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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. [ABSTRACT FROM AUTHOR]

The production of anthropomorphic phantoms generated from tissue-equivalent materials is challenging but offers an excellent copy of the typical environment encountered in typical patients. High-quality dosimetry measurements and the correlation of the measured dose with the biological effects elicited by it are a prerequisite in preparation of clinical trials with novel radiotherapy approaches. We designed and produced a partial upper arm phantom from tissue-equivalent materials for use in experimental high-dose-rate radiotherapy. The phantom was compared to original patient data using density values and Hounsfield units obtained from CT scans. Dose simulations were conducted for broad-beam irradiation and microbeam radiotherapy (MRT) and compared to values measured in a synchrotron radiation experiment. Finally, we validated the phantom in a pilot experiment with human primary melanoma cells. [ABSTRACT FROM AUTHOR]

Simple Summary: Organs which receive an irradiation dose because they are located in the vicinity of the irradiation target are considered organs of risk. Before a new irradiation technique is tested in clinical trials, it is important to make an assessment of the potential adverse effects in these organs of risk. Microbeam radiotherapy is an innovative radiotherapy technique suitable to control tumours which are considered radioresistant with conventional, already clinically established irradiation techniques. In a small animal model, we have conducted a risk assessment in the thoracic spinal cord as organ of risk during microbeam irradiation in the thoracic cavity and determined the upper dose limit beyond which neurological signs of temporary or permanent damage occur. Microbeam radiotherapy (MRT), a high dose rate radiotherapy technique using spatial dose fractionation at the micrometre range, has shown a high therapeutic efficacy in vivo in different tumour entities, including lung cancer. We have conducted a toxicity study for the spinal cord as organ of risk during irradiation of a target in the thoracic cavity. In young adult rats, the lower thoracic spinal cord was irradiated over a length of 2 cm with an array of quasi-parallel microbeams of 50 µm width, spaced at a centre-to-centre distance of 400 µm, with MRT peak doses up to 800 Gy. No acute or subacute adverse effects were observed within the first week after irradiation up to MRT peak doses of 400 Gy. No significant differences were seen between irradiated animals and non-irradiated controls in motor function and sensitivity, open field test and somatosensory evoked potentials (SSEP). After irradiation with MRT peak doses of 450–800 Gy, dose-dependent neurologic signs occurred. Provided that long-term studies do not reveal significant morbidity due to late toxicity, an MRT dose of 400 Gy can be considered safe for the spinal cord in the tested beam geometry and field size. [ABSTRACT FROM AUTHOR]

Simple Summary: This work describes the development of a fast and accurate machine learning (ML) 3D U-Net dose engine, trained with Monte Carlo (MC) radiation transport simulations, to calculate the dose in rat patients treated in Microbeam Radiation Therapy (MRT) preclinical studies at the Imaging and Medical Beamline at the Australian Synchrotron. Digital phantoms are created based on CT scans of sixteen rats and are augmented to obtain enough anatomical data. Augmented variations of the digital phantoms are then used to simulate with Geant4 the energy depositions of an MRT beam inside the phantoms with 15% (high-noise) and 2% (low-noise) statistical uncertainty. The high-noise MC simulations are used for ML model training and validation, while the low-noise ones for testing. The results show that the ML dose engine provides a satisfactory dose description in the tumor target and generates the dose maps in less than one second. Microbeam radiation therapy (MRT) utilizes coplanar synchrotron radiation beamlets and is a proposed treatment approach for several tumor diagnoses that currently have poor clinical treatment outcomes, such as gliosarcomas. Monte Carlo (MC) simulations are one of the most used methods at the Imaging and Medical Beamline, Australian Synchrotron to calculate the dose in MRT preclinical studies. The steep dose gradients associated with the 50 μ m-wide coplanar beamlets present a significant challenge for precise MC simulation of the dose deposition of an MRT irradiation treatment field in a short time frame. The long computation times inhibit the ability to perform dose optimization in treatment planning or apply online image-adaptive radiotherapy techniques to MRT. Much research has been conducted on fast dose estimation methods for clinically available treatments. However, such methods, including GPU Monte Carlo implementations and machine learning (ML) models, are unavailable for novel and emerging cancer radiotherapy options such as MRT. In this work, the successful application of a fast and accurate ML dose prediction model for a preclinical MRT rodent study is presented for the first time. The ML model predicts the peak doses in the path of the microbeams and the valley doses between them, delivered to the tumor target in rat patients. A CT imaging dataset is used to generate digital phantoms for each patient. Augmented variations of the digital phantoms are used to simulate with Geant4 the energy depositions of an MRT beam inside the phantoms with 15% (high-noise) and 2% (low-noise) statistical uncertainty. The high-noise MC simulation data are used to train the ML model to predict the energy depositions in the digital phantoms. The low-noise MC simulations data are used to test the predictive power of the ML model. The predictions of the ML model show an agreement within 3% with low-noise MC simulations for at least 77.6% of all predicted voxels (at least 95.9% of voxels containing tumor) in the case of the valley dose prediction and for at least 93.9% of all predicted voxels (100.0% of voxels containing tumor) in the case of the peak dose prediction. The successful use of high-noise MC simulations for the training, which are much faster to produce, accelerates the production of the training data of the ML model and encourages transfer of the ML model to different treatment modalities for other future applications in novel radiation cancer therapies. [ABSTRACT FROM AUTHOR]

Microbeam radiotherapy could help to cure malignant tumours which are currently still considered therapy-resistant. With an irradiation target in the thoracic cavity, the heart would be one of the most important organs at risk. To assess the acute adverse effects of microbeam irradiation in the heart, a powerful ex vivo tool was created by combining the Langendorff model of the isolated beating mammalian heart with X-Tream dosimetry. In a first pilot experiment conducted at the Biomedical and Imaging Beamline of the Australian Synchrotron, the system was tested at a microbeam peak dose approximately ten times higher than the anticipated future microbeam irradiation treatment doses. The entire heart was irradiated with a dose of 4000 Gy at a dose rate of >6000 Gy s'1, using an array of 50 mm-wide microbeams spaced at a centre-tocentre distance of 400 mm. Although temporary arrhythmias were seen, they reverted spontaneously to a stable rhythm and no cardiac arrest occurred. This amazing preservation of cardiac function is promising for future therapeutic approaches. [ABSTRACT FROM AUTHOR]

Purpose: 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 in multiple dimensions. The computing time for a single prediction is reduced from several hundred hours using Geant4 simulation to less than a second using the GAN model. Conclusions: The proposed GAN model predicts dose distributions inside unknown phantoms with only small deviations from the full MC simulation with computations times of less than a second. It demonstrates good interpolation ability to unseen but similar phantom geometries and is flexible enough to be trained on data with different radiation scenarios without the need for optimization of the model parameter. This proof‐of‐concept encourages to apply and further develop the model for the use in MRT treatment planning, which requires fast and accurate predictions with sub‐mm resolutions. [ABSTRACT FROM AUTHOR]

Successful transition of synchrotron‐based microbeam radiation therapy (MRT) from pre‐clinical animal studies to human trials is dependent upon ensuring that there are sufficient and adequate measures in place for quality assurance purposes. Transmission detectors provide researchers and clinicians with a real‐time quality assurance and beam‐monitoring instrument to ensure safe and accurate dose delivery. In this work, the effect of transmission detectors of different thicknesses (10 and 375 µm) upon the photon energy spectra and dose deposition of spatially fractionated synchrotron radiation is quantified experimentally and by means of a dedicated Geant4 simulation study. The simulation and experimental results confirm that the presence of the 375 µm thick transmission detector results in an approximately 1–6% decrease in broad‐beam and microbeam peak dose. The capability to account for the reduction in dose and change to the peak‐to‐valley dose ratio justifies the use of transmission detectors as thick as 375 µm in MRT provided that treatment planning systems are able to account for their presence. The simulation and experimental results confirm that the presence of the 10 µm thick transmission detector shows a negligible impact (<0.5%) on the photon energy spectra, dose delivery and microbeam structure for both broad‐beam and microbeam cases. Whilst the use of 375 µm thick detectors would certainly be appropriate, based upon the idea of best practice the authors recommend that 10 µm thick transmission detectors of this sort be utilized as a real‐time quality assurance and beam‐monitoring tool during MRT. [ABSTRACT FROM AUTHOR]

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 1.39 c Gy and a planar radiograh dose of less than 0.03 c Gy. Experimental validation of alignment accuracy with radiographic film demonstrates end to end accuracy of less than ± 0.34 m m 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 cm2 to a 0.5 × 0.5 cm2 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 cm2 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 cm2 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. [ABSTRACT FROM AUTHOR]

Ion Beam Induced Charge (IBIC) microscopy performed using highly tuned microbeams of accelerated ions with energies in the MeV range is the powerful tool for analysis of charge carrier transport properties in semiconductor devices based on semiconductor hetero-junction, metal-on-semiconductor and semiconductor-on-insulator configurations. Here we present two cases of recent applications of the IBIC microscopy in the field of medical radiation physics. The reduced-rate ion microbeams with energies in the MeV range and sub-micrometer spot-sizes have been used for the investigations of the charge collection efficiency (CCE) in sensitive volumes of segmented radiation detectors in order to measure the spatial distribution and uniformity of CCE in different polarization conditions. This information allows the determination of the charge carrier transport properties in selected substructures of a particular device and to quantify its ability to accurately determine the energy deposited by incident ionizing radiation - two fundamental requirements of any microdosimeter or detector of ionizing radiation. [ABSTRACT FROM AUTHOR]

Objective. This study aims to design, manufacture, and test 3D printed quality assurance (QA) dosimetry phantoms for synchrotron brain cancer radiation therapy at the Australian synchrotron. Approach. Fabricated 3D printed phantoms from simple slab phantoms, a preclinical rat phantom, and an anthropomorphic head phantom were fabricated and characterized. Attenuation measurements of various polymers, ceramics and metals were acquired using synchrotron monochromatic micro-computed tomography (CT) imaging. Polylactic acid plus, VeroClear, Durable resin, and tricalcium phosphate were used in constructing the phantoms. Furthermore, 3D printed bone equivalent materials were compared relative to ICRU bone and hemihydrate plaster. Homogeneous and heterogeneous rat phantoms were designed and fabricated using tissue-equivalent materials. Geometric accuracy, CT imaging, and consistency were considered. Moreover, synchrotron broad-beam x-rays were delivered using a 3 Tesla superconducting multipole wiggler field for four sets of synchrotron radiation beam qualities. Dose measurements were acquired using a PinPoint ionization chamber and compared relative to a water phantom and a RMI457 Solid Water phantom. Experimental depth doses were compared relative to calculated doses using a Geant4 Monte Carlo simulation. Main results. Polylactic acid (PLA+) shows to have a good match with the attenuation coefficient of ICRU water, while both tricalcium phosphate and hydroxyapatite have good attenuation similarity with ICRU bone cortical. PLA+ material can be used as substitute to RMI457 slabs for reference dosimetry with a maximum difference of 1.84%. Percent depth dose measurement also shows that PLA+ has the best match with water and RMI457 within ±2.2% and ±1.6%, respectively. Overall, PLA+ phantoms match with RMI457 phantoms within ±3%. Significance and conclusion. The fabricated phantoms are excellent tissue equivalent equipment for synchrotron radiation dosimetry QA measurement. Both the rat and the anthropomorphic head phantoms are useful in synchrotron brain cancer radiotherapy dosimetry, experiments, and future clinical translation of synchrotron radiotherapy and imaging., (Creative Commons Attribution license.)

Objective. This study aims to characterize radiological properties of selected additive manufacturing (AM) materials utilizing both material extrusion and vat photopolymerization technologies. Monochromatic synchrotron x-ray images and synchrotron treatment beam dosimetry were acquired at the hutch 3B and 2B of the Australian Synchrotron-Imaging and Medical Beamline. Approach. Eight energies from 30 keV up to 65 keV were used to acquire the attenuation coefficients of the AM materials. Comparison of theoretical, and experimental attenuation data of AM materials and standard solid water for MV linac was performed. Broad-beam dosimetry experiment through attenuated dose measurement and a Geant4 Monte Carlo simulation were done for the studied materials to investigate its attenuation properties specific for a 4 tesla wiggler field with varying synchrotron radiation beam qualities. Main results. Polylactic acid (PLA) plus matches attenuation coefficients of both soft tissue and brain tissue, while acrylonitrile butadiene styrene, Acrylonitrile styrene acrylate, and Draft resin have close equivalence to adipose tissue. Lastly, PLA, co-polyester plus, thermoplastic polyurethane, and White resins are promising substitute materials for breast tissue. For broad-beam experiment and simulation, many of the studied materials were able to simulate RMI457 Solid Water and bolus within ±10% for the three synchrotron beam qualities. These results are useful in fabricating phantoms for synchrotron and other related medical radiation applications such as orthovoltage treatments. Significance and conclusion. These 3D printing materials were studied as potential substitutes for selected tissues such as breast tissue, adipose tissue, soft-tissue, and brain tissue useful in fabricating 3D printed phantoms for synchrotron imaging, therapy, and orthovoltage applications. Fabricating customizable heterogeneous anthropomorphic phantoms (e.g. breast, head, thorax) and pre-clinical animal phantoms (e.g. rodents, canine) for synchrotron imaging and radiotherapy using AM can be done based on the results of this study., (Creative Commons Attribution license.)