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During the past decade microbeam radiation therapy has evolved from preclinical studies to a stage in which clinical trials can be planned, using spatially fractionated, highly collimated and high intensity beams like those generated at the x-ray ID17 beamline of the European Synchrotron Radiation Facility. The production of such microbeams typically between 25 and 100 μm full width at half maximum (FWHM) values and 100–400 μm center-to-center (c-t-c) spacings requires a multislit collimator either with fixed or adjustable microbeam width. The mechanical regularity of such devices is the most important property required to produce an array of identical microbeams. That ensures treatment reproducibility and reliable use of Monte Carlo-based treatment planning systems. New high precision wire cutting techniques allow the fabrication of these collimators made of tungsten carbide. We present a variable slit width collimator as well as a single slit device with a fixed setting of 50 μm FWHM and 400 μm c-t-c, both able to cover irradiation fields of 50 mm width, deemed to meet clinical requirements. Important improvements have reduced the standard deviation of 5.5 μm to less than 1 μm for a nominal FWHM value of 25 μm. The specifications of both devices, the methods used to measure these characteristics, and the results are presented. [ABSTRACT FROM AUTHOR]

Abstract: Microbeam Radiation Therapy (MRT) has the potential to treat infantile brain tumors when other kinds of radiotherapy would be excessively toxic to the developing normal brain. MRT uses extraordinarily high doses of X-rays but provides unusual resistance to radioneurotoxicity, presumably from the rapid migration of regenerative endothelial cells from dose “valleys” into dose “peaks”, i.e., into directly irradiated micro-slices of tissues. We will present a novel irradiation geometry which results in a tolerable valley dose for the normal tissue and a decreased peak-to-valley dose ratio (PVDR) in the tumor area by applying an innovative cross-firing technique. We propose an MRT technique to orthogonally crossfire two arrays of parallel, nonintersecting, mutually interspersed microbeams that produces tumoricidal doses with small PVDRs where the arrays meet and tolerable radiation doses to normal tissues between the microbeams proximal and distal to the tumor in the paths of the arrays. [Copyright &y& Elsevier]

Purpose: To present and validate a computer-based simulation platform dedicated for phase contrast xray breast imaging research. Methods: The software platform, developed at the Technical University of Varna on the basis of a previously validated x-ray imaging software simulator, comprises modules for object creation and for xray image formation. These modules were updated to take into account the refractive index for phase contrast imaging as well as implementation of the Fresnel-Kirchhoff diffraction theory of the propagating x-ray waves. Projection images are generated in an in-line acquisition geometry. To test and validate the platform, several phantoms differing in their complexity were constructed and imaged at 25 keV and 60 keV at the beamline ID17 of the European Synchrotron Radiation Facility. The software platform was used to design computational phantoms that mimic those used in the experimental study and to generate x-ray images in absorption and phase contrast modes. Results: The visual and quantitative results of the validation process showed an overall good correlation between simulated and experimental images and show the potential of this platform for research in phase contrast x-ray imaging of the breast. The application of the platform is demonstrated in a feasibility study for phase contrast images of complex inhomogeneous and anthropomorphic breast phantoms, compared to x-ray images generated in absorption mode. Conclusions: The improved visibility of mammographic structures suggests further investigation and optimisation of phase contrast x-ray breast imaging, especially when abnormalities are present. The software platform can be exploited also for educational purposes. [ABSTRACT FROM AUTHOR]

Abstract: Intensive synchrotron X-ray microbeams form an integral part of microbeam radiation therapy (MRT). MRT is a novel radiation medicine modality being developed for inoperable and otherwise untreatable brain tumours. The extremely high dose rate (∼20 kGy/s), laterally fractionated radiation field and steep dose gradients utilized in this therapy make real-time dosimetry a significant challenge. In order for this treatment to advance to the clinical trial stage of development real-time dosimetry systems must be developed. This paper demonstrates the capabilities of a new dosimetry system based on an epitaxial silicon detector. The system combines high spatial resolution and real-time readout and we have measured the lateral dose profile of the MRT radiation field which incorporates 59 X-ray microbeams. All microbeam peaks and valley regions between two microbeams are clearly resolved. The measured detector response at any point is reproducible to within 0.5% after scaling for the known synchrotron storage ring beam current lifetime. The variation of the lateral dose profile at different depths in a PMMA phantom has been measured with the results compared to those from Penelope Monte Carlo simulations. The trend in the measured response with depth agrees with the simulation data (within the experimental variation of the central five microbeams peaks and valleys measured). However the measured peak-to-valley ratio response is a factor of 4.5 ± 0.1 times lower than that expected. The disagreement was further investigated and shown to be contributed to by charge recombination effects at the low bias voltages used. [Copyright &y& Elsevier]

Synchrotron radiation is an innovative tool for the treatment of brain tumors. In the stereotactic synchrotron radiation therapy (SSRT) technique a radiation dose enhancement specific to the tumor is obtained. The tumor is loaded with a high atomic number (Z) element and it is irradiated in stereotactic conditions from several entrance angles. The aim of this work was to assess dosimetric properties of the SSRT for preparing clinical trials at the European Synchrotron Radiation Facility (ESRF). To estimate the possible risks, the doses received by the tumor and healthy tissues in the future clinical conditions have been calculated by using Monte Carlo simulations (PENELOPE code). The dose enhancement factors have been determined for different iodine concentrations in the tumor, several tumor positions, tumor sizes, and different beam sizes. A scheme for the dose escalation in the various phases of the clinical trials has been proposed. The biological equivalent doses and the normalized total doses received by the skull have been calculated in order to assure that the tolerance values are not reached. [ABSTRACT FROM AUTHOR]

Abstract: The radiotherapy clinical trials projects, both aiming at treating aggressive brain tumors, require several major modifications and new constructions at the ESRF ID17 Biomedical beamline. The application of the Stereotactic Synchrotron Radiation Therapy (SSRT) technique mainly necessitates an upgrade of the existing patient positioning system, which was formerly used for the angiography program. It will allow for accurate positioning, translation and rotation of the patient during the treatment. For the Microbeam Radiation Therapy (MRT) clinical trials project, a new white beam hutch will be constructed to accommodate a dedicated patient positioning system. Consequently, the existing control hutches and the related installations will also be completely refurbished. Furthermore, the foreseen installation of a second X-ray source, which will allow doubling the currently available photon flux at high energies, requires a redesign of most optical components to handle the increased power and power densities. Starting from the current ID17 Biomedical beamline layout, the paper will present an update of the different modification/construction projects, including the general organization and planning. [Copyright &y& Elsevier]

Reference Earth global models used by geophysicists are mostly constrained by analysing seismic waves that travel in the Earth. The interpretation of these seismological models in terms of chemical composition and temperature thus relies on the knowledge of the chemical composition, structure and elastic properties of some candidate materials relevant to geophysics. We will describe some recent advances in experimental mineral physics which yield essential information on the elastic properties of pertinent materials of Earth’s mantle and core. In particular, we show that inelastic X-ray scattering (IXS) proves to be a well suited spectroscopic technique for the study of phonon dispersion in materials under high pressure. Inelastic scattering experiments carried out on polycrystalline samples provide measurements of orientationally averaged longitudinal acoustic velocities whereas investigations on single crystals yield elastic moduli. Such a technique is thus highly interesting for mineral physicists and offers a great potential in providing essential elastic data and their pressure and/or temperature dependence on most compounds of geophysical interest. [Copyright &y& Elsevier]

Inelastic X-ray scattering (IXS) with meV energy resolution has become a valuable spectroscopic tool in the last 10 years, complementing the well-established coherent inelastic neutron scattering (INS) techniques. In the study of crystalline systems, IXS is the tool of choice in cases where either samples are available only in small quantities or where samples are studied under very high pressure. At the European Synchrotron Radiation Facility (ESRF), there are currently two beam-lines (ID16 and ID28) dedicated to phonon spectroscopy. In order to illustrate the present state of the art, we present two experiments that have been recently performed on the two beam-lines. [Copyright &y& Elsevier]

We present an experimental and theoretical investigation of the phonon dispersion relations in zinc blende (3C) SiC. The experimental data were obtained for the entire Brillouin zone by inelastic x-ray scattering (IXS) using a synchrotron radiation source. Eigenvector analysis is performed with the aid of state-of-the-art linear response first principles calculations based on density functional theory. The theoretical predictions reproduce the experimental phonon dispersion remarkably well. These results are compared with data obtained previously for the (111) direction by Raman spectroscopy using several SiC polytypes and the backfolding technique. IXS data for 4H modification along the c axis are also reported. [ABSTRACT FROM AUTHOR]

Background: Resistance to radiotherapy is frequently encountered in patients with glioblastoma multiforme. It is caused at least partially by the high glutathione content in the tumour tissue. Therefore, the administration of the glutathione synthesis inhibitor Buthionine-SR-Sulfoximine (BSO) should increase survival time.Methods: BSO was tested in combination with an experimental synchrotron-based treatment, microbeam radiation therapy (MRT), characterized by spatially and periodically alternating microscopic dose distribution. One hundred thousand F98 glioma cells were injected into the right cerebral hemisphere of adult male Fischer rats to generate an orthotopic small animal model of a highly malignant brain tumour in a very advanced stage. Therapy was scheduled for day 13 after tumour cell implantation. At this time, 12.5% of the animals had already died from their disease. The surviving 24 tumour-bearing animals were randomly distributed in three experimental groups: subjected to MRT alone (Group A), to MRT plus BSO (Group B) and tumour-bearing untreated controls (Group C). Thus, half of the irradiated animals received an injection of 100 μM BSO into the tumour two hours before radiotherapy. Additional tumour-free animals, mirroring the treatment of the tumour-bearing animals, were included in the experiment. MRT was administered in bi-directional mode with arrays of quasi-parallel beams crossing at the tumour location. The width of the microbeams was ≈28 μm with a center-to-center distance of ≈400 μm, a peak dose of 350 Gy, and a valley dose of 9 Gy in the normal tissue and 18 Gy at the tumour location; thus, the peak to valley dose ratio (PVDR) was 31.Results: After tumour-cell implantation, otherwise untreated rats had a mean survival time of 15 days. Twenty days after implantation, 62.5% of the animals receiving MRT alone (group A) and 75% of the rats given MRT + BSO (group B) were still alive. Thirty days after implantation, survival was 12.5% in Group A and 62.5% in Group B. There were no survivors on or beyond day 35 in Group A, but 25% were still alive in Group B. Thus, rats which underwent MRT with adjuvant BSO injection experienced the largest survival gain.Conclusions: In this pilot project using an orthotopic small animal model of advanced malignant brain tumour, the injection of the glutathione inhibitor BSO with MRT significantly increased mean survival time. [ABSTRACT FROM AUTHOR]