A versatile x-ray microtomography station for biomedical imaging and materials research.

We examine the projection approximation in the context of propagation-based phase contrast imaging using hard x-rays. Specifically, we consider the case of a cylinder or a rounded edge, as a simple model for the edges of many biological samples. The Argand-plane signature of a propagation-based phase contrast fringe from the edge of a cylinder is studied, and the evolution of this signature with propagation. This, along with experimental images obtained using a synchrotron source, reveals how propagation within the scattering volume is not fully described in the projection approximation's ray-based approach. This means that phase contrast fringes are underestimated by the projection approximation at a short object-to-detector propagation distance, namely a distance comparable to the free-space propagation within the volume. This failure of the projection approximation may become non-negligible in the detailed study of small anatomical features deep within a large body. Nevertheless, the projection approximation matches the exact solution for a larger propagation distance typical of those used in biomedical phase contrast imaging.

We present a comparison for high-resolution imaging with a laboratory source between grating-based (GBI) and propagation-based (PBI) x-ray phase-contrast imaging. The comparison is done through simulations and experiments using a liquid-metal-jet x-ray microfocus source. Radiation doses required for detection in projection images are simulated as a function of the diameter of a cylindrical sample. Using monochromatic radiation, simulations show a lower dose requirement for PBI for small object features and a lower dose for GBI for larger object features. Using polychromatic radiation, such as that from a laboratory microfocus source, experiments and simulations show a lower dose requirement for PBI for a large range of feature sizes. Tested on a biological sample, GBI shows higher noise levels than PBI, but its advantage of quantitative refractive index reconstruction for multi-material samples becomes apparent.

To investigate the properties of tomographic grating-based phase contrast imaging with respect to its noise power spectrum and the energy dependence of the achievable contrast to noise ratio. Tomographic simulations of an object with 11 cm diameter constituted of materials of biological interest were conducted at different energies ranging from 25 to 85 keV by using a wave propagation approach. Using a Monte Carlo simulation of the x-ray attenuation within the object, it is verified that the simulated measurement deposits the same dose within the object at each energy. The noise in reconstructed phase contrast computed tomography images shows a maximum at low spatial frequencies. The contrast to noise ratio reaches a maximum around 45 keV for the simulated object. The general dependence of the contrast to noise on the energy appears to be independent of the material. Compared with reconstructed absorption contrast images, the reconstructed phase contrast images show sometimes better, sometimes worse, and sometimes similar contrast to noise, depending on the material and the energy. Phase contrast images provide additional information to the conventional absorption contrast images and might thus be useful for medical applications. However, the observed noise power spectrum in reconstructed phase contrast images implies that the usual trade-off between noise and resolution is less efficient for phase contrast imaging compared with absorption contrast imaging. Therefore, high-resolution imaging is a strength of phase contrast imaging, but low-resolution imaging is not. This might hamper the clinical application of the method, in cases where a low spatial resolution is sufficient for diagnosis.

High-resolution scanning transmission electron microscopy

A method of tomographic phase retrieval is developed for multi-material objects whose components each has a distinct complex refractive index. The phase-retrieval algorithm, based on the Transport-of-Intensity equation, utilizes propagation-based X-ray phase contrast images acquired at a single defocus distance for each tomographic projection. The method requires a priori knowledge of the complex refractive index for each material present in the sample, together with the total projected thickness of the object at each orientation. The requirement of only a single defocus distance per projection simplifies the experimental setup and imposes no additional dose compared to conventional tomography. The algorithm was implemented using phase contrast data acquired at the SPring-8 Synchrotron facility in Japan. The three-dimensional (3D) complex refractive index distribution of a multi-material test object was quantitatively reconstructed using a single X-ray phase-contrast image per projection. The technique is robust in the presence of noise, compared to conventional absorption based tomography.

Summary form only given. Productive and cost effective use of semiconductor manufacturing equipment is a primary concern in semiconductor fabs today. As equipment costs continue to escalate, semiconductor manufacturers are focusing their efforts on Computer Integrated Manufacturing (CIM) to bolster productivity, improve yields, and reduce the cost of ownership. Equipment Integration can play a key role in these sophisticated CIM systems by bridging the gap between factory computer systems and process equipment. To implement efficient and effective equipment integration, the semiconductor manufacturer must overcome the following obstacles: high implementation costs; difficult technical implementation; long development cycles; finite resources; limited operational functionality. Specifically, the equipment's communication interface (CI) contributes to those obstacles through: Limited communication interface functionality; Unique equipment communication interfaces; Unpredictable equipment communication interfaces; Poor reuse of integration practices and software from factory to factory. Motorola is addressing these obstacles by implementing a program to improve equipment communication interface consistency, predictability, and functionality. To improve equipment communication predictability, Motorola utilizes improved CI characterization tools techniques that thoroughly exercise the equipment's CI. To improve interface consistency and functionality, Motorola is establishing partnerships with equipment vendors and characterization software suppliers. These partnerships provide the foundation for improved CI quality and adherence to SEMI standards before a product is shipped to Motorola. Mr. Guy Davis will share his perspective on how standards, procedures, and software tools can improve the quality and reduce the cost and cycletime involved in equipment integration. He will discuss the benefits realized when software suppliers, system integrators, equipment providers, and semiconductor manufacturers are working together.

High resolution synchrotron-based radiography and tomography using hard X-rays at the BAM line (BESSY II)

Portal vein imaging is an important method for investigating portal venous disorders. However, the diagnostic requirements are not usually satisfied when using single imaging techniques. Diagnostic accuracy can be improved by combining different imaging techniques. Contrast agents that can be used for combined imaging modalities are needed. In this study, the feasibility of using microbubbles containing gadolinium (MCG) as contrast agents for both phase contrast imaging (PCI) and magnetic resonance imaging (MRI) are investigated. MCG were made by encapsulating sulfur hexafluoride (SF6) gas with gadolinium and lyophilized powder. Absorption contrast imaging (ACI) and PCI of MCG were performed and compared in vitro. MCG were injected into the main portal trunk of living rats. PCI and MRI were performed at 2 min and 10 min after MCG injection, respectively. PCI exploited the differences in the refractive index and visibly showed the MCG, which were not detectable by ACI. PCI could facilitate clear revelation of the MCG-infused portal veins. The diameter of the portal veins could be determined by the largest MCG in the same portal vein. The minimum diameter of clearly detected portal veins was about 300 µm by MRI. These results indicate that MCG could enhance both PCI and MRI for imaging portal veins. The detection sensitivity of PCI and MRI could compensate for each other when using MCG contrast agents for animals.

The aim of this study was to assess the influence of micro-computed tomography (micro-CT) voxel size on the evaluation of debris accumulation after passive ultrasonic irrigation (PUI) in curved root canals prepared with rotary nickel-titanium files. Mesial root canals (n = 24) of mandibular molars with curvature between 25° and 35° were prepared using ProDesign Logic 30/.05 (PDL) or HyFlex EDM 25/.08 (HEDM). PUI was performed after root canal preparation of all root canals. The specimens were scanned using high-resolution (5 μm voxel size) micro-CT imaging before and after experimental procedures. The percentage of debris was analyzed in the middle and apical thirds using images with 5, 10 and 20 μm voxel sizes. Data were compared using unpaired and paired Student's t-test, ANOVA and Tukey's statistical tests (α = 0.05). There were no differences among the debris analyses performed at different voxel sizes (5, 10 and 20 μm) (p > 0.05). The percentage of debris was similar between the root canals prepared by PDL and HEDM before and after PUI (p > 0.05). In both groups, the percentage of debris decreased in the middle third after PUI (p < 0.05). Within the limitations of this ex vivo study, it can be concluded that the voxel sizes evaluated did not have a significant impact on the analysis of accumulated debris. However, the results showed a tendency for detection of more debris in the analysis performed using a lower voxel size. PUI decreased the debris accumulation in the middle third of curved root canals.

In available synchrotron radiation facilities all over the world, the size of electron beam bunch has distinct difference between the horizontal direction and the vertical direction at the cross section vertical to electron moving direction. It will cause low symmetry of source size in horizontal and vertical directions, and result in big difference in the spacial resolution and phase contrast between these two directions in synchrotron radiation X-ray in-line phase contrast imaging. The superior resolution and phase contrast of one direction will couple with the inferior ones of the other direction in actual object imaging, this interaction will degrade both spacial resolution and phase contrast of the whole image and lead to poor image quality. In this paper, a four-knife white beam slit is used in Beijing synchrotron radiation facility (BSRF) 4W1A beamline to adjust source size in horizontal and vertical directions and restrict the point spread function (PSF) of source, the source size is limited from 1.23 mm (horizontal)×0.46 mm (vertical) to 0.35 mm×0.35 mm. By this way, a highly symmetric effective X-ray source is obtained. The symmetry of source size is improved from 2.7 to about 1. Although the total X-ray flux loses 99.95%, the X-ray flux density is only reduced to 22%. It because total flux is taken account of the expanded spot size due to divergence, while flux density is mainly related to effective source size, which is limited not severely as expanded spot size by white beam slit. The flux density reduction by this method is not a critical defect in high resolution X-ray phase contrast imaging and can be improved by other ways. The polyamide fiber net is imaged using X-ray in-line phase contrast imaging at 4W1A, BSRF. Diameter of fiber is about 50 microns, X-ray energy is 13 keV, the effective pixel size is 0.325 micron, the experiment images are obtained at object-to-detector distances of 4, 10, 16, 36, 100, 200 and 300 mm with source-to-object distance of about 43 m. The results show that when source size in horizontal direction is limited from 1.23 to 0.35 mm (symmetry of source size is about 1 at this condition), the maximal phase contrast of image is advanced from 0.057 to 0.35. It means the density sensitivity is promoted about 5 times than in ordinary source size conditions. The spacial resolutions in different source size symmetry conditions are also primary analyzed based on Rayleigh criterion. The result shows that spacial resolution can be improved notably in horizontal direction by limiting horizontal source size to a nearly symmetric source size condition. Our work demonstrates that the spacial resolution and phase contrast can be promoted at the same level by source size symmetry improved, which markedly improved the imaging quality in synchrotron radiation X-ray in-line phase-contrast imaging. It will have great benefit to high-resolution X-ray in-line phase contrast imaging. The reasons of these improvements are analyzed and developments in future are also discussed.

We report a new preparative method for providing contrast through reduction in electron density that is uniquely suited for propagation-based differential x-ray phase contrast imaging. The method, which results in an air or fluid filled vasculature, makes possible visualization of the smallest microvessels, roughly down to 15 µm, in an excised murine liver, while preserving the tissue for subsequent histological workup. We show the utility of spatial frequency filtering for increasing the visibility of minute features characteristic of phase contrast imaging, and the capability of tomographic reconstruction to reveal microvessel structure and three-dimensional visualization of the sample. The effect of water evaporation from livers during x-ray imaging on the visibility of blood vessels is delineated. The deformed vascular tree in a cancerous murine liver is imaged.

The magneto-optical polarization rotation effect has myriad applications in many research areas spanning the scientific spectrum, including space and interstellar research, nanotechnology, material science, biomedical imaging, and subatomic particle research. In the nonlinear magneto-optical rotation (NMOR) effect, the angle of rotation of a linearly polarized optical field in a magnetized medium is dependent upon its intensity. However, typical NMOR signals of conventional single-beam -scheme atomic magnetometers are peculiarly small, requiring sophisticated magnetic shielding and high-frequency phase-sensitive detection. Here, we show the presence of an energy-symmetry-based propagation growth blockade that undermines the NMOR effect in conventional single-beam -scheme atomic magnetometers. We further demonstrate, both experimentally and theoretically, an inelastic wave-mixing technique that breaks this NMOR blockade, resulting in more-than-2-orders-of-magnitude enhancement of the NMOR signal power amplitude that cannot be achieved with conventional single-beam -scheme atomic magnetometers. This technique, demonstrated here with substantially reduced light intensities at near-room temperatures, may lead to many applications, especially in the field of biomagnetism and high-resolution low-field magnetic imaging.

The basic principles of x-ray image formation in radiography have remained essentially unchanged since Röntgen first discovered x-rays over a hundred years ago. The conventional approach relies on x-ray absorption as the sole source of contrast and draws exclusively on ray or geometrical optics to describe and interpret image formation. This approach ignores another, potentially more useful source of contrast, namely phase and scattering information. Phase-contrast imaging techniques, which can be understood using wave optics rather than ray optics, offer ways to augment or complement standard absorption contrast by incorporating phase information. The recent development of grating based phase- and darkfield-contrast imaging with x-rays¹ pawed the way for many potential applications to medical imaging and structure determination in material science.<br />Here we present our recent contributions to the field of interferometric phase-contrast and dark-field x-ray imaging. We introduce a new material dependent scattering parameter, the <em>Linear Diffusion Coefficient</em>, and a quantitative mathematical formalism to extend the dark-field x-ray images into three dimensions by tomographic reconstruction. Further, the results of two experiments that illustrate the potential of dark-field imaging for computed tomography are shown.

X-ray computed tomography (CT) is a powerful and routinely used clinical diagnostic technique, which is well tolerated by patients, and which provides high-resolution images and volumetric information about the body. However, two important limitations still affect this examination procedure: (1) its low sensitivity with respect to soft tissues, and (2) the hazards associated with x-ray exposure. Conventional radiology is based on the detection of the different photon absorption properties that characterize biological tissues, and thus the obtainable image contrast from soft and/or similar tissues is intrinsically limited. In this scenario, x-ray phase contrast imaging (XPCI) has been extensively tested and proven to overcome some of the main issues surrounding standard x-ray imaging. In addition to the absorption signal, XPCI relies on detecting the phase shifts induced by an object. Interestingly, as the order of magnitude of the phase contrast is higher than that of absorption, XPCI can, in principle, offer higher sensitivity at lower radiation doses. However, other technical aspects may counterbalance this gain, and an optimized setup and image processing solutions need to be implemented. The work presented here describes the strategies and developments we have realized, with the aim of controlling the radiation dose for the highly sensitive and quantitative XPCI-CT. Different algorithms for the phase retrieval and CT reconstruction of the XPCI data are presented. The CT algorithms we have implemented, namely the equally sloped tomography and the dictionary learning method, allow the image quality to be preserved while reducing the number of angular projections required by a factor of five. The results applied to breast imaging report accurate reconstructions at clinically compatible doses of the 3D distribution of the refractive properties of full human organs obtained by using three different phase retrieval methods. The described methodologies and the presented results have been validated by a team of clinical radiologists and represent an important step in the exploitation of XPCI-CT for in vivo and possible clinical applications.

For centuries, lens-based microscopy, such as optical, phase-contrast, fluorescence, confocal, and electron microscopy, has played an important role in the evolution of modern science and technology. In 1999, a novel form of microscopy, i.e., coherent diffraction imaging (also termed coherent diffraction microscopy or lensless imaging), was developed and transformed our conventional view of microscopy, in which the diffraction pattern of a noncrystalline specimen or a nanocrystal was first measured and then directly phased to obtain a high-resolution image. The well-known phase problem was solved by combining the oversampling method with iterative algorithms. In this paper, we will briefly discuss the principle of coherent diffraction imaging, present various implementation schemes of this imaging modality, and illustrate its broad applications in materials science, nanoscience, and biology. As coherent X-ray sources such as high harmonic generation and X-ray free-electron lasers are presently under rapid development worldwide, coherent diffraction imaging can potentially be applied to perform high-resolution imaging of materials/nanoscience and biological specimens at the femtosecond time scale.