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

Higher Education and behavior analysis in Europe::Creating a unified approach for the training of autism professionals

Training of behaviour analysts for autism services, has improved notably within a European higher education context. However, regional discrepancies associated with economic, health care, social services, and institutional policies magnify the importance of creating appropriate unified training and consumer protection. Although the European Association for Behaviour Analysis (EABA) has endorsed the Behavior Analyst Certification Board’s (BACB) designations, the absence of European and national regulations, recognition, and accreditation remain significant barriers to quality training and implementation. These challenges are  particularly pertinent in light of BACB decision to limit certification to residents in the USA and Canada after 2022. Advances, challenges, and future directions are discussed within the context of higher education in the United Kingdom, the Czech Republic, Greece, Iceland, Italy, Norway, and Sweden. The post-Bologna European agenda for higher education, globalization and opportunities for the training of behaviour analysts within European higher education are outlined

Polo-like kinase 1 inhibitor BI6727 sensitizes 9L gliosarcoma cells to ionizing irradiation

Surgery, chemotherapy and radiotherapy remain as the major treatment strategies for cancers. Some agents such as anti-cancer drugs have capacity to enhance the radiation sensitivity of cancer cells at G2/M phase, leading to an improved radiotherapeutic efficacy. BI6727 is an ATP-competitive pololike kinase 1 (Plk 1)inhibitor and an anti-cancer drug. Using the radio-resistant 9L rat gliosarcoma cells as model, we examined the effect of BI6727 on cell growth and assessed the chemoradiotherapeutic efficiency between 150 kVp conventional irradiation (dose rate of 0.76 Gy min−1 ) and 66 keV synchrotron x-ray broad beam irradiation (dose rate of 46 Gy s−1). Our studies showed that BI6727 significantly caused cell growth arrest at G2/M phase and inhibited 9L cell proliferation with EC50 of 58.1 nM. In combinatory treatment, irradiation of BI6727-treated 9L cells with synchrotron x-rays at a dose rate of 46 Gy s−1 resulted in significant reduction of the cell survival compared to the conventional x-rays at a dose rate of 0.76 Gy min−1. These results indicated that Plk1 inhibitor BI6727 enhanced radio-sensitization of 9L cells in a dose rate dependent manner. For clinical application, irradiation with high dose rate is a promising strategy to improve chemo-radiotherapeutic efficacy for gliosarcoma cancer

Characterisation and evaluation of a PNP strip detector for synchrotron microbeam radiation therapy

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

New 3D Silicon detectors for dosimetry in Microbeam Radiation Therapy

Microbeam Radiation Therapy (MRT) involves the use of a spatially fractionated beam of synchrotron generated X-rays to treat tumours. MRT treatment is delivered via an array of high dose \u27peaks\u27 separated by low dose \u27valleys\u27. A good Peak to Valley Dose Ratio (PVDR) is an important indicator of successful treatment outcomes. MRT dosimetry requires a radiation hard detector with high spatial resolution, large dynamic range, which is ideally real-time and tissue equivalent. We have developed a Silicon Strip Detector (SSD) and very recently, a new 3D MESA SSD to meet the very stringent requirements of MRT dosimetry. We have compared these detectors through the characterisation of the MRT radiation field at the Australian Synchrotron Imaging and Medical Beamline. The EPI SSD was able to measure the microbeam profiles and PVDRs, however the effective spatial resolution was limited by the detector alignment options available at the time. The geometry of the new 3D MESA SSD is less sensitive to this alignment restriction was able to measure the microbeam profiles within 2 ¿m of that expected. The 3D MESA SSD measured PVDRs were possibly affected by undesired and slow charge collection outside the sensitive volume and additional scattering from the device substrate

X-ray microbeam measurements with a high resolution scintillator fibre-optic dosimeter

Synchrotron microbeam radiation therapy is a novel external beam therapy under investigation, that uses highly brilliant synchrotron x-rays in microbeams 50 μm width, with separation of 400 μm, as implemented here. Due to the fine spatial fractionation dosimetry of these beams is a challenging and complicated problem. In this proof-of-concept work, we present a fibre optic dosimeter that uses plastic scintillator as the radiation conversion material. We claim an ideal one-dimensional resolution of 50 μm. Using plastic scintillator and fibre optic makes this dosimeter water-equivalent, a very desirable dosimetric property. The dosimeter was tested at the Australian Synchrotron, on the Imaging and Medical Beam-Line. The individual microbeams were able to be resolved and the peak-to-valley dose ratio and the full width at half maximum of the microbeams was measured. These results are compared to a semiconductor strip detector of the same spatial resolution. A percent depth dose was measured and compared to data acquired by an ionisation chamber. The results presented demonstrate significant steps towards the development of an optical dosimeter with the potential to be applied in quality assurance of microbeam radiation therapy, which is vital if clinical trials are to be performed on human patients

X-Tream dosimetry of highly brilliant X-ray microbeams in the MRT hutch of the Australian Synchrotron

The X-Tream dosimetry system developed at the Centre for Medical Radiation Physics (University of Wollongong, Australia) utilises a high resolution silicon Single Strip Detector to characterise synchrotron radiation microbeams for the purpose of Quality Assurance of Microbeam Radiation Therapy. Firstly, a comparison of the Silicon Strip Detector performance with respect to a conventional PinPoint Ionisation Chamber for broad beams and microbeams is given. These results are then extended to characterise the horizontal microbeam radiation field available in the high flux experimental hutch of the Imaging and Medical BeamLine at the Australian Synchrotron. The Silicon Strip Detector measured depth dose curve of the broad beam agrees very well with the PinPoint Ionisation Chamber measurements between 10 and 50 mm depth in water. Significant deviations from the PinPoint Ionisation Chamber response are observed with increasing depth. Microbeam profiles measured by the Silicon Strip Detector are well resolved but clearly affected by misalignment of the Silicon Strip Detector with respect to the microbeams. Future beamline technical improvements will alleviate this issue

First experimental evaluation of multi-target multileaf collimator tracking during volumetric modulated arc therapy for locally advanced prostate cancer.

PURPOSE: Locally advanced and oligometastatic cancer patients require radiotherapy treatment to multiple independently moving targets. There is no existing commercial solution that can simultaneously track and treat multiple targets. This study experimentally implemented and evaluated a real-time multi-target tracking system for locally advanced prostate cancer. METHODS: Real-time multi-target MLC tracking was integrated with 3D x-ray image guidance on a standard linac. Three locally advanced prostate cancer treatment plans were delivered to a static lymph node phantom and dynamic prostate phantom that reproduced three prostate trajectories. Treatments were delivered using multi-target MLC tracking, single-target MLC tracking, and no tracking. Doses were measured using Gafchromic film placed in the dynamic and static phantoms. Dosimetric error was quantified by the 2%/2 mm gamma failure rate. Geometric error was evaluated as the misalignment between target and aperture positions. The multi-target tracking system latency was measured. RESULTS: The mean (range) gamma failure rates for the prostate and lymph nodes, were 18.6% (5.2%, 28.5%) and 7.5% (1.1%, 13.7%) with multi-target tracking, 7.9% (0.7%, 15.4%) and 37.8% (18.0%, 57.9%) with single-target tracking, and 38.1% (0.6%, 75.3%) and 37.2% (29%, 45.3%) without tracking. Multi-target tracking had the lowest geometric error with means and standard deviations within 0.2 ± 1.5 for the prostate and 0.0 ± 0.3 mm for the lymph nodes. The latency was 730 ± 20 ms. CONCLUSION: This study presented the first experimental implementation of multi-target tracking to independently track prostate and lymph node displacement during VMAT. Multi-target tracking reduced dosimetric and geometric errors compared to single-target tracking and no tracking

Toward personalized synchrotron microbeam radiation therapy

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 ground-breaking 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

Synchrotron X-ray microbeam dosimetry with a 20 micrometre resolution scintillator fibre-optic dosimeter

Cancer is one of the leading causes of death worldwide. External beam radiation therapy is one of the most important modalities for the treatment of cancers. Synchrotron microbeam radiation therapy (MRT) is a novel pre-clinical therapy that uses highly spatially fractionated X-ray beams to target tumours, allowing doses much higher than conventional radiotherapies to be delivered. A dosimeter with a high spatial resolution is required to provide the appropriate quality assurance for MRT. This work presents a plastic scintillator fibre optic dosimeter with a one-dimensional spatial resolution of 20 µm, an improvement on the dosimeter with a resolution of 50 µm that was demonstrated in previous work. The ability of this probe to resolve microbeams of width 50 µm has been demonstrated. The major limitations of this method were identified, most notably the low-light signal resulting from the small sensitive volume, which made valley dose measurements very challenging. A titanium-based reflective paint was used as a coating on the probe to improve the light collection, but a possible effect of the high-Z material on the probes water-equivalence has been identified. The effect of the reflective paint was a 28.5 ± 4.6% increase in the total light collected; it did not affect the shape of the depth-dose profile, nor did it explain an over-response observed when used to probe at low depths, when compared with an ionization chamber. With improvements to the data acquisition, this probe design has the potential to provide a water-equivalent, inexpensive dosimetry tool for MRT