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ISTerre is part of Labex OSUG@2020. Use of the Geochem- istry–Mineralogy platform at ISTerre is acknowledged. The authors wish to aknowledge the ESRF for provision of beam time (MA4498). We are also thankful to Dr Pierre-Olivier Autran for useful insights on tomographic reconstructions and Dr Marta Majkut for discussions on grain orientation calcu- lations. The authors also thank Dr Irina Snigireva and Dr Nathaniel Findling for SEM characterization of the samples and Dr Catherine Dejoie for complementary high-resolution powder diffraction data from the ID22 beamline of the ESRF., The mechanism of hydration of calcium sulfate hemihydrate (CaSO4 0.5H2O) to form gypsum (CaSO4 2H2O) was studied by combining scanning 3D X-ray diffraction (s3DXRD) and phase contrast tomography (PCT) to determine in situ the spatial and crystallographic relationship between these two phases. From s3DXRD measurements, the crystallographic structure, orientation and position of the crystalline grains in the sample during the hydration reaction were obtained, while the PCT reconstructions allowed visualization of the 3D shapes of the crystals during the reaction. This multi-scale study unfolds structural and morphological evidence of the dissolution–precipitation process of the gypsum plaster system, providing insights into the reactivity of specific crystallographic facets of the hemihydrate. In this work, epitaxial growth of gypsum crystals on the hemihydrate grains was not observed.

Ex vivo X-ray phase contrast tomography of amyotrophic lateral sclerosis of a SOD1G93A mouse model is presented. Quantification of neuronal and vascular alteration in the central nervous system is described., Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting motor neurons. Pre-clinical studies drive the development of animal models that well mimic ALS disorder and enable both the dissection of disease processes and an early assessment of therapy efficacy. A comprehensive knowledge of neuronal and vascular lesions in the brain and spinal cord is an essential factor to understand the development of the disease. Spatial resolution and bidimensional imaging are important drawbacks limiting current neuroimaging tools, while neuropathology relies on protocols that may alter tissue chemistry and structure. In contrast, recent ex vivo studies in mice demonstrated that X-ray phase-contrast tomography enables study of the 3D distribution of both vasculature and neuronal networks, without sample sectioning or use of staining. Here we present our findings on ex vivo SOD1G93A ALS mice spinal cord at a micrometric scale. An unprecedented direct quantification of neuro-vascular alterations at different stages of the disease is shown.

While numerous transgenic mouse strains have been produced to model the formation of amyloid-β (Aβ) plaques in the brain, efficient methods for whole-brain 3D analysis of Aβ deposits are lacking. Moreover, standard immunohistochemistry performed on brain slices precludes any shape analysis of Aβ plaques. The present study shows how in-line (propagation-based) X-ray phase-contrast tomography (XPCT) combined with ethanol-induced brain sample dehydration enables hippocampus-wide detection and morphometric analysis of Aβ plaques. Performed in three distinct Alzheimer mouse strains, the proposed workflow identified differences in signal intensity and 3D shape parameters: 3xTg displayed a different type of Aβ plaques, with a larger volume and area, greater elongation, flatness and mean breadth, and more intense average signal than J20 and APP/PS1. As a label-free non-destructive technique, XPCT can be combined with standard immunohistochemistry. XPCT virtual histology could thus become instrumental in quantifying the 3D spreading and the morphological impact of seeding when studying prion-like properties of Aβ aggregates in animal models of Alzheimer’s disease. This is Part II of a series of two articles reporting the value of in-line XPCT for virtual histology of the brain; Part I shows how in-line XPCT enables 3D myelin mapping in the whole rodent brain and in human autopsy brain tissue.HighlightsX-ray phase-contrast tomography (XPCT) enables whole brain detection of Aβ plaquesMorphometric parameters of Aβ plaques may be readily retrieved from XPCT dataNew shape parameters were successfully extracted from three Alzheimer’s disease modelsA Fiji-based “biologist-friendly” analysis workflow is proposed and sharedXPCT is a powerful virtual histology tool that requires minimal sample preparationGraphical abstract

Technological advancements in X-ray imaging using bright and coherent synchrotron sources now allows to decouple sample size and resolution, while maintaining high sensitivity to the microstructure of soft, partially dehydrated tissues. The recently developed imaging technique, hierarchical phase-contrast tomography, is a comprehensive approach to address the challenge of organ-scale (up to tens of centimeters) soft tissue imaging with resolution and sensitivity down to the cellular level. Using this technique, we imaged ex vivo an entire human left lung at an isotropic voxel size of 25.08 μm along with local zooms down to 6.05 - 6.5 μm and 2.45 - 2.5 μm in voxel size. The high tissue contrast offered by the fourth-generation synchrotron source at the European Synchrotron Radiation Facility reveals complex multiscale anatomical constitution of the human lung from the macroscopic (centimeter) down to the microscopic (micrometer) scale. The dataset provides complete organ-scale 3D information of the secondary pulmonary lobules and delineates the microstructure of lung nodules with unprecedented detail.

Imaging intact human organs from the organ to the cellular scale in three dimensions is a goal of biomedical imaging. To meet this challenge, we developed hierarchical phase-contrast tomography (HiP-CT), an X-ray phase propagation technique using the European Synchrotron Radiation Facility (ESRF)’s Extremely Brilliant Source (EBS). The spatial coherence of the ESRF-EBS combined with our beamline equipment, sample preparation and scanning developments enabled us to perform non-destructive, three-dimensional (3D) scans with hierarchically increasing resolution at any location in whole human organs. We applied HiP-CT to image five intact human organ types: brain, lung, heart, kidney and spleen. HiP-CT provided a structural overview of each whole organ followed by multiple higher-resolution volumes of interest, capturing organotypic functional units and certain individual specialized cells within intact human organs. We demonstrate the potential applications of HiP-CT through quantification and morphometry of glomeruli in an intact human kidney and identification of regional changes in the tissue architecture in a lung from a deceased donor with coronavirus disease 2019 (COVID-19).

International audience

The detection of CTCs in a blood sample is a challenging task due to their rarity and variety. We develop a new label-free and all-optical approach at the lab-on-chip scale for the detection of CTCs based on morphological biomarkers. In particular, we design a microfluidic device to be combined with a phase-contrast tomography system to carry out quantitative measurements of the three-dimensional structure of each single cell in a blood sample. In such device, two aspects are conjugated: on the one hand, the cells need to perform at least one complete rotation within the field of view of the imaging apparatus; on the other hand, the highest possible throughput has to be achieved, yet without deforming the cells significantly, which would impede their tomographic reconstruction. In this contribution, the finite-element-simulation-based preliminary design of a microfluidic device that would allow the achievement of the aforementioned objectives for cells with different shape and deformability is presented.

NeuroImage 199, 70 - 80 (2019). doi:10.1016/j.neuroimage.2019.05.043, Knowledge of the three-dimensional (3d) neuronal cytoarchitecture is an important factor in order to understand the connection between tissue structure and function or to visualize pathological changes in neurodegenerative diseases or tumor development. The gold standard in neuropathology is histology, a technique which provides insights into the cellular organization based on sectioning of the sample. Conventional histology, however, misses the complete 3d information as only individual two-dimensional slices through the object are available. In this work, we use propagation-based phase-contrast x-ray tomography to perform 3d virtual histology on cerebellar tissue from mice. This technique enables us to non-invasively visualize the entire 3d density distribution of the examined samples at isotropic (sub-)cellular resolution. One central challenge, however, of the technique is the fact that contrast for important structural features can be easily lost due to small electron density differences, notably between the cells and surrounding tissue. Here, we evaluate the influence of different embedding media, which are intermediate steps in sample preparation for classical histology, on contrast formation and examine the applicability of the different sample preparations both at a synchrotron-based holotomography setup as well as a laboratory source., Published by Academic Press, Orlando, Fla.

Laboratory and synchrotron X-ray tomography are powerful tools for non-invasive studies of biological samples at micrometric resolution. In particular, the development of phase contrast imaging is enabling the visualization of sample details with a small range of attenuation coefficients, thus allowing in-depth analyses of anatomical and histological structures. Reproductive medicine is starting to profit from these techniques, mainly applied to animal models. This study reports the first imaging of human ovarian tissue where the samples consisted of surgically obtained millimetre fragments, properly fixed, stained with osmium tetroxide and included in epoxydic resin. Samples were imaged by the use of propagation phase contrast synchrotron radiation micro-computed tomography (microCT), obtained at the SYRMEP beamline of Elettra light source (Trieste, Italy), and X-ray absorption microCT at the Theoretical Biology MicroCT Imaging Laboratory in Vienna, Austria. The reconstructed microCT images were compared with the soft X-ray absorption and phase contrast images acquired at the TwinMic beamline of Elettra in order to help with the identification of structures. The resulting images allow the regions of the cortex and medulla of the ovary to be distinguished, identifying early-stage follicles and visualizing the distribution of blood vessels. The study opens to further application of micro-resolved 3D imaging to improve the understanding of human ovary's structure and support diagnostics as well as advances in reproductive technologies.

Cardiovascular diseases (CVDs) affect the myocardium and vasculature, inducing remodelling of the heart from cellular to whole organ level. To assess their impact at micro and macroscopic level, multi-resolution imaging techniques that provide high quality images without sample alteration and in 3D are necessary: requirements not fulfilled by most of current methods. In this paper, we take advantage of the non-destructive time-efficient 3D multiscale capabilities of synchrotron Propagation-based X-Ray Phase Contrast Imaging (PB-X-PCI) to study a wide range of cardiac tissue characteristics in one healthy and three different diseased rat models. With a dedicated image processing pipeline, PB-X-PCI images are analysed in order to show its capability to assess different cardiac tissue components at both macroscopic and microscopic levels. The presented technique evaluates in detail the overall cardiac morphology, myocyte aggregate orientation, vasculature changes, fibrosis formation and nearly single cell arrangement. Our results agree with conventional histology and literature. This study demonstrates that synchrotron PB-X-PCI, combined with image processing tools, is a powerful technique for multi-resolution structural investigation of the heart ex-vivo. Therefore, the proposed approach can improve the understanding of the multiscale remodelling processes occurring in CVDs, and the comprehensive and fast assessment of future interventional approaches., Scientific Reports, 9, ISSN:2045-2322

International audience; Crack initiation and propagation under high-cycle fatigue conditions have been investigated for a polycrystalline Ni-based superalloy by in-situ synchrotron assisted diffraction and phase contrast tomography. The cracks nucleated along the longest coherent twin boundaries pre-existing on the specimen surface, that were well oriented for slip and that presented a large elastic incompatibility across them. Moreover, the propagation of microstructurally short cracks was found to be determined by the easy slip transfer paths across the pre-existing grain boundaries. This information can only be obtained by characterization techniques like the ones presented here that provide the full set of 3D microstructural information.

Human organs are complex, three-dimensional and multiscale systems. Spatially mapping the human body down through its hierarchy, from entire organs to their individual functional units and specialised cells, is a major obstacle to fully understanding health and disease. To meet this challenge, we developed hierarchical phase-contrast tomography (HiP-CT), an X-ray phase propagation technique utilising the European Synchrotron Radiation Facility’s Extremely Brilliant Source: the world’s first high-energy 4th generation X-ray source. HiP-CT enabled three-dimensional and non-destructive imaging at near-micron resolution in soft tissues at one hundred thousand times the voxel size whilst maintaining the organ’s structure. We applied HiP-CT to image five intact human parenchymal organs: brain, lung, heart, kidney and spleen. These were hierarchically assessed with HiP-CT, providing a structural overview of the whole organ alongside detail of the organ’s individual functional units and cells. The potential applications of HiP-CT were demonstrated through quantification and morphometry of glomeruli in an intact human kidney, and identification of regional changes to the architecture of the air-tissue interface and alveolar morphology in the lung of a deceased COVID-19 patient. Overall, we show that HiP-CT is a powerful tool which can provide a comprehensive picture of structural information for whole intact human organs, encompassing precise details on functional units and their constituent cells to better understand human health and disease.

A review is presented on the strategic use of scattering and imaging tools to design immunologic complexes based on porous silica for oral vaccine formulations., This article summarizes developments attained in oral vaccine formulations based on the encapsulation of antigen proteins inside porous silica matrices. These vaccine vehicles show great efficacy in protecting the proteins from the harsh acidic stomach medium, allowing the Peyer’s patches in the small intestine to be reached and consequently enhancing immunity. Focusing on the pioneering research conducted at the Butantan Institute in Brazil, the optimization of the antigen encapsulation yield is reported, as well as their distribution inside the meso- and macroporous network of the porous silica. As the development of vaccines requires proper inclusion of antigens in the antibody cells, X-ray crystallography is one of the most commonly used techniques to unveil the structure of antibody-combining sites with protein antigens. Thus structural characterization and modelling of pure antigen structures, showing different dimensions, as well as their complexes, such as silica with encapsulated hepatitis B virus-like particles and diphtheria anatoxin, were performed using small-angle X-ray scattering, X-ray absorption spectroscopy, X-ray phase contrast tomography, and neutron and X-ray imaging. By combining crystallography with dynamic light scattering and transmission electron microscopy, a clearer picture of the proposed vaccine complexes is shown. Additionally, the stability of the immunogenic complex at different pH values and temperatures was checked and the efficacy of the proposed oral immunogenic complex was demonstrated. The latter was obtained by comparing the antibodies in mice with variable high and low antibody responses.

This chapter introduces the latest X-ray CT scanners that are commercially available at the time that this book was written and the state-of-the-art synchrotron X-ray tomography, as well as superior examples of their application. In writing this chapter, many of the manufacturers of these X-ray CT scanners were directly approached for information regarding the characteristics of the products from each company and their notable application examples. Manufacturers have provided detailed specifications, which are normally not included even in catalogs, for this book. X-ray CT scanners are classified as general-use X-ray CT scanners for industrial use, high-energy industrial X-ray CT scanners, high-resolution industrial X-ray CT scanners, high-functionality industrial X-ray CT scanners, in-line inspection device and X-ray tomography using synchrotron radiation. The X-ray tomography using synchrotron radiation are also subdivided into projection-type X-ray tomography, imaging-type X-ray tomography, phase-contrast tomography, fast tomography, tomography of elemental concentrations, and tomography for polycrystalline structures. This chapter provides plenty of actual examples of 3D/4D images in a wide range of disciplines, including material development (e.g. polymers, ceramics, and batteries), natural resource exploration (e.g. oil and minerals), and bioengineering. This chapter also describes the selection of devices and conditions and realities of 3D imaging including sample size and X-ray energy selection.

Advanced engineering materials 23(11), 2001188 (2021). doi:10.1002/adem.202001188 special issue: "Neutrons and Synchrotron Radiation - Unique Tools for the Characterization of Materials", The 3D structural investigation of soft tissue samples under near physiological conditions is challenging as most established techniques require embedding, staining, or cutting samples. Such manipulations can induce artifacts or result in a tremendous workload by, e.g., the preparation of multiple 2D images to retrieve the volume information. A non-invasive technique allowing to image the soft tissue in a 3D fashion is propagation-based phase contrast computed tomography. We explore the methods' unique properties to assess the 3D distribution and size of human chondrocytes within collagen scaffolds in a liquid environment without embedding. To seek if the identification of differences in cell distribution is possible, we have seeded cartilage cells on collagen scaffolds that were unstimulated or stimulated by alternating electric fields for 7 days. Analysis of the 3D cell distributions reveals that the migration depth of the chondrocytes into the scaffold is nearly doubled along with the total number of cells due to the applied electric field. Further analysis shows no specific size distribution of the chondrogenic cells. Our results indicate that propagation-based phase contrast computed tomography is a suitable tool to determine the 3D distribution of cells within a biomaterial investigated under aqueous conditions., Published by Deutsche Gesellschaft fu��r Materialkunde, Frankfurt, M.

The ability of biomedical imaging data to be of quantitative nature is getting increasingly important with the ongoing developments in data science. In contrast to conventional attenuation-based X-ray imaging, grating-based phase contrast computed tomography (GBPC-CT) is a phase contrast micro-CT imaging technique that can provide high soft tissue contrast at high spatial resolution. While there is a variety of different phase contrast imaging techniques, GBPC-CT can be applied with laboratory X-ray sources and enables quantitative determination of electron density and effective atomic number. In this review article, we present quantitative GBPC-CT with the focus on biomedical applications.

Noise magnitude in conventional attenuation X-ray tomography (CT) is strongly dependent on the pixel size and/or the geometrical magnification, thereby limiting the possibility of achieving high-resolution low-dose CT imaging. In this context, the use of Propagation-Based Imaging (PBI) phase-contrast technique coupled with the application of a suitable Phase-Retrieval (PhR) filter is a valuable tool to overcome such limitation. In fact, at fixed radiation dose, the noise dependence on the effective pixel size when the PhR filter is applied is much shallower with respect to conventional CT imaging. Making use of a theoretical framework developed by other authors, this work demonstrates quantitatively the dependence of CT image noise on pixel size and magnification in PBI. Calculations are compared with experimental images of a breast specimen imaged at the SYRMEP beamline at the Elettra synchrotron facility (Trieste, Italy), with a CdTe photon-counting detector in PBI configuration. The results, expressed in terms of Signal-to-Noise Ratio (SNR) gain due to the PhR application, show a good agreement between predictions and experimental data at all pixel pitches and magnifications, quantitatively demonstrating the importance of going towards detectors featuring smaller pixels (or higher spatial resolution) to fully exploit the advantages of PBI and PhR. Specifically, SNR gain up to a factor of 20 is observed at the smallest pixel pitch (60 μ m) and largest magnification (1.40). At the same time, as predicted theoretically, larger magnifications correspond to lower image noise (or higher SNR) when PhR is applied: this trend is unparalleled in attenuation-based CT imaging where larger magnifications, hence smaller effective pixel sizes, lead to a higher noise.

X-ray phase contrast tomography (XPCT) is widely used for 3D imaging of objects with weak contrast in X-ray absorption index but strong contrast in refractive index decrement. To reconstruct an object imaged using XPCT, phase retrieval algorithms are first used to estimate the X-ray phase projections, which is the 2D projection of the refractive index decrement, at each view. Phase retrieval is followed by refractive index decrement reconstruction from the phase projections using an algorithm such as filtered back projection (FBP). In practice, phase retrieval is most commonly solved by approximating it as a linear inverse problem. However, this linear approximation often results in artifacts and blurring when the conditions for the approximation are violated. In this paper, we formulate phase retrieval as a non-linear inverse problem, where we solve for the transmission function, which is the negative exponential of the projections, from XPCT measurements. We use a constraint to enforce proportionality between phase and absorption projections. We do not use constraints such as large Fresnel number, slowly varying phase, or Born/Rytov approximations. Our approach also does not require any regularization parameter tuning since there is no explicit sparsity enforcing regularization function. We validate the performance of our non-linear phase retrieval (NLPR) method using both simulated and real synchrotron datasets. We compare NLPR with a popular linear phase retrieval (LPR) approach and show that NLPR achieves sharper reconstructions with higher quantitative accuracy., Comment: 2020 IS&T International Symposium on Electronic Imaging

Objectives: Light microscopical analysis in two dimensions, combined with immunohistochemistry, is presently the gold standard to describe the enteric nervous system (ENS). Our aim was to assess the usefulness of three-dimensional (3D) imaging by X-ray phase-contrast tomography in evaluating the ENS of the human bowel. Material and methods: Myenteric ganglia were identified in full-thickness biopsies of the ileum and colon by hematoxylin & eosin staining. A1-mm biopsy punch was taken from the paraffin blocks and placed into a Kapton® tube for subsequent tomographic investigation. The samples were scanned, without further preparation, using phase-contrast tomography at two different scales: overview scans (performed with laboratory setups), which allowed localization of the nervous tissue (∼1µm effective voxel size); and high-resolution scans (performed with a synchrotron endstation), which imaged localized regions of 320x320x320 µm3 (176 nm effective voxel size). Results: The contrast allowed us to follow the shape and the size changes of the ganglia, as well as to study their cellular components together with the cells and cellular projections of the periganglional space. Furthermore, it was possible to show the 3D network of the myenteric plexus and to quantify its volume within the samples. Conclusions: Phase-contrast X-ray tomography can be applied for volume analyses of the human ENS and to study tissue components in unstained paraffin-embedded tissue biopsies. This technique could potentially be used to study disease mechanisms, and to compare healthy and diseased tissues in clinical research.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

High-throughput single-cell analysis is a challenging target for implementing advanced biomedical applications. An excellent candidate for this aim is label-free tomographic phase microscopy (TPM). In this paper, some of the methods used to obtain TPM are reviewed, analyzing advantages and disadvantages of each of them. Moreover, an alternative tomographic technique is described for live cells analysis, and future trends of the method are foreseen. In particular, by exploiting random rolling of cells while they are flowing along a microfluidic channel, it is possible to obtain phase-contrast tomography thus obtaining complete retrieval of both 3D-position and orientation of rotating cells. Thus, a priori knowledge of such information is no longer needed. This approach extremely simplifies the optical system avoiding any mechanical/optical scanning of light source. The proof is given for different classes of biosamples, red-blood-cells (RBCs) and diatom algae. Accurate characterization of each type of cells is reported and compared to that obtained by other tomographic techniques.

Artifact removal algorithms are crucial for image quality in computed tomography. Many ring artifact removal algorithms have been proposed in conventional X-ray absorption computed tomography, but relatively fewer algorithms were suggested for differential X-ray phase contrast imaging. In this paper, a novel method is proposed to eliminate the ring artifacts caused by grating imperfections in X-ray phase contrast tomography. This method requires 360-degree projection data and exploits the anti-symmetry of conjugate rays to locate the artifact regions. Moreover, an interpolation scheme for sinogram-domain is proposed to correct artifacts. Experimental results show that the algorithm performs well in the case of severe artifacts.

Structural examination of human heart specimens at the microscopic level is a prerequisite for understanding congenital heart diseases. It is desirable not to destroy or alter the properties of such specimens because of their scarcity. However, many of the currently available imaging techniques either destroy the specimen through sectioning or alter the chemical and mechanical properties of the specimen through staining and contrast agent injection. As a result, subsequent studies may not be possible. X-ray phase-contrast tomography is an imaging modality for biological soft tissues that does not destroy or alter the properties of the specimen. The feasibility of X-ray phase-contrast tomography for the structural examination of heart specimens was tested using infantile and fetal heart specimens without congenital diseases. X-ray phase-contrast tomography was carried out at the SPring-8 synchrotron radiation facility using the Talbot grating interferometer at the bending magnet beamline BL20B2 to visualize the structure of five non-pretreated whole heart specimens obtained by autopsy. High-resolution, three-dimensional images were obtained for all specimens. The images clearly showed the myocardial structure, coronary vessels, and conduction bundle. X-ray phase-contrast tomography allows high-resolution, three-dimensional imaging of human heart specimens. Intact imaging using X-ray phase-contrast tomography can contribute to further structural investigation of heart specimens with congenital heart diseases. Electronic supplementary material The online version of this article (doi:10.1007/s00246-016-1527-z) contains supplementary material, which is available to authorized users.

Ancient remains from humans, animals and plants hold valuable information about our history. X-ray imaging methods are often, because of their non-destructive nature, used in the analysis of such s ...

Alzheimer's disease (AD), the most common form of dementia, is a progressive neurodegenerative disorder associated with aberrant production of beta-amyloid (Aβ) peptide depositing in brain as amyloid plaques. While animal models allow investigation of disease progression and therapeutic efficacy, technology to fully dissect the pathological mechanisms of this complex disease at cellular and vascular levels is lacking. X-ray phase contrast tomography (XPCT) is an advanced non-destructive 3D multi-scale direct imaging from the cell through to the whole brain, with exceptional spatial and contrast resolution. We exploit XPCT to simultaneously analyse disease-relevant vascular and neuronal networks in AD mouse brain, without sectioning and staining. The findings clearly show the different typologies and internal structures of Aβ plaques, together with their interaction with patho/physiological cellular and neuro-vascular microenvironment. XPCT enables for the first time a detailed visualization of amyloid-angiopathy at capillary level, which is impossible to achieve with other approaches. XPCT emerges as added-value technology to explore AD mouse brain as a whole, preserving tissue chemistry and structure, enabling the comparison of physiological vs. pathological states at the level of crucial disease targets. In-vivo translation will permit to monitor emerging therapeutic approaches and possibly shed new light on pathological mechanisms of neurodegenerative diseases.

Developments in X-Ray Tomography XII, San Diego, United States, 11 Aug 2019 - 15 Aug 2019; Proceedings (2019). doi:10.1117/12.2528432, In the present work, we evaluate and compare the contrast and resolution obtained on different neuronal tissues with propagation-based x-ray phase contrast computed tomography (PB-CT). At our laboratory-based liquid metal-jet setup, we obtain overview datasets at sub-micron resolution of mm3 -sized volumes. In order to evaluate these parameters down to the sub-cellular level, we utilize the synchrotron endstation GINIX at P10, DESY. At this dedicated endstation1 developed and operated by our group, we utilize x-ray waveguide optics for highresolution cone-beam scans at strong geometrical magnification M. Exploiting this multi-scale approach, we investigate the image quality of cerebellum tissue treated by different heavy-metal stains. In addition, we study the electron density contrast in unstained tissues. Different embedding media are utilized depending on the stain, which also significantly affects contrast and image quality. With this work, we want to contribute to an optimized sample preparation to study the neuronal architecture of the brain tissue in greater detail in three dimensions (3d)., Published by VDE-Verl., Berlin

Advanced X-ray phase-contrast tomography (XPCT) and modern computing technologies allow extremely fragile papyrus rolls to be efficiently analyzed from micro- to macro-levels. 3D virtual study of the Herculaneum papyri structure provides a unique opportunity not only for the tracking of the valuable texts contained in them, but also for reconstructing their original format and the historical events undergone by them, including modern ways to unroll them. In particular, XPCT combined with scanning electron microscopy and fluorescence analysis looks into the world of ancient bookrolls in a way that has never been imagined before. From this point of view, XPCT and computing technologies serve as unique tools for the nondestructive investigation, conservation, and exploitation of this extraordinary cultural heritage. This research shows that Herculaneum papyri disclose priceless information not only for scholars of papyrology, ancient philosophy and literature, but also for scientists from other fields.

Advanced engineering materials 23(11), 2001347 (2021). doi:10.1002/adem.202001347 special issue: "Neutrons and Synchrotron Radiation - Unique Tools for the Characterization of Materials", Cavitation under constrained tension is a critical failure phenomenon in rubber parts. For laboratory tests, strain constraints can be generated using disk-shaped rubber samples, that is, pancake specimens. Due to suppressed transverse contractibility, the dominating hydrostatic tensile stress, which is the highest in the center part of a pancake specimen, causes an internal failure process controlled by the formation and growth of cavities. Laboratory X-ray microtomography (��CT) is a powerful tool to monitor the evolution of a cavity population considering various aspects of geometrical as well as microstructural constraints. In the case of carbon black���reinforced styrene-butadiene rubber, microscopic cavities are surrounded by a region of significantly lower material density. Due to detection limits, this region cannot be analyzed in depth with ��CT. In this study, synchrotron X-ray microtomography (SR��CT) in combination with a modular load frame is used, for the first time, to investigate the damaging phenomenon of cavitation in rubbers. Due to the high phase contrast that can be achieved only by SR��CT, the microstructure of regions of lower material density can be analyzed and, as a result, tiny satellite cavities are identified in the walls of neighboring microscopic cavities., Published by Deutsche Gesellschaft fu��r Materialkunde, Frankfurt, M.

A new nonlinear level-set regularization method to reconstruct the complex refractive index distribution with in-line phase contrast tomography measurements is presented under the assumption that the index is piecewise constant. The nonlinear iterative approach is based on the Frechet derivative of the intensity recorded at a single propagation distance and for several projection angles. The algorithm is successfully applied to a multi-material object for several noise levels. Better reconstruction results are achieved with a stochastic perturbation of the level-set function. This evolution corresponds to a stochastic evolution of the shape of the reconstructed regions. The reconstruction errors can be further decreased with topological derivatives. The different algorithms are tested on various multi-material objects.

International audience; Theranostics is an innovative research field that aims to develop high target specificity cancer treatments by administering small metal-based nanoparticles (NPs). This new generation of compounds exhibits diagnostic and therapeutic properties due to the high atomic number of their metal component. In the framework of a combined research program on low dose X-ray imaging and theranostic NPs, X-ray Phase Contrast Tomography (XPCT) was performed at ESRF using a 3 μm pixel optical system on two samples: a mouse brain bearing melanoma metastases injected with gadolinium NPs and, a mouse liver injected with gold NPs. XPCT is a non-destructive technique suitable to achieve the 3D reconstruction of a specimen and, widely used at micro-scale to detect abnormalities of the vessels, which are associated to the tumor growth or to the development of neurodegenerative diseases. Moreover, XPCT represents a promising and complementary tool to study the biodistribution of theranostic NPs in biological materials, thanks to the strong contrast with respect to soft tissues that metal-based NPs provide in radiological images. This work is relied on an original imaging approach based on the evaluation of the contrast differences between the images acquired below and above K-edge energies, as a proof of the certain localization of NPs. We will present different methods aiming to enhance the localization of NPs and a 3D map of their distribution in large volume of tissues.

Tissue engineering, which is aimed at producing “lab-grown” organs and tissues, could revolutionise modern medicine by overcoming the shortage of donor organs. Imaging is key to virtually every aspect of this research; however, the gold standard methods (e.g. histology and electron microscopy) have significant shortcomings, preventing important investigations from being done. Most prominently, they rely upon a destructive sample preparation, making them incompatible with small animal imaging, which is however indispensable for preclinical studies. X-ray phase contrast computed tomography, which is sensitive to phase shifts induced by a sample, has the potential to solve this issue. This chapter provides an overview of laboratory implementations of x-ray phase contrast tomography (as opposed to synchrotron implementations, which are discussed elsewhere in this book) and their application to tissue engineering and related areas.

We report on the application of the multi-aperture analyser X-ray Phase-Contrast imaging (XPCI) technique to the three-dimensional imaging of breast tissue samples. The experiment was conducted at the SYRMEP beamline (Elettra synchrotron, Italy) with a monochromatic X-ray beam. Along with the presentation of the methodology and resulting images, the potential extension of this approach to enable in-vivo applications at acceptable doses is discussed.

Computed tomography is making a significant impact in the field of materials science in recent years. In this paper the authors report on advances made in three areas of characterization and also identified where further research needs to be focused. First we report on a new approach to data analysis called “Data Constrained Modelling (DCM)” in which compositional tomography can be undertaken rather than adsorption or phase contrast tomography. This is achieved by collecting X-ray CT data at different energies and then combining the datasets to reconstruct 3D compositional tomography. Second, on the application of this approach to inhibited primers typical of those used in the aerospace industry. Aerospace primers are effectively composite materials containing inorganic phases which are bound together with a polymer. Understanding the materials science of these systems requires information over several orders of magnitude in length-scale. In this paper we report on how DCM can be used to extend our understanding at the smaller length scales at the limits of resolution of the technique. The third and final advance is in extending the approach to include 4-dimensional studies. In this case we examine the primer before and after leaching. This process causes changes in the primer which can be both detected and quantified using the above approach.

Phase contrast tomography is a high sensitivity medical imaging technique. Several regularization methods have been used in the literature to obtain stable solutions for the phase retrieval or the phase contrast tomography problems. Yet, the functional framework and the convergence properties of the methods have not been studied in detail. In this work, the convergence properties of regularization approaches for phase retrieval and phase contrast tomography are investigated.

We present an approach towards four dimensional (4d) movies of materials, showing dynamic processes within the entire 3d structure. The method is based on tomographic reconstruction on dynamically curved paths using a motion model estimated by optical flow techniques, considerably reducing the typical motion artefacts of dynamic tomography. At the same time we exploit x-ray phase contrast based on free propagation to enhance the signal from micron scale structure recorded with illumination times down to a millisecond (ms). The concept is demonstrated by observing the burning process of a match stick in 4d, using high speed synchrotron phase contrast x-ray tomography recordings. The resulting movies reveal the structural changes of the wood cells during the combustion.