Young's double-slit interference with single hard X-ray photons.

Double-slit interference experiments using monochromatic hard X-rays with the energy of 25 keV are presented. The experiments were performed at a synchrotron source with a distance of 110 m between the interferometer and the detector to produce an interference pattern with a sufficiently broad period that could be adequately sampled by a photon-counting detector with 75 micrometre pixels. In the single-particle version of the experiment, over one million image frames with a single registered photon in each one were collected. The sum of these frames showed a clear presence of the interference pattern with the expected period. Subsequent analysis provided an objective estimation of the minimal number of detected photons required to determine, in accordance with the Rose criterion, the presence of the photon interference. Apart from a general theoretical interest, these investigations were aimed at exploring the possibility of medical X-ray phase-contrast imaging in photon-counting regime at minimal radiation doses.

Application of End-Tidal CO2 Monitoring to ICU Management.

Waveform capnography is a noninvasive measurement of ventilation and perfusion commonly employed in the prehospital setting. It is easy to apply, and modern cardiac monitors are equipped with the necessary ports and capability to display results. Despite its ease of use, end-tidal CO2 monitoring has not yet achieved widespread adoption within the hospital setting. It is routinely used in the emergency department and by anesthesiologists, but its application could support ICU management in critically ill patients. Its use is routinely supported by multiple professional societies, and it has been recommended as a requirement in all cardiac arrests. Careful analysis of the waveform and expired carbon dioxide can guide therapy for patients experiencing respiratory emergencies, hemodynamic compromise, metabolic acidosis, and shock due to trauma, hypovolemia, or sepsis. Use of capnography throughout the hospital could improve patient outcomes and prevent unidentified deterioration.

Genetic control of grain amino acid composition in a UK soft wheat mapping population.

Wheat (Triticum aestivum L.) is a major source of nutrients for populations across the globe, but the amino acid composition of wheat grain does not provide optimal nutrition. The nutritional value of wheat grain is limited by low concentrations of lysine (the most limiting essential amino acid) and high concentrations of free asparagine (precursor to the processing contaminant acrylamide). There are currently few available solutions for asparagine reduction and lysine biofortification through breeding. In this study, we investigated the genetic architecture controlling grain free amino acid composition and its relationship to other traits in a Robigus × Claire doubled haploid population. Multivariate analysis of amino acids and other traits showed that the two groups are largely independent of one another, with the largest effect on amino acids being from the environment. Linkage analysis of the population allowed identification of quantitative trait loci (QTL) controlling free amino acids and other traits, and this was compared against genomic prediction methods. Following identification of a QTL controlling free lysine content, wheat pangenome resources facilitated analysis of candidate genes in this region of the genome. These findings can be used to select appropriate strategies for lysine biofortification and free asparagine reduction in wheat breeding programs.

Effects of synchrotron-based X-rays and gold nanoparticles on normal and cancer cell morphology and migration.

It has been shown lately that gold nanoparticles (AuNPs) and ionizing radiation (IR) have inhibitory effects on cancer cell migration while having promoting effects on normal cells' motility. Also, IR increases cancer cell adhesion with no significant effects on normal cells. In this study, synchrotron-based microbeam radiation therapy, as a novel pre-clinical radiotherapy protocol, is employed to investigate the effects of AuNPs on cell migration. Experiments were conducted utilizing synchrotron X-rays to investigate cancer and normal cell morphology and migration behaviour when they are exposed to synchrotron broad beams (SBB) and synchrotron microbeams (SMB). This in vitro study was conducted in two phases. In phase I two cancer cell lines - human prostate (DU145) and human lung (A549) - were exposed to various doses of SBB and SMB. Based on the phase I results, in phase II two normal cell lines were studied: human epidermal melanocytes (HEM) and human primary colon epithelial (CCD841), along with their respective cancerous counterparts, human primary melanoma (MM418-C1) and human colorectal adenocarcinoma (SW48). The results show that radiation-induced damage in cells' morphology becomes visible with SBB at doses greater than 50 Gy, and incorporating AuNPs increases this effect. Interestly, under the same conditions, no visible morphological changes were observed in the normal cell lines post-irradiation (HEM and CCD841). This can be attributed to the differences in cell metabolic and reactive oxygen species levels between normal and cancer cells. The outcome of this study highlights future applications of synchrotron-based radiotherapy, where it is possible to deliver extremely high doses to cancer tissues whilst preserving surrounding normal tissues from radiation-induced damage.

Reducing Dietary Acrylamide Exposure from Wheat Products through Crop Management and Imaging.

The nutritional safety of wheat-based food products is compromised by the presence of the processing contaminant acrylamide. Reduction of the key acrylamide precursor, free (soluble, non-protein) asparagine, in wheat grain can be achieved through crop management strategies, but such strategies have not been fully developed. We ran two field trials with 12 soft (biscuit) wheat varieties and different nitrogen, sulfur, potassium, and phosphorus fertilizer combinations. Our results indicated that a nitrogen-to-sulfur ratio of 10:1 kg/ha was sufficient to prevent large increases in free asparagine, whereas withholding potassium or phosphorus alone did not cause increases in free asparagine when sulfur was applied. Multispectral measurements of plants in the field were able to predict the free asparagine content of grain with an accuracy of 71%, while a combination of multispectral, fluorescence, and morphological measurements of seeds could distinguish high free asparagine grain from low free asparagine grain with an accuracy of 86%. The acrylamide content of biscuits correlated strongly with free asparagine content and with color measurements, indicating that agronomic strategies to decrease free asparagine would be effective and that quality control checks based on product color could eliminate high acrylamide biscuit products.

Full Field X-Ray Scatter Tomography.

In X-ray imaging, photons are transmitted through and absorbed by the target object, but are also scattered in significant quantities. Previous attempts to use scattered X-ray photons for imaging applications used pencil or fan beam illumination. Here we present 3D X-ray Scatter Tomography using full-field illumination for small-animal imaging. Synchrotron imaging experiments were performed on a phantom and the chest of a juvenile rat. Transmitted and scattered photons were simultaneously imaged with separate cameras; a scientific camera directly downstream of the sample stage, and a pixelated detector with a pinhole imaging system placed at 45° to the beam axis. We obtained scatter tomogram feature fidelity sufficient for segmentation of the lungs and major airways in the rat. The image contrast in the scatter tomogram slices approached that of transmission imaging, indicating robustness to the amount of multiple scattering present in our case. This opens the possibility of augmenting full-field 2D imaging systems with additional scatter detectors to obtain complementary modes or to improve the fidelity of existing images without additional dose, potentially leading to single-shot or reduced-angle tomography or overall dose reduction for live animal studies.

Synchrotron X-Ray Radiation-Induced Bystander Effect: An Impact of the Scattered Radiation, Distance From the Irradiated Site and p53 Cell Status.

Synchrotron radiation, especially microbeam radiotherapy (MRT), has a great potential to improve cancer radiotherapy, but non-targeted effects of synchrotron radiation have not yet been sufficiently explored. We have previously demonstrated that scattered synchrotron radiation induces measurable γ-H2AX foci, a biomarker of DNA double-strand breaks, at biologically relevant distances from the irradiated field that could contribute to the apparent accumulation of bystander DNA damage detected in cells and tissues outside of the irradiated area. Here, we quantified an impact of scattered radiation to DNA damage response in "naïve" cells sharing the medium with the cells that were exposed to synchrotron radiation. To understand the effect of genetic alterations in naïve cells, we utilised p53-null and p53-wild-type human colon cancer cells HCT116. The cells were grown in two-well chamber slides, with only one of nine zones (of equal area) of one well irradiated with broad beam or MRT. γ-H2AX foci per cell values induced by scattered radiation in selected zones of the unirradiated well were compared to the commensurate values from selected zones in the irradiated well, with matching distances from the irradiated zone. Scattered radiation highly impacted the DNA damage response in both wells and a pronounced distance-independent bystander DNA damage was generated by broad-beam irradiations, while MRT-generated bystander response was negligible. For p53-null cells, a trend for a reduced response to scattered irradiation was observed, but not to bystander signalling. These results will be taken into account for the assessment of genotoxic effects in surrounding non-targeted tissues in preclinical experiments designed to optimise conditions for clinical MRT and for cancer treatment in patients.

Influence of the incubation temperature and total dissolved solids concentration on the biofilm and spore formation of dairy isolates of Geobacillus stearothermophilus.

Geobacillus species are an important contaminant in the dairy industry and their presence is often considered as an indicator of poor plant hygiene with the potential to cause spoilage. They can form heat resistant spores that adhere to surfaces of processing equipment and germinate to form biofilms. Therefore, strategies aimed towards preventing or controlling biofilm formation in the dairy industry are desirable. In this study we demonstrate that the preferred temperature for biofilm and spore formation among Geobacillus stearothermophilus A1, D1, P3 and ATCC 12980 was 65°C. Increasing the total dissolved milk solids concentration to 20% (w/v) caused an apparent delay in the onset of biofilm and spore formation to detectable concentrations among all the strains at 55°C. Compared to the onset time of the biofilm formation of A1 in 10% (w/v) reconstituted skim milk, addition of milk protein (whey protein and sodium caseinate) caused an apparent delay in the onset of biofilm formation to detectable concentrations by an average of 10 h at 55°C. This study proposes that temperature and total dissolved solids concentration have a cumulative effect on the biofilm and spore formation of G. stearothermophilus A1, D1, P3 and ATCC 12980. In addition, the findings from this study may indicate that preconditioning of stainless-steel surface with adsorbed milk proteins may delay the onset of biofilm and spore formation of thermophilic bacteria during milk powder manufacture.IMPORTANCE The thermophilic bacilli, Geobacillus stearothermophilus is a predominant spoilage bacterium in milk powder manufacturing plants. If their numbers exceed the accepted levels, this may incur financial loses by lowering the price of the end product. Furthermore, they can form heat resistant spores which adhere to processing surfaces and can germinate to form biofilms. Previously conducted research had highlighted the variation in the spore and biofilm formation among three specific strains of G. stearothermophilus isolated from a milk powder manufacturing plant in New Zealand. The significance of our research is demonstrating the effect of two abiotic factors namely temperature and total dissolved solids concentration on the biofilm and spore formation of these three dairy isolates, leading to modifications in the thermal processing steps aimed towards controlling the biofilm and spore formation of G. stearothermophilus in the dairy industry.

Methods for dynamic synchrotron X-ray respiratory imaging in live animals.

Small-animal physiology studies are typically complicated, but the level of complexity is greatly increased when performing live-animal X-ray imaging studies at synchrotron and compact light sources. This group has extensive experience in these types of studies at the SPring-8 and Australian synchrotrons, as well as the Munich Compact Light Source. These experimental settings produce unique challenges. Experiments are always performed in an isolated radiation enclosure not specifically designed for live-animal imaging. This requires equipment adapted to physiological monitoring and test-substance delivery, as well as shuttering to reduce the radiation dose. Experiment designs must also take into account the fixed location, size and orientation of the X-ray beam. This article describes the techniques developed to overcome the challenges involved in respiratory X-ray imaging of live animals at synchrotrons, now enabling increasingly sophisticated imaging protocols.

Failure Evaluation of a SiC/SiC Ceramic Matrix Composite During In-Situ Loading Using Micro X-ray Computed Tomography.

In this study, we have examined ceramic matrix composites with silicon carbide fibers in a melt-infiltrated silicon carbide matrix (SiC/SiC). We subjected samples to tensile loads while collecting micro X-ray computed tomography images. The results showed the expected crack slowing mechanisms and lower resistance to crack propagation where the fibers ran parallel and perpendicular to the applied load respectively. Cracking was shown to initiate not only from the surface but also from silicon inclusions. Post heat-treated samples showed longer fiber pull-out than the pristine samples, which was incompatible with previously proposed mechanisms. Evidence for oxidation was identified and new mechanisms based on oxidation or an oxidation assisted boron nitride phase transformation was therefore proposed to explain the long pull-out. The role of oxidation emphasizes the necessity of applying oxidation resistant coatings on SiC/SiC.

Development of a simple numerical model for trabecular bone structures.

PURPOSE: Advances in additive manufacturing processes are enabling the fabrication of surrogate bone structures for applications including use in high-resolution anthropomorphic phantoms. In this research, a simple numerical model is proposed that enables the generation of microarchitecture with similar statistical distribution to trabecular bone. METHODS: A human humerus, radius, ulna, and several vertebrae were scanned on the Imaging and Medical beamline at the Australian Synchrotron and the proposed numerical model was developed through the definition of two complex functions that encode the trabecular thickness and position-dependant spacing to generate volumetric surrogate trabecular structures. The structures reproduced those observed at 19 separate axial locations through the experimental bone volumes. The applicability of the model when incorporating a two-material approximation to absorption- and phase-contrast CT was also investigated through simulation. RESULTS: The synthetic structures, when compared with the real trabecular microarchitecture, yielded an average mean thickness error of 2 µm, and a mean difference in standard deviation of 33 µm for the humerus, 24 µm for the ulna and radius, and 15 µm for the vertebrae. Simulated absorption- and propagation-based phase contrast CT projection data were generated and reconstructed using the derived mathematical simplifications from the two-material approximation, and the phase-contrast effects were successfully demonstrated. CONCLUSIONS: The presented model reproduced trabecular distributions that could be used to generate phantoms for quality assurance and validation processes. The implication of utilizing a two-material approximation results in simplification of the additive manufacturing process and the generation of synthetic data that could be used for training of machine learning applications.

Live-pig-airway surface imaging and whole-pig CT at the Australian Synchrotron Imaging and Medical Beamline.

The Australian Synchrotron Imaging and Medical Beamline (IMBL) was designed to be the world's widest synchrotron X-ray beam, partly to enable clinical imaging and therapeutic applications for humans, as well as for imaging large-animal models. Our group is currently interested in imaging the airways of newly developed cystic fibrosis (CF) animal models that display human-like lung disease, such as the CF pig. One key outcome measure for assessing the effectiveness of CF airway therapies is the ability of the lung to clear inhaled particulates by mucociliary transit (MCT). This study extends the ex vivo sheep and pig tracheal-tissue studies previously performed by the authors at the IMBL. In the present study, attempts were made to determine whether the design of the IMBL is suitable for imaging tracheal MCT in live pigs. The movement of 200 µm-diameter high-refractive-index (HRI) glass-bead marker particles deposited onto the tracheal airway surface of eight live piglets was tracked and quantified and the MCT response to aerosol delivery was examined. A high-resolution computed tomographic (CT) whole-animal post-mortem scan of one pig was also performed to verify the large sample CT capabilities of the IMBL. MCT tracking particles were visible in all animals, and the automated MCT tracking algorithms used were able to identify and track many particles, but accuracy was reduced when particles moved faster than ∼6 mm min-1 (50 pixels between exposures), or when the particles touched or overlapped. Renderings were successfully made from the CT data set. Technical issues prevented use of reliable shuttering and hence radiation doses were variable. Since dose must be carefully controlled in future studies, estimates of the minimum achievable radiation doses using this experiment design are shown. In summary, this study demonstrated the suitability of the IMBL for large-animal tracheal MCT imaging, and for whole-animal CT.

Toward Improving Breast Cancer Imaging: Radiological Assessment of Propagation-Based Phase-Contrast CT Technology.

RATIONALE AND OBJECTIVES: This study employs clinical/radiological evaluation in establishing the optimum imaging conditions for breast cancer imaging using the X-ray propagation-based phase-contrast tomography. MATERIALS AND METHODS: Two series of experiments were conducted and in total 161 synchrotron-based computed tomography (CT) reconstructions of one breast mastectomy specimen were produced at different imaging conditions. Imaging factors include sample-to-detector distance, X-ray energy, CT reconstruction method, phase retrieval algorithm applied to the CT projection images and maximum intensity projection. Observers including breast radiologists and medical imaging experts compared the quality of the reconstructed images with reference images approximating the conventional (absorption) CT. Various radiological image quality attributes in a visual grading analysis design were used for the radiological assessments. RESULTS: The results show that the application of the longest achievable sample-to-detector distance (9.31 m), the lowest employed X-ray energy (32 keV), the full phase retrieval, and the maximum intensity projection can significantly improve the radiological quality of the image. Several combinations of imaging variables resulted in images with very high-quality scores. CONCLUSION: The results of the present study will support future experimental and clinical attempts to further optimize this innovative approach to breast cancer imaging.

Advantages of breast cancer visualization and characterization using synchrotron radiation phase-contrast tomography.

The aim of this study was to highlight the advantages that propagation-based phase-contrast computed tomography (PB-CT) with synchrotron radiation can provide in breast cancer diagnostics. For the first time, a fresh and intact mastectomy sample from a 60 year old patient was scanned on the IMBL beamline at the Australian Synchrotron in PB-CT mode and reconstructed. The clinical picture was described and characterized by an experienced breast radiologist, who underlined the advantages of providing diagnosis on a PB-CT volume rather than conventional two-dimensional modalities. Subsequently, the image quality was assessed by 11 breast radiologists and medical imaging experts using a radiological scoring system. The results indicate that, with the radiation dose delivered to the sample being equal, the accuracy of a diagnosis made on PB-CT images is significantly higher than one using conventional techniques.

Capturing the spatial variability of HIV epidemics in South Africa and Tanzania using routine healthcare facility data.

BACKGROUND: Large geographical variations in the intensity of the HIV epidemic in sub-Saharan Africa call for geographically targeted resource allocation where burdens are greatest. However, data available for mapping the geographic variability of HIV prevalence and detecting HIV 'hotspots' is scarce, and population-based surveillance data are not always available. Here, we evaluated the viability of using clinic-based HIV prevalence data to measure the spatial variability of HIV in South Africa and Tanzania. METHODS: Population-based and clinic-based HIV data from a small HIV hyper-endemic rural community in South Africa as well as for the country of Tanzania were used to map smoothed HIV prevalence using kernel interpolation techniques. Spatial variables were included in clinic-based models using co-kriging methods to assess whether cofactors improve clinic-based spatial HIV prevalence predictions. Clinic- and population-based smoothed prevalence maps were compared using partial rank correlation coefficients and residual local indicators of spatial autocorrelation. RESULTS: Routinely-collected clinic-based data captured most of the geographical heterogeneity described by population-based data but failed to detect some pockets of high prevalence. Analyses indicated that clinic-based data could accurately predict the spatial location of so-called HIV 'hotspots' in > 50% of the high HIV burden areas. CONCLUSION: Clinic-based data can be used to accurately map the broad spatial structure of HIV prevalence and to identify most of the areas where the burden of the infection is concentrated (HIV 'hotspots'). Where population-based data are not available, HIV data collected from health facilities may provide a second-best option to generate valid spatial prevalence estimates for geographical targeting and resource allocation.

Synchrotron radiation external beam rotational radiotherapy of breast cancer: proof of principle.

The principle of rotational summation of the absorbed dose for breast cancer treatment with orthovoltage X-ray beams was proposed by J. Boone in 2012. Here, use of X-ray synchrotron radiation for image guided external beam rotational radiotherapy treatment of breast cancer is proposed. Tumor irradiation occurs with the patient in the prone position hosted on a rotating bed, with her breast hanging from a hole in the bed, which rotates around a vertical axis passing through the tumor site. Horizontal collimation of the X-ray beam provides for whole breast or partial breast irradiation, while vertical translation of the bed and successive rotations allow for irradiation of the full tumor volume, with dose rates which permit also hypofractionated treatments. In this work, which follows a previous preliminary report, results are shown of a full series of measurements on polyethylene and acrylic cylindrical phantoms carried out at the Australian Synchrotron, confirmed by Geant4 Monte Carlo simulations, intended to demonstrate the proof of principle of the technique. Dose measurements were carried out with calibrated ion chambers, radiochromic films and thermoluminescence dosimeters. The photon energy investigated was 60 keV. Image guidance may occur with the transmitted beam for contrast-enhanced breast computed tomography. For a horizontal beam collimation of 1.5 cm and rotation around the central axis of a 14 cm-diameter polyethylene phantom, a periphery-to-center dose ratio of 14% was measured. The simulations showed that under the same conditions the dose ratio decreases with increasing photon energy down to 10% at 175 keV. These values are comparable with those achievable with conventional megavoltage radiotherapy of breast cancer with a medical linear accelerator. Dose painting was demonstrated with two off-center `cancer foci' with 1.3 Gy and 0.6 Gy target doses. The use of a radiosensitizing agent for dose enhancement is foreseen.

Bereavement support standards and bereavement care pathway for quality palliative care.

ABSTRACTObjective:Provision of bereavement support is an essential component of palliative care service delivery. While bereavement support is integral to palliative care, it is typically insufficiently resourced, under-researched, and not systematically applied. Our aim was to develop bereavement standards to assist palliative care services to provide targeted support to family caregivers. METHOD: We employed a multiple-methods design for our study, which included: (1) a literature review, (2) a survey of palliative care service providers in Australia, (3) interviews with national (Australian) and international experts, (4) key stakeholder workshops, and (5) a modified Delphi-type survey. RESULTS: A total of 10 standards were developed along with a pragmatic care pathway to assist palliative care services with implementation of the standards. SIGNIFICANCE OF RESULTS: The bereavement standards and care pathway constitute a key initiative in the evolution of bereavement support provided by palliative care services. Future endeavors should refine and examine the impact of these standards. Additional research is required to enhance systematic approaches to quality bereavement care.

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.

Preclinical radiotherapy at the Australian Synchrotron's Imaging and Medical Beamline: instrumentation, dosimetry and a small-animal feasibility study.

Therapeutic applications of synchrotron X-rays such as microbeam (MRT) and minibeam (MBRT) radiation therapy promise significant advantages over conventional clinical techniques for some diseases if successfully transferred to clinical practice. Preclinical studies show clear evidence that a number of normal tissues in animal models display a tolerance to much higher doses from MRT compared with conventional radiotherapy. However, a wide spread in the parameters studied makes it difficult to make any conclusions about the associated tumour control or normal tissue complication probabilities. To facilitate more systematic and reproducible preclinical synchrotron radiotherapy studies, a dedicated preclinical station including small-animal irradiation stage was designed and installed at the Imaging and Medical Beamline (IMBL) at the Australian Synchrotron. The stage was characterized in terms of the accuracy and reliability of the vertical scanning speed, as this is the key variable in dose delivery. The measured speed was found to be within 1% of the nominal speed for the range of speeds measured by an interferometer. Furthermore, dose measurements confirm the expected relationship between speed and dose and show that the measured dose is independent of the scan direction. Important dosimetric parameters such as peak dose, valley dose, the collimator output factor and peak-to-valley dose ratio are presented for 5 mm × 5 mm, 10 mm × 10 mm and 20 mm × 20 mm field sizes. Finally, a feasibility study on three glioma-bearing rats was performed. MRT and MBRT doses were prescribed to achieve an average dose of 65 Gy in the target, and magnetic resonance imaging follow-up was performed at various time points after irradiation to follow the tumour volume. Although it is impossible to draw conclusions on the different treatments with such a small number of animals, the feasibility of end-to-end preclinical synchrotron radiotherapy studies using the IMBL preclinical stage is demonstrated.