrates end to end accuracy of less than ±0.34mm in anatomical phantoms. Histological analysis of tumour-bearing rats treated with microbeam radiation therapy verifies that tumours are targeted well within applied treatment margins. To date, this technique has been used to treat 35 tumour-bearing rats.

Spatially fractionated ultra-high-dose-rate beams used during microbeam radiation therapy (MRT) have been shown to increase the differential response between normal and tumour tissue. Quality assurance of MRT requires a dosimeter that possesses tissue equivalence, high radiation tolerance and spatial resolution. This is currently an unsolved challenge. This work explored the use of a 500 nm thick organic semiconductor for MRT dosimetry on the Imaging and Medical Beamline at the Australian Synchrotron. Three beam filters were used to irradiate the device with peak energies of 48, 76 and 88 keV with respective dose rates of 3668, 500 and 209 Gy s−1. The response of the device stabilized to 30% efficiency after an irradiation dose of 30 kGy, with a 0.5% variation at doses of 35 kGy and higher. The calibration factor after pre-irradiation was determined to be 1.02 ± 0.005 µGy per count across all three X-ray energy spectra, demonstrating the unique advantage of using tissue-equivalent materials for dosimetry. The percentage depth dose curve was within ±5% of the PTW microDiamond detector. The broad beam was fractionated into 50 microbeams (50 µm FHWM and 400 µm centre-to-centre distance). For each beam filter, the FWHMs of all 50 microbeams were measured to be 51 ± 1.4, 53 ± 1.4 and 69 ± 1.9 µm, for the highest to lowest dose rate, respectively. The variation in response suggested the photodetector possessed dose-rate dependence. However, its ability to reconstruct the microbeam profile was affected by the presence of additional dose peaks adjacent to the one generated by the X-ray microbeam. Geant4 simulations proved that the additional peaks were due to optical photons generated in the barrier film coupled to the sensitive volume. The simulations also confirmed that the amplitude of the additional peak in comparison with the microbeam decreased for spectra with lower peak energies, as observed in the experimental data. The material packaging can be optimized during fabrication by solution processing onto a flexible substrate with a non-fluorescent barrier film. With these improvements, organic photodetectors show promising prospects as a cost-effective high spatial resolution tissue-equivalent flexible dosimeter for synchrotron radiation fields.

Recommendations for an experimental protocol for beam alignment/optimization and dosimetry relating to in vitro studies at the Imaging and Medical Beam Line of the Australian Synchrotron are presented. An evaluation of the protocol, based upon the consistency and reproducibility of in vitro experiments performed over several years at the Australian Synchrotron, is provided for the community.