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

Study of the X-ray radiation interaction with a multislit collimator for the creation of microbeams in radiation therapy

Microbeam radiation therapy (MRT) is a developing radiotherapy, based on the use of beams only a few tens of micrometres wide, generated by synchrotron X-ray sources. The spatial fractionation of the homogeneous beam into an array of microbeams is possible using a multislit collimator (MSC), i.e. a machined metal block with regular apertures. Dosimetry in MRT is challenging and previous works still show differences between calculated and experimental dose profiles of 10-30%, which are not acceptable for a clinical implementation of treatment. The interaction of the X-rays with the MSC may contribute to the observed discrepancies; the present study therefore investigates the dose contribution due to radiation interaction with the MSC inner walls and radiation leakage of the MSC. Dose distributions inside a water-equivalent phantom were evaluated for different field sizes and three typical spectra used for MRT studies at the European Synchrotron Biomedical beamline ID17. Film dosimetry was utilized to determine the contribution of radiation interaction with the MSC inner walls; Monte Carlo simulations were implemented to calculate the radiation leakage contribution. Both factors turned out to be relevant for the dose deposition, especially for small fields. Photons interacting with the MSC walls may bring up to 16% more dose in the valley regions, between the microbeams. Depending on the chosen spectrum, the radiation leakage close to the phantom surface can contribute up to 50% of the valley dose for a 5 mm × 5 mm field. The current study underlines that a detailed characterization of the MSC must be performed systematically and accurate MRT dosimetry protocols must include the contribution of radiation leakage and radiation interaction with the MSC in order to avoid significant errors in the dose evaluation at the micrometric scale

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

Validation of Geant4-based Simulation and Characterisation of Silicon Dosimeters for Quality Assurance and Beam Monitoring in Microbeam Radiation Therapy

Despite extensive research into improvements in brain cancer treatment, the cancer re- lated mortality since 1983 has remained nearly constant. Synchrotron-based radiotherapy microbeam radiation therapy (MRT) has emerged as a promising novel treatment aimed at improving tumour control while reducing normal tissue toxicities in brain cancer pa- tients. The complex features of the synchrotron source and microbeam (MB) array re- quires careful consideration in the quest towards the progression of MRT to clinical trials. The research presented in this PhD thesis aims contributes to the international field of re- search through advances in MRT quality assurance (QA) processes relating to treatment planning, dosimetry and treatment delivery verification. Specifically, this thesis evalu- ates an independent Geant4 Treatment Planning System (TPS) verification tool, a novel p-type epitaxial silicon strip detector, and finally the transmission characteristics of two silicon–based multi-strip detectors for transmission–based real-time beam monitoring in MRT. One major outcome is the development and implementation of the first exclusive Geant4 Monte Carlo model of the Imaging and Medical Beamline (IMBL) at the Australian Syn- chrotron (AS). This model was successfully validated experimentally, with agreement between simulated and measured broadbeam (BB) and microbeam (MB) dose distribu- tions within 3% and 5% respectively for all investigated configurations and measure- ment depths. Through this development, the research identified a potential limitation in the G4SynchrotronRadiation process when modelling the synchrotron radiation pro- duction in variable magnetic fields. Correction factors are necessary to account for the synchrotron radiation production modelling limitations in key MRT beamline configura- tions. The novel p-type epitaxial silicon strip detector demonstrates desirable detector characteristics for implementation in high resolution MRT dosimetry. Notable improve- ments, over a previous generation device, include improvement in the energy dependence (relative to water) and spatial resolution. The improvements in detector design pioneer a method for developing accurate silicon-based dosimetry for application in routine MRT QA. Suitable implementation enables pre-clinical trials and future clinical trials. Further work investigates the impact of a novel back-etched silicon–based multi-strip beam mon- itor on the MRT beam quality and dose deposition characteristics. Evaluated by means of Monte Carlo simulation and experimental methods, recommendations are made for implementing and modelling silicon–based beam monitors within the context of a future TPS

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

Silicon strip detector for quality assurance in synchrotron microbeam radiation therapy

Abstract of an oral communication that presented at the 53es Journées Scientifiques de la Société Française de Physique Médicale, 4-6 June 2014, Deauville, France

Silicon strip detector for quality assurance in synchrotron microbeam radiation therapy

Abstract of an oral communication that presented at the 53es Journées Scientifiques de la Société Française de Physique Médicale, 4-6 June 2014, Deauville, France