Platelets after burn injury - hemostasis and beyond.

Burn injuries are common and often life-threatening trauma. With this trauma comes an interruption of normal hemostasis, with distinct impacts on platelets. Our interest in the relationships between burn injury and platelet function stems from two key perspectives: platelet function is a vital component of acute responses to injury, and furthermore the incidence of cardiovascular disease (CVD) is higher in burn survivors compared to the general population. This review explores the impact of burn injury on coagulation, platelet function, and the participation of platelets in immunopathology. Potential avenues of further research are explored, and consideration is given to what therapies may be appropriate for mediating post-burn thrombopathology.

A Monte Carlo model of synchrotron radiotherapy shows good agreement with experimental dosimetry measurements: Data from the imaging and medical beamline at the Australian Synchrotron.

Experimental measurement of Synchrotron Radiotherapy (SyncRT) doses is challenging, especially for Microbeam Radiotherapy (MRT), which is characterised by very high dynamic ranges with spatial resolutions on the micrometer scale. Monte Carlo (MC) simulation is considered a gold standard for accurate dose calculation in radiotherapy, and is therefore routinely relied upon to produce verification data. We present a MC model for Australian Synchrotron's Imaging and Medical Beamline (IMBL), which is capable of generating accurate dosimetry data to inform and/or verify SyncRT experiments. Our MC model showed excellent agreement with dosimetric measurement for Synchrotron Broadbeam Radiotherapy (SBBR). Our MC model is also the first to achieve validation for MRT, using two methods of dosimetry, to within clinical tolerances of 5% for a 20×20 mm2 field size, except for surface measurements at 5 mm depth, which remained to within good agreement of 7.5%. Our experimental methodology has allowed us to control measurement uncertainties for MRT doses to within 5-6%, which has also not been previously achieved, and provides a confidence which until now has been lacking in MRT validation studies. The MC model is suitable for SyncRT dose calculation of clinically relevant field sizes at the IMBL, and can be extended to include medical beamlines at other Synchrotron facilities as well. The presented MC model will be used as a validation tool for treatment planning dose calculation algorithms, and is an important step towards veterinary SyncRT trials at the Australian Synchrotron.

Coherency image analysis to quantify collagen architecture: implications in scar assessment.

An important histological difference between normal, uninjured dermis and scar tissue such as that found in keloid scars is the pattern (morphological architecture) in which the collagen is deposited and arranged. In the uninjured dermis, collagen bundle architecture appears randomly organized (or in a basket weave formation), whereas in pathological conditions such as keloid scar tissue, collagen bundles are often found in whorls or in a hypotrophic scar collagen is more densely packed in a parallel configuration. In the case of skin, a scar disables the dermis, leaving it weaker, stiff and with a loss of optimal functionality. The absence of objective and quantifiable assessments of collagen orientation is a major bottleneck in monitoring progression of scar therapeutics. In this article, a novel quantitative approach for analyzing collagen orientation is reported. The methodology is demonstrated using collagen produced by cells in a model scar environment and examines collagen remodeling post-TGFß stimulation in vitro. The method is shown to be reliable and effective in identifying significant coherency differences in the collagen deposited by human keloid scar cells. The technique is also compared for analysing collagen architecture in rat sections of normal, scarred skin and tendon tissue. Results demonstrate that the proposed computational method provides a fast and robust way of analyzing collagen orientation in a manner surpassing existing methods. This study establishes this methodology as a preliminary means of monitoring in vitro and in tissue treatment modalities which are expected to alter collagen morphology.

Absorbed dose determination in kilovoltage X-ray synchrotron radiation using alanine dosimeters.

Alanine dosimeters from the National Physical Laboratory (NPL) in the UK were irradiated using kilovoltage synchrotron radiation at the imaging and medical beam line (IMBL) at the Australian Synchrotron. A 20 × 20 mm2 area was irradiated by scanning the phantom containing the alanine through the 1 mm × 20 mm beam at a constant velocity. The polychromatic beam had an average energy of 95 keV and nominal absorbed dose to water rate of 250 Gy/s. The absorbed dose to water in the solid water phantom was first determined using a PTW Model 31014 PinPoint ionization chamber traceable to a graphite calorimeter. The alanine was read out at NPL using correction factors determined for 60Co, traceable to NPL standards, and a published energy correction was applied to correct for the effect of the synchrotron beam quality. The ratio of the doses determined by alanine at NPL and those determined at the synchrotron was 0.975 (standard uncertainty 0.042) when alanine energy correction factors published by Waldeland et al. (Waldeland E, Hole E O, Sagstuen E and Malinen E, Med. Phys. 2010, 37, 3569) were used, and 0.996 (standard uncertainty 0.031) when factors by Anton et al. (Anton M, Büermann L., Phys Med Biol. 2015 60 6113-29) were used. The results provide additional verification of the IMBL dosimetry.

Absolute dosimetry on a dynamically scanned sample for synchrotron radiotherapy using graphite calorimetry and ionization chambers.

The absolute dose delivered to a dynamically scanned sample in the Imaging and Medical Beamline (IMBL) on the Australian Synchrotron was measured with a graphite calorimeter anticipated to be established as a primary standard for synchrotron dosimetry. The calorimetry was compared to measurements using a free-air chamber (FAC), a PTW 31 014 Pinpoint ionization chamber, and a PTW 34 001 Roos ionization chamber. The IMBL beam height is limited to approximately 2 mm. To produce clinically useful beams of a few centimetres the beam must be scanned in the vertical direction. In practice it is the patient/detector that is scanned and the scanning velocity defines the dose that is delivered. The calorimeter, FAC, and Roos chamber measure the dose area product which is then converted to central axis dose with the scanned beam area derived from Monte Carlo (MC) simulations and film measurements. The Pinpoint chamber measures the central axis dose directly and does not require beam area measurements. The calorimeter and FAC measure dose from first principles. The calorimetry requires conversion of the measured absorbed dose to graphite to absorbed dose to water using MC calculations with the EGSnrc code. Air kerma measurements from the free air chamber were converted to absorbed dose to water using the AAPM TG-61 protocol. The two ionization chambers are secondary standards requiring calibration with kilovoltage x-ray tubes. The Roos and Pinpoint chambers were calibrated against the Australian primary standard for air kerma at the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA). Agreement of order 2% or better was obtained between the calorimetry and ionization chambers. The FAC measured a dose 3-5% higher than the calorimetry, within the stated uncertainties.

High spatial resolution dosimetric response maps for radiotherapy ionization chambers measured using kilovoltage synchrotron radiation.

Small circular beams of synchrotron radiation (0.1 mm and 0.4 mm in diameter) were used to irradiate ionization chambers of the types commonly used in radiotherapy. By scanning the chamber through the beam and measuring the ionization current, a spatial map of the dosimetric response of the chamber was recorded. The technique is able to distinguish contributions to the large-field ionization current from the chamber walls, central electrode and chamber stem. Scans were recorded for the NE 2571 Farmer chamber, the PTW 30013, IBA FC65-G Farmer-type chambers, the NE 2611A and IBA CC13 thimble chambers, the PTW 31006 and 31014 pinpoint chambers, the PTW Roos and Advanced Markus plane-parallel chambers, and the PTW 23342 thin-window soft x-ray chamber. In all cases, large contributions to the response arise from areas where the incident beam grazes the cavity surfaces. Quantitative as well as qualitative information about the relative chamber response was extracted from the maps, including the relative contribution of the central electrode. Line scans using monochromatic beams show the effect of the photon energy on the chamber response. For Farmer-type chambers, a simple Monte Carlo model was in good agreement with the measured response.

Absolute x-ray dosimetry on a synchrotron medical beam line with a graphite calorimeter.

PURPOSE: The absolute dose rate of the Imaging and Medical Beamline (IMBL) on the Australian Synchrotron was measured with a graphite calorimeter. The calorimetry results were compared to measurements from the existing free-air chamber, to provide a robust determination of the absolute dose in the synchrotron beam and provide confidence in the first implementation of a graphite calorimeter on a synchrotron medical beam line. METHODS: The graphite calorimeter has a core which rises in temperature when irradiated by the beam. A collimated x-ray beam from the synchrotron with well-defined edges was used to partially irradiate the core. Two filtration sets were used, one corresponding to an average beam energy of about 80 keV, with dose rate about 50 Gy/s, and the second filtration set corresponding to average beam energy of 90 keV, with dose rate about 20 Gy/s. The temperature rise from this beam was measured by a calibrated thermistor embedded in the core which was then converted to absorbed dose to graphite by multiplying the rise in temperature by the specific heat capacity for graphite and the ratio of cross-sectional areas of the core and beam. Conversion of the measured absorbed dose to graphite to absorbed dose to water was achieved using Monte Carlo calculations with the EGSnrc code. The air kerma measurements from the free-air chamber were converted to absorbed dose to water using the AAPM TG-61 protocol. RESULTS: Absolute measurements of the IMBL dose rate were made using the graphite calorimeter and compared to measurements with the free-air chamber. The measurements were at three different depths in graphite and two different filtrations. The calorimetry measurements at depths in graphite show agreement within 1% with free-air chamber measurements, when converted to absorbed dose to water. The calorimetry at the surface and free-air chamber results show agreement of order 3% when converted to absorbed dose to water. The combined standard uncertainty is 3.9%. CONCLUSIONS: The good agreement of the graphite calorimeter and free-air chamber results indicates that both devices are performing as expected. Further investigations at higher dose rates than 50 Gy/s are planned. At higher dose rates, recombination effects for the free-air chamber are much higher and expected to lead to much larger uncertainties. Since the graphite calorimeter does not have problems associated with dose rate, it is an appropriate primary standard detector for the synchrotron IMBL x rays and is the more accurate dosimeter for the higher dose rates expected in radiotherapy applications.

On the evolution and relative merits of hard X-ray phase-contrast imaging methods.

This review provides a brief overview, albeit from a somewhat personal perspective, of the evolution and key features of various hard X-ray phase-contrast imaging (PCI) methods of current interest in connection with translation to a wide range of imaging applications. Although such methods have already found wide-ranging applications using synchrotron sources, application to dynamic studies in a laboratory/clinical context, for example for in vivo imaging, has been slow due to the current limitations in the brilliance of compact laboratory sources and the availability of suitable high-performance X-ray detectors. On the theoretical side, promising new PCI methods are evolving which can record both components of the phase gradient in a single exposure and which can accept a relatively large spectral bandpass. In order to help to identify the most promising paths forward, we make some suggestions as to how the various PCI methods might be compared for performance with a particular view to identifying those which are the most efficient, given the fact that source performance is currently a key limiting factor on the improved performance and applicability of PCI systems, especially in the context of dynamic sample studies. The rapid ongoing development of both suitable improved sources and detectors gives strong encouragement to the view that hard X-ray PCI methods are poised for improved performance and an even wider range of applications in the near future.

A quantitative study of monochromatic X-ray transmission through zinc wires.

X-ray transmission through zinc wires of various diameters has been investigated systematically at different beam energies and sample-to-detector distances at the Shanghai Synchrotron Radiation Facility. This analysis shows that the experimentally measured transmission differs significantly from the theoretical estimation unless an appropriate point-spread function/line-spread function (PSF/LSF) is incorporated in the analysis. A number of other possible factors which may contribute to the observed inconsistencies were also assessed and these factors included higher harmonics and fluorescence; however, it was determined that these were not the dominant contributors underlying the inconsistencies. The investigation has demonstrated that the PSF/LSF is a major factor for consideration in quantitative X-ray micro-computed tomography.

Weight-bearing-induced displacement and migration over time of fracture fragments following split depression fractures of the lateral tibial plateau: a case series with radiostereometric analysis.

We investigated the stability of seven Schatzker type II fractures of the lateral tibial plateau treated by subchondral screws and a buttress plate followed by immediate partial weight-bearing. In order to assess the stability of the fracture, weight-bearing inducible displacements of the fracture fragments and their migration over a one-year period were measured by differentially loaded radiostereometric analysis and standard radiostereometric analysis, respectively. The mean inducible craniocaudal fracture fragment displacements measured -0.30 mm (-0.73 to 0.02) at two weeks and 0.00 mm (-0.12 to 0.15) at 52 weeks. All inducible displacements were elastic in nature under all loads at each examination during follow-up. At one year, the mean craniocaudal migration of the fracture fragments was -0.34 mm (-1.64 to 1.51). Using radiostereometric methods, this case series has shown that in the Schatzker type II fractures investigated, internal fixation with subchondral screws and a buttress plate provided adequate stability to allow immediate post-operative partial weight-bearing, without harmful consequences.

A laboratory based system for laue micro x-ray diffraction.

A laboratory diffraction system capable of illuminating individual grains in a polycrystalline matrix is described. Using a microfocus x-ray source equipped with a tungsten anode and prefigured monocapillary optic, a micro-x-ray diffraction system with a 10 microm beam was developed. The beam profile generated by the ellipsoidal capillary was determined using the "knife edge" approach. Measurement of the capillary performance, indicated a beam divergence of 14 mrad and a useable energy bandpass from 5.5 to 19 keV. Utilizing the polychromatic nature of the incident x-ray beam and application of the Laue indexing software package X-Ray Micro-Diffraction Analysis Software, the orientation and deviatoric strain of single grains in a polycrystalline material can be studied. To highlight the system potential the grain orientation and strain distribution of individual grains in a polycrystalline magnesium alloy (Mg 0.2 wt % Nd) was mapped before and after tensile loading. A basal (0002) orientation was identified in the as-rolled annealed alloy; after tensile loading some grains were observed to undergo an orientation change of 30 degrees with respect to (0002). The applied uniaxial load was measured as an increase in the deviatoric tensile strain parallel to the load axis.

Generalized eikonal of partially coherent beams and its use in quantitative imaging.

The generalized eikonal of a partially coherent paraxial wave is introduced via a differential equation describing the evolution of the time-averaged intensity. The theoretical formalism provides an analytical tool for the study of partially coherent imaging systems. It also makes possible quantitative phase retrieval and compositional mapping of weakly absorbing samples using phase-contrast imaging with broadband polychromatic radiation of known spectral distribution. An experimental demonstration is presented of the quantitative reconstruction of the projected thickness of a sample, given a phase-contrast image obtained using a polychromatic microfocus x-ray source.

X-ray omni microscopy.

The science of wave-field phase retrieval and phase measurement is sufficiently mature to permit the routine reconstruction, over a given plane, of the complex wave-function associated with certain coherent forward-propagating scalar wave-fields. This reconstruction gives total knowledge of the information that has been encoded in the complex wave-field by passage through a sample of interest. Such total knowledge is powerful, because it permits the emulation in software of the subsequent action of an infinite variety of coherent imaging systems. Such 'virtual optics', in which software forms a natural extension of the 'hardware optics' in an imaging system, may be useful in contexts such as quantitative atom and X-ray imaging, in which optical elements such as beam-splitters and lenses can be realized in software rather than optical hardware. Here, we develop the requisite theory to describe such hybrid virtual-physical imaging systems, which we term 'omni optics' because of their infinite flexibility. We then give an experimental demonstration of these ideas by showing that a lensless X-ray point projection microscope can, when equipped with the appropriate software, emulate an infinite variety of optical imaging systems including those which yield interferograms, Zernike phase contrast, Schlieren imaging and diffraction-enhanced imaging.

Quantitative X-ray projection microscopy: phase-contrast and multi-spectral imaging.

We outline a new approach to X-ray projection microscopy in a scanning electron microscope (SEM), which exploits phase contrast to boost the quality and information content of images. These developments have been made possible by the combination of a high-brightness field-emission gun (FEG)-based SEM, direct detection CCD technology and new phase retrieval algorithms. Using this approach we have been able to obtain spatial resolution of < 0.2 micro m and have demonstrated novel features such as: (i) phase-contrast enhanced visibility of high spatial frequency image features (e.g. edges and boundaries) over a wide energy range; (ii) energy-resolved imaging to simultaneously produce multiple quasi-monochromatic images using broad-band polychromatic illumination; (iii) easy implementation of microtomography; (iv) rapid and robust phase/amplitude-retrieval algorithms to enable new real-time and quantitative modes of microscopic imaging. These algorithms can also be applied successfully to recover object-plane information from intermediate-field images, unlocking the potentially greater contrast and resolution of the intermediate-field regime. Widespread applications are envisaged for fields such as materials science, biological and biomedical research and microelectronics device inspection. Some illustrative examples are presented. The quantitative methods described here are also very relevant to projection microscopy using other sources of radiation, such as visible light and electrons.

Quantitative analysis of two-component samples using in-line hard X-ray images.

Methods for rapid quantitative phase-sensitive X-ray imaging of non-crystalline samples consisting of two distinct components are investigated. The transverse spatial distribution of the projected thickness of each component is reconstructed by computer processing of in-line images collected using synchrotron-generated hard X-rays and a position-sensitive detector with submicrometre spatial resolution. Different imaging techniques and associated image-processing algorithms are considered, with relative advantages and difficulties of each approach compared. A possible generalization of the method for the case of n-component samples is briefly discussed.

Wavelength extrapolation to zero extinction: a gamma-ray case. The quantitative effect of the extrapolation function on the kinematical limit value.

To ensure that a true zero-extinction kinematical limit value has been attained by extrapolation of a series of measurements on one reflection, the proper dependence of a function of F versus the function of the physical variable involved in the measurements has to be identified. To demonstrate this point, the multiwavelength gamma-ray data on seven reflections of NiF(2) reported by Palmer & Jauch [Acta Cryst. (1995), A51, 662--667] have been utilized. A new physical component has been introduced into the relationship between diffracted intensity and wavelength--that due to the decrease in angular divergence of diffraction from crystallites with decrease in wavelength. For gamma-rays, this leads to a function of F(2) in respect of wavelength, viz F(2) = F(0)(2) - alphalambda + betalambda(2), which is different from that derived from Zachariasen-type models, viz F(2) = F(0)(2) - klambda(2). Comparison of the limit values according to Palmer & Jauch and according to Mathieson & Stevenson demonstrates the advantage of the functional dependence proposed in this study.

The role of radiographic phase-contrast imaging in the development of intracochlear electrode arrays.

OBJECTIVE: This study describes the application of a new radiographic imaging modality, phase-contrast radiography, to in vitro human temporal bone imaging and investigates its use in the development of new electrode arrays for cochlear implants. BACKGROUND: The development of perimodiolar electrode arrays for cochlear implants requires detailed information from postoperative radiologic assessment on the position of the array in relation to the cochlear structures. Current standard radiographic techniques provide only limited details. MATERIALS AND METHODS: Nucleus standard electrode arrays and perimodiolar Contour electrode arrays were implanted into the scala tympani of 11 human temporal bones. Both conventional and phase-contrast radiographs were taken of each temporal bone for comparative purposes. RESULTS: Phase-contrast imaging provides better visualization of anatomic details of the inner ear and of the structure of the intracochlear electrode array, and better definition of electrode location in relation to cochlear walls. CONCLUSION: Phase-contrast radiography offers significant improvement over conventional radiography in images of in vitro human temporal bones. It seems to be a valuable tool in the development of intracochlear electrode arrays and cochlear implant research. However, this new radiographic technique still requires certain computational and physics challenges to be addressed before its clinical use can be established.

Quantitative in-line phase-contrast imaging with multienergy X rays.

We present a new method for quantitative nondestructive characterization of objects by x-ray phase-contrast imaging. Spatial distributions of the projected values of the complex refractive index in the sample are reconstructed by processing near-field images collected at a fixed sample-to-detector distance using a polychromatic incident beam and an energy-sensitive area detector, such as a CCD used in the photon-counting spectroscopy mode. The method has the potential advantages of decreased radiation dose and increased accuracy compared to conventional techniques of x-ray imaging.

Quantitative methods in phase-contrast x-ray imaging.

A new method for extracting quantitative information from phase-contrast x-ray images obtained with microfocus x-ray sources is presented. The proposed technique allows rapid noninvasive characterization of the internal structure of thick optically opaque organic samples. The method does not generally involve any sample preparation and does not need any x-ray optical elements (such as monochromators, zone plates, or interferometers). As a consequence, samples can be imaged in vivo or in vitro, and the images are free from optical aberrations. While alternative techniques of x-ray phase-contrast imaging usually require expensive synchrotron radiation sources, our method can be implemented with conventional, albeit microfocus, x-ray tubes, which greatly enhances its practicality. In the present work, we develop the theoretical framework, perform numerical simulations, and present the first experimental results, demonstrating the viability of the proposed approach. We believe that this method should find wide-ranging applications in clinical radiology and medical research.