Correlative Nanoscale 3D Imaging of Structure and Composition in Extended Objects

Structure and composition at the nanoscale determine the behavior of biological systems and engineered materials. The drive to understand and control this behavior has placed strong demands on developing methods for high resolution imaging. In general, the improvement of three-dimensional (3D) resolution is accomplished by tightening constraints: reduced manageable specimen sizes, decreasing analyzable volumes, degrading contrasts, and increasing sample preparation efforts. Aiming to overcome these limitations, we present a non-destructive and multiple-contrast imaging technique, using principles of X-ray laminography, thus generalizing tomography towards laterally extended objects. We retain advantages that are usually restricted to 2D microscopic imaging, such as scanning of large areas and subsequent zooming-in towards a region of interest at the highest possible resolution. Our technique permits correlating the 3D structure and the elemental distribution yielding a high sensitivity to variations of the electron density via coherent imaging and to local trace element quantification through X-ray fluorescence. We demonstrate the method by imaging a lithographic nanostructure and an aluminum alloy. Analyzing a biological system, we visualize in lung tissue the subcellular response to toxic stress after exposure to nanotubes. We show that most of the nanotubes are trapped inside alveolar macrophages, while a small portion of the nanotubes has crossed the barrier to the cellular space of the alveolar wall. In general, our method is non-destructive and can be combined with different sample environmental or loading conditions. We therefore anticipate that correlative X-ray nano-laminography will enable a variety of in situ and in operando 3D studies

Thoughts about the optimum data acquisition geometry and time resolution of monochromatic beam x-ray diffraction microscopy experiments

International audienceSo far, 3D X-ray diffraction microscopy (3DXRD) and X-ray diffraction contrast tomography (DCT) experiments have typically been performed in forward scattering geometry, the detector intercepting diffraction cones up to limited opening angles below 30°. The extension of the current synchrotron–based methodology towards 3D orientation mapping of deformed microstructures with down to (sub-)micrometer spatial resolution will require a reduction of the pixel and hence sample size by one order of magnitude. This in turn relaxes the need for high energy beams and opens interesting possibilities for new acquisition geometries, taking advantage of improved spatial resolution and strain sensitivity at high diffraction angles. First results obtained in this acquisition geometry will be discussed and a comparison to polychromatic micro-diffraction experiments is drawn

[La microstructure 3D des matériaux polycristallins vue sous la lumière synchrotron]

International audienceSynchrotron radiation X-ray imaging and diffraction techniques offer new possibilities for non-destructive bulk characterization of polycrystalline materials. Minute changes in electron density (different crystallographic phases, cracks, porosities) can be detected using 3D imaging modes exploiting Fresnel diffraction and the coherence properties of third generation synchrotron beams. X-ray diffraction contrast tomography, a technique based on Bragg diffraction imaging, provides access to the 3D shape, orientation and elastic strain state of the individual grains from polycrystalline sample volumes containing several hundred up to a few thousand grains. Combining both imaging modalities allows a comprehensive description of the microstructure of the material at the micrometer length scale. Repeated observations during (interrupted) mechanical tests provide unprecedented insight into crystallographic and grain microstructure related aspects of polycrystal deformation and degradation mechanisms in materials, fulfilling some conditions on grain size and deformation state.Les techniques d'imagerie et de diffraction au rayonnement synchrotron offrent de nouvelles possibilités pour la caractérisation tridimensionnelle et non destructive des matériaux polycristallins. De faibles variations de densité électronique (phases secondaires, fissures, porosités) peuvent êtres détectées grâce à des modes d'imagerie qui exploitent la diffraction de Fresnel ainsi que la cohérence des faisceaux issus des sources synchrotron de troisième génération. La tomographie par contraste de diffraction, autre technique d'imagerie 3D basée sur la diffraction de Bragg, donne accès à la forme, l'orientation et l'état de déformation élastique des grains dans des volumes polycristallins contenant jusqu'à mille grains. La combinaison de ces deux modes d'imagerie permet de caractériser des matériaux polycristallins à l'échelle du micron. Des observations répétées lors d'essais mécaniques (interrompus) permettent d'analyser le rôle de la cristallographie locale sur les mécanismes de déformation et de dégradation dans des matériaux polycristallins, respectant certaines conditions sur la taille de grains, et/ou leur état de déformation

Valaciclovir to prevent Cytomegalovirus mediated adverse modulation of the immune system in ANCA-associated vasculitis (CANVAS):study protocol for a randomised controlled trial

BACKGROUND: The ANCA-associated vasculitides (AAV) are systemic autoimmune inflammatory disorders characterised by necrotising inflammation affecting small to medium-sized blood vessels. Despite improvements in survival, infection and cardiovascular disease remain leading causes of morbidity and mortality. Considerable evidence suggests that CD4 + CD28null T-cell expansions, predominantly seen in Cytomegalovirus (CMV) seropositive individuals, are associated with systemic dysregulation of immune function leading to a heightened risk of infection and cardiovascular disease. In patients with AAV, CD4 + CD28null expansions are driven by CMV and are associated with an increased risk of infection and mortality. The aim of this study is to explore in detail the ways in which CMV modulates the immune system and to determine whether treatment with valaciclovir blocks subclinical CMV reactivation in CMV seropositive AAV patients and ameliorates the CMV-induced adverse effects on the immune system. METHODS/DESIGN: CANVAS is a single-centre prospective open-label randomised controlled proof-of-concept trial of 50 adult CMV seropositive patients with stable AAV. Participants will be randomly allocated to receive valaciclovir orally (2 g QDS or reduced according to renal function) or no additional treatment for 6 months with an additional 6-month follow-up period. The primary outcome is the proportion of patients with CMV reactivation, as assessed by measurable viral load on quantitative blood and urine CMV polymerase chain reaction. The secondary outcomes are safety, change in the proportion of CD4+ CMV-specific T-cell population (defined as CD4 + CD28null cells) and change in soluble markers of inflammation from baseline to 6 months. Further tertiary and exploratory outcomes include persistence of the effect of valaciclovir on the proportion of CD4 + CD28null cells at 6 months post completion of treatment, change in the immune phenotype of CD4+ T cells and change in blood pressure and arterial stiffness parameters from baseline to 6 months. DISCUSSION: The results of this study will enable larger studies to be conducted to determine whether by controlling subclinical CMV reactivation, we can improve clinical endpoints such as infection and cardiovascular disease. The potential impact of this study is not limited to AAV, as CD4 + CD28null cells have been linked to adverse outcomes in other inflammatory conditions and in the context of an ageing immune system. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01633476 (registered 29 June 2012). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-016-1482-2) contains supplementary material, which is available to authorized users

Caractérisation 3D de la microstructure d'absorption et cristalline dans les matériaux polycristallins par tomographie en contraste de diffraction

International audienceno abstrac

[La microstructure 3D des matériaux polycristallins vue sous la lumière synchrotron]

International audienceSynchrotron radiation X-ray imaging and diffraction techniques offer new possibilities for non-destructive bulk characterization of polycrystalline materials. Minute changes in electron density (different crystallographic phases, cracks, porosities) can be detected using 3D imaging modes exploiting Fresnel diffraction and the coherence properties of third generation synchrotron beams. X-ray diffraction contrast tomography, a technique based on Bragg diffraction imaging, provides access to the 3D shape, orientation and elastic strain state of the individual grains from polycrystalline sample volumes containing several hundred up to a few thousand grains. Combining both imaging modalities allows a comprehensive description of the microstructure of the material at the micrometer length scale. Repeated observations during (interrupted) mechanical tests provide unprecedented insight into crystallographic and grain microstructure related aspects of polycrystal deformation and degradation mechanisms in materials, fulfilling some conditions on grain size and deformation state.Les techniques d'imagerie et de diffraction au rayonnement synchrotron offrent de nouvelles possibilités pour la caractérisation tridimensionnelle et non destructive des matériaux polycristallins. De faibles variations de densité électronique (phases secondaires, fissures, porosités) peuvent êtres détectées grâce à des modes d'imagerie qui exploitent la diffraction de Fresnel ainsi que la cohérence des faisceaux issus des sources synchrotron de troisième génération. La tomographie par contraste de diffraction, autre technique d'imagerie 3D basée sur la diffraction de Bragg, donne accès à la forme, l'orientation et l'état de déformation élastique des grains dans des volumes polycristallins contenant jusqu'à mille grains. La combinaison de ces deux modes d'imagerie permet de caractériser des matériaux polycristallins à l'échelle du micron. Des observations répétées lors d'essais mécaniques (interrompus) permettent d'analyser le rôle de la cristallographie locale sur les mécanismes de déformation et de dégradation dans des matériaux polycristallins, respectant certaines conditions sur la taille de grains, et/ou leur état de déformation

THOUGHTS ABOUT THE OPTIMUM DATA ACQUISITION GEOMETRYAND TIME RESOLUTION OF MONOCHROMATIC BEAM X‐RAY DIFFRACTION MICROSCOPY EXPERIMENTS

International audienceno abstrac

3-D growth of a short fatigue crack within a polycrystalline microstructure studied using combined diffraction and phase-contrast X-ray tomography

X-ray diffraction contrast tomography is a recently developed, non-destructive synchrotron imaging technique which characterizes microstructure and grain orientation in polycrystalline materials in three dimensions. By combining it with propagation-based phase-contrast tomography it is possible to get a full picture description for the analysis of local crack growth rate of short fatigue cracks in three dimensions: the three-dimensional crack morphology at different propagation stages, and the shape and orientation of the grains around the crack. An approach has been developed on the metastable beta titanium alloy Ti 21S that allows for visualization and analysis of the growth rate and crystallographic orientation of the fracture surface. © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved