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The interaction between gut microbiota and host plays a central role in health. Dysbiosis, detrimental changes in gut microbiota and inflammation have been reported in non-communicable diseases. While diet has a profound impact on gut microbiota composition and function, the role of food additives such as titanium dioxide (TiO 2 ), prevalent in processed food, is less established. In this project, we investigated the impact of food grade TiO 2 on gut microbiota of mice when orally administered via drinking water. While TiO 2 had minimal impact on the composition of the microbiota in the small intestine and colon, we found that TiO 2 treatment could alter the release of bacterial metabolites in vivo and affect the spatial distribution of commensal bacteria in vitro by promoting biofilm formation. We also found reduced expression of the colonic mucin 2 gene, a key component of the intestinal mucus layer, and increased expression of the beta defensin gene, indicating that TiO 2 significantly impacts gut homeostasis. These changes were associated with colonic inflammation, as shown by decreased crypt length, infiltration of CD8 + T cells, increased macrophages as well as increased expression of inflammatory cytokines. These findings collectively show that TiO 2 is not inert, but rather impairs gut homeostasis which may in turn prime the host for disease development.

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.

Microbeam radiation therapy is a novel pre-clinical external beam therapy that uses high-brilliance synchrotron X-rays to deliver the necessary high dose rates. The unique conditions of high dose rate and high spatial fractionation demand a new class of detector to experimentally measure important beam quality parameters. Here we demonstrate the highest spatial resolution plastic scintillator fibre-optic dosimeter found in the literature to date and tested it on the Imaging and Medical Beam-Line at the Australian Synchrotron in a X-ray beam where the irradiation dose rate was 4435 Gy/s. With a one-dimensional spatial resolution of 10 μ m the detector is able to resolve the individual microbeams (53.7 ± 0.4 μ m wide), and measure the peak-to-valley dose ratio to be 55 ± 17. We also investigate the role of radioluminescence in the optical fibre used to transport the scintillation photons, and conclude that it creates a significant contribution to the total light detected.

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.

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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.

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