X-ray dark-field and phase-contrast imaging using a grating interferometer

Purpose: The purpose of the present study was to evaluate if x-ray dark-field imaging can help to visualize lung cancer in mice. Materials and Methods: The experiments were performed using mutant mice with high-grade adenocarcinomas. Eight animals with pulmonary carcinoma and eight control animals were imaged in radiography mode using a prototype small-animal x-ray dark-field scanner and three of the cancerous ones additionally in CT mode. After imaging, the lungs were harvested for histological analysis. To determine their diagnostic value, x-ray dark-field and conventional attenuation images were analyzed by three experienced readers in a blind assessment. Results radiographic imaging: The lung nodules were much clearer visualized on the dark-field radiographs compared to conventional radiographs. The loss of air-tissue interfaces in the tumor leads to a significant loss of x-ray scattering, reflected in a strong dark-field signal change. The difference between tumor and healthy tissue in terms of x-ray attenuation is significantly less pronounced. Furthermore, the signal from the overlaying structures on conventional radiographs complicates the detection of pulmonary carcinoma. Results CT imaging: The very first in-vivo CT-imaging results are quite promising as smaller tumors are often better visible in the dark-field images. However the imaging quality is still quite low, especially in the attenuation images due to un-optimized scanning parameters. Conclusion: We found a superior diagnostic performance of dark-field imaging compared to conventional attenuation based imaging, especially when it comes to the detection of small lung nodules. These results support the motivation to further develop this technique and translate it towards a clinical environment.

X-ray chest radiography is an inexpensive and broadly available tool for initial assessment of the lung in clinical routine, but typically lacks diagnostic sensitivity for detection of pulmonary diseases in their early stages. Recent X-ray dark-field (XDF) imaging studies on mice have shown significant improvements in imaging-based lung diagnostics. Especially in the case of early diagnosis of chronic obstructive pulmonary disease (COPD), XDF imaging clearly outperforms conventional radiography. However, a translation of this technique towards the investigation of larger mammals and finally humans has not yet been achieved. In this letter, we present the first in-vivo XDF full-field chest radiographs (32 × 35 cm2) of a living pig, acquired with clinically compatible parameters (40 s scan time, approx. 80 µSv dose). For imaging, we developed a novel high-energy XDF system that overcomes the limitations of currently established setups. Our XDF radiographs yield sufficiently high image quality to enable radiographic evaluation of the lungs. We consider this a milestone in the bench-to-bedside translation of XDF imaging and expect XDF imaging to become an invaluable tool in clinical practice, both as a general chest X-ray modality and as a dedicated tool for high-risk patients affected by smoking, industrial work and indoor cooking.

Sample radiation damage is one of the main drawbacks limiting applications of the x-ray phase-contrast imaging method. Recently, for x-ray grating-based phase contrast imaging, the reverse projection (RP) method has been proposed by Zhu et al. [Proc. Natl. Acad. Sci. U.S.A. 107, 13576-13581 (2010)]. Compared to the conventional phase stepping technique, the RP method allows a strong reduction of the exposure time and minimization of the errors induced by mechanical vibrations. However, so far, it has only been considered for parallel beam illumination, typical of a synchrotron radiation source. In this paper, a generalization of the RP method from parallel beam geometry to fan beam geometry was presented and discussed. Within parallel beam geometry, the RP method utilizes the conjugate characteristic between reverse projection images. Nevertheless, this characteristic is not directly satisfied for fan beam geometry. In this study, a phantom composed of known materials was constructed and the projection images of the phantom were calculated in a fan beam geometry. By considering single ray, the conjugate images of the projection images were derived from the projection dataset. After that, using the modified RP method the authors retrieved phase and absorption information from paired images. Extracted phase and absorption information of the phantom were in good agreement with theoretical values. Additionally, the slice reconstruction was performed and the results turned out to be in the authors' expectation. Theoretical calculations and numerical simulations confirm both feasibility and validity of the RP method under fan beam illumination. Because this method is simple, fast, and releases a relatively low dose, the authors believe that this research is very useful for the x-ray phase contrast imaging applications in clinical diagnosis, bioresearch, and industrial nondestructive testing.

In the past few years, X-ray phase-contrast and dark-field imaging have evolved to be invaluable tools for non-destructive sample visualisation, delivering information inaccessible by conventional absorption imaging. X-ray phase-sensing techniques are furthermore increasingly used for at-wavelength metrology and optics characterisation. One of the latest additions to the group of differential phase-contrast methods is the X-ray speckle-based technique. It has drawn significant attention due to its simple and flexible experimental arrangement, cost-effectiveness and multimodal character, amongst others. Since its first demonstration at highly brilliant synchrotron sources, the method has seen rapid development, including the translation to polychromatic laboratory sources and extension to higher-energy X-rays. Recently, different advanced acquisition schemes have been proposed to tackle some of the main limitations of previous implementations. Current applications of the speckle-based method range from optics characterisation and wavefront measurement to biomedical imaging and materials science. This review provides an overview of the state of the art of the X-ray speckle-based technique. Its basic principles and different experimental implementations as well as the the latest advances and applications are illustrated. In the end, an outlook for anticipated future developments of this promising technique is given.

Scanning hard X-ray nanoprobe imaging provides a unique tool for probing specimens with high sensitivity and large penetration depth. Moreover, the combination of complementary techniques such as X-ray fluorescence, absorption, phase contrast and dark field imaging gives complete quantitative information on the sample structure, composition and chemistry. The multi-technique “FLYSCAN” data acquisition scheme developed at Synchrotron SOLEIL permits to perform fast continuous scanning imaging and as such makes scanning tomography techniques feasible in a time-frame well-adapted to typical user experiments. Here we present the recent results of simultaneous fast scanning multi-technique tomography performed at Soleil. This fast scanning scheme will be implemented at the Nanoscopium beamline for large field of view 2D and 3D multimodal imaging.

X-ray dark-field and phase-contrast imaging using near-field speckles is a novel technique that overcomes limitations inherent in conventional absorption x-ray imaging, i.e. poor contrast for features with similar density. Speckle-based imaging yields a wealth of information with a simple setup tolerant to polychromatic and divergent beams, and simple data acquisition and analysis procedures. Here, we present a simulation software used to model the image formation with the speckle-based technique, and we compare simulated results on a phantom sample with experimental synchrotron data. Thorough simulation of a speckle-based imaging experiment will help for better understanding and optimising the technique itself.

Phase contrast and dark-field imaging are relatively new X-ray imaging modalities that provide additional information to conventional attenuation-based imaging. However, this new information comes at the price of a more complex acquisition scheme and optical components. Among the different techniques available, such as grating interferometry or edge illumination, modulation-based and more generally single-mask/grid imaging techniques simplify these new procedures to obtain phase and dark-field images by shifting the experimental complexity to the numerical post-processing side. This family of techniques involves inserting a membrane into the X-ray beam that locally modulates the intensity to create a pattern on the detector which serves as a reference. However, the topological nature of the mask used seems to determine the quality of the reconstructed phase and dark-field images. We present in this article an in-depth study of the impact of the membrane parameters used in a single-mask imaging approach. A spiral topology seems to be an optimum both in terms of resolution and contrast-to-noise ratio compared with random and regular patterns.

X-ray imaging has conventionally relied upon attenuation to provide contrast. In recent years, two complementary modalities have been added; (a) phase contrast, which can capture low-density samples that are difficult to see using attenuation, and (b) dark-field x-ray imaging, which reveals the presence of sub-pixel sample structures. These three modalities can be accessed using a crystal analyser, a grating interferometer or by looking at a directly-resolved grid, grating or speckle pattern. Grating and grid-based methods extract a differential phase signal by measuring how far a feature in the illumination has been shifted transversely due to the presence of a sample. The dark-field signal is extracted by measuring how the visibility of the structured illumination is decreased, typically due to the presence of sub-pixel structures in a sample. The strength of the dark-field signal may depend on the grating period, the pixel size and the set-up distances, and additional dark-field signal contributions may be seen as a result of strong phase effects or other factors. In this paper we show that the finite-difference form of the Fokker–Planck equation can be applied to describe the drift (phase signal) and diffusion (dark-field signal) of the periodic or structured illumination used in phase contrast x-ray imaging with gratings, in order to better understand any cross-talk between attenuation, phase and dark-field x-ray signals. In future work, this mathematical description could be used as a basis for new approaches to the inverse problem of recovering both phase and dark-field information.

A key contribution to X-ray dark-field (XDF) contrast is the diffusion of X-rays by sample structures smaller than the imaging system's spatial resolution; this is related to position-dependent small-angle X-ray scattering. However, some experimental XDF techniques have reported that XDF contrast is also generated by resolvable sample edges. Speckle-based X-ray imaging (SBXI) extracts the XDF by analyzing sample-imposed changes to a reference speckle pattern's visibility. We present an algorithm for SBXI (a variant of our previously developed multimodal intrinsic speckle-tracking (MIST) algorithm) capable of separating these two physically different XDF contrast mechanisms. The algorithm uses what we call the devolving Fokker-Planck equation for paraxial X-ray imaging as its forward model and then solves the associated multimodal inverse problem to retrieve the attenuation, phase, and XDF properties of the sample. Previous MIST variants were based on the evolving Fokker-Planck equation, which considers how a reference-speckle image is modified by the introduction of a sample. The devolving perspective instead considers how the image collected in the presence of the sample and the speckle membrane optically flows in reverse to generate the reference-speckle image when the sample is removed from the system. We compare single- and multiple-exposure multimodal retrieval algorithms from the two Fokker-Planck perspectives. We demonstrate that the devolving perspective can distinguish between two physically different XDF contrast mechanisms, namely, unresolved microstructure- and sharp-edge-induced XDF. This was verified by applying the different retrieval algorithms to two experimental data sets - one phantom sample and one organic sample. We anticipate that this work will be useful in (1) yielding a pair of complementary XDF images that separate sharp-edge diffuse scatter from diffuse scatter due to spatially random unresolved microstructure, (2) XDF computed tomography, where the strong edge XDF signal can lead to strong contaminating streaking artefacts, and (3) sample preparation, as samples will not need to be embedded since the strong XDF edge signal seen between the sample and air can be separated out.

Grating-based x-ray phase-contrast imaging is a fast developing new modality not only for medical imaging, but as well for other fields such as material sciences. While these many possible applications arise, the knowledge of the noise behavior is essential. In this work, the authors used a least squares fitting algorithm to calculate the noise behavior of the three quantities absorption, differential phase, and dark-field image. Further, the calculated error formula of the differential phase image was verified by measurements. Therefore, a Talbot interferometer was setup, using a microfocus x-ray tube as source and a Timepix detector for photon counting. Additionally, simulations regarding this topic were performed. It turned out that the variance of the reconstructed phase is only dependent of the total number of photons used to generate the phase image and the visibility of the experimental setup. These results could be evaluated in measurements as well as in simulations. Furthermore, the correlation between absorption and dark-field image was calculated. These results provide the understanding of the noise characteristics of grating-based phase-contrast imaging and will help to improve image quality.

Mineral building materials suffer from weathering processes such as salt efflorescence, freeze–thaw cycling, and microbial colonization. All of these processes are linked to water (liquid and vapor) in the pore space. The degree of damage following these processes is heavily influenced by pore space properties such as porosity, pore size distribution, and pore connectivity. X-ray computed micro-tomography (µCT) has proven to be a valuable tool to non-destructively investigate the pore space of stone samples in 3D. However, a trade-off between the resolution and field-of-view often impedes reliable conclusions on the material’s properties. X-ray dark-field imaging (DFI) is based on the scattering of X-rays by sub-voxel-sized features, and as such, provides information on the sample complementary to that obtained using conventional µCT. In this manuscript, we apply X-ray dark-field tomography for the first time on four mineral building materials (quartzite, fired clay brick, fired clay roof tile, and carbonated mineral building material), and investigate which information the dark-field signal entails on the sub-resolution space of the sample. Dark-field tomography at multiple length scale sensitivities was performed at the TOMCAT beamline of the Swiss Light Source (Villigen, Switzerland) using a Talbot grating interferometer. The complementary information of the dark-field modality is most clear in the fired clay brick and roof tile; quartz grains that are almost indistinguishable in the conventional µCT scan are clearly visible in the dark-field owing to their low dark-field signal (homogenous sub-voxel structure), whereas the microporous bulk mass has a high dark-field signal. Large (resolved) pores on the other hand, which are clearly visible in the absorption dataset, are almost invisible in the dark-field modality because they are overprinted with dark-field signal originating from the bulk mass. The experiments also showed how the dark-field signal from a feature depends on the length scale sensitivity, which is set by moving the sample with respect to the grating interferometer.

Phase-Contrast Tomography (PCT) is becoming an important technique for nondestructive, in-situ characterization of soft and hard condensed matter. This thesis sheds light on our progress in developing novel tomographic reconstruction algorithms in combination with in-situ experimental approaches that employ propagation-based PCT. These developments are aimed to improve the spatial and temporal resolutions of in-situ studies of the soft and hard condensed matter. The mechanical properties of materials such as steel are, to a large extent, defined by its microstructure. Propagation-based PCT (i.e. holotomography) can be used to visualize the microstructures associated with small variations in density or composition in the bulk of the specimen. This imaging technique has the advantage of being non-destructive and allows to carry out in-situ, time-resolved observations of miscrostructural changes during dynamic processes such as solid-state phase transformations. Sufficient spatial and temporal resolution can be achieved only when an extremely bright x-ray source is used. In order to test whether a novel table-top x-ray source, the MIRRORCLE-6X, can be used for implementation of a propagation-based PCT system, we have carried out a series of experiments. The characteristics of a propagation-based PCI system that employs the MIRRORCLE-6X were analyzed. In our further research we have focused on the experiments that could be performed at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. We reported on the investigation of the cementite microstructure in carbon steel. In this work we present the reconstruction of the three-dimensional morphology of cementite grains in the bulk of steel using a non-destructive imaging technique – x-ray Phase-Contrast Tomography (PCT). Complementary information about the crystalline structure of the ferrite grains surrounding the cementite is obtained using x-ray Diffraction-Contrast Tomography (DCT). The work was continued by a time-resolved x-ray PCT investigation of the austenite grain growth during the ferrite-to-austenite phase transformation in low-carbon steel. Experimental data allows to visualize the evolution of the three-dimensional morphology of the austenite-ferrite interfaces with a spatial resolution on the order of 1 ?m and a time resolution of less than 9 minutes. The in-situ measurements show that the theory for grain growth during diffusional solid-state phase transformations needs to be extended in order to describe the drastically lower mobility that we observed for flat interfaces compared to curved interfaces. We observe that some flat interfaces are completely immobile, which is not predicted by the state-of-the-art theories and showed - for the first time - that new computational model for grain growth are needed. Quantitative image reconstruction based on PCT data requires solving two inverse problems: phase retrieval and tomographic reconstruction. In most cases, the problem of phase retrieval is ill-posed and requires that some type of a prior knowledge about the reconstructed image (i.e. particular regularization method) is used. We present a novel algebraic approach suitable for phase retrieval using various linear models. In this approach Total Variation (TV) minimization is used for regularization of the linearized inverse problem by promoting the solution with a sparse gradient magnitude (i.e. piece-wise constant solution). In that case prior knowledge about the reconstructed image may allow to (partially) recover the unknown spatial frequencies that are undefined by the experimental data. The problem of tomographic reconstruction based on PCT data can be solved using a similar approach. We conclude our investigation of the image reconstruction algorithms by introducing several algebraic approaches suitable for tomographic reconstruction based on PCT data. In these approaches TV minimization is used to find a regularized solution to an underdetermined linear system based on a linearized representation of the PCT. When the density of the reconstructed object is piece-wise constant (or close to it) a virtually artifact-free solution can be computed for the tomographic problem. The proposed approach can also be used to radically improve the accuracy of the tomographic reconstruction based on incomplete data (e.g. small number of projections) or data with low signal to noise ratio.

X-ray dark-field imaging using a grating interferometer has shown potential benefits for a variety of applications in recent years. X-ray dark-field image is commonly retrieved by using discrete Fourier transform from the acquired phase-stepping data. The retrieval process assumes a constant phase step size and a constant flux for each stepped grating position. However, stepping errors and flux fluctuations inevitably occur due to external vibrations and/or thermal drift during data acquisition. Previous studies have shown that those influences introduce errors in the acquired phase-stepping data, which cause obvious moiré artifacts in the retrieved refraction image. This work investigates moiré artifacts in x-ray dark-field imaging as a result of flux fluctuations. For the retrieved mean intensity, amplitude, visibility and dark-field images, the dependence of moiré artifacts on flux fluctuation factors is theoretically derived respectively by using a first-order Taylor series expansion. Results of synchrotron radiation experiments verify the validity of the derived analytical formulas. The spatial frequency characteristics of moiré artifacts are analyzed and compared to those induced by phase-stepping errors. It illustrates that moiré artifacts can be estimated by a weighted mean of flux fluctuation factors, with the weighting factors dependent on the moiré phase and different greatly for each retrieved image. Furthermore, moiré artifacts can even be affected by object’s features not displayed in the particular contrast. These results can be used to interpret images correctly, identify sources of moiré artifacts, and develop dedicated algorithms to remove moiré artifacts in the retrieved multi-contrast images.

Field size of 80 mm ×80 mm for X-ray dark-field (DFI) imaging at 35 keV using a 2.16-mm-thick 440 Laue diffraction analyzer has been achieved. Under this condition, only refracted X-rays from sample can transmit through this filter to form DFI while the beam that has not changed its direction is repelled to the diffraction direction. Its spatial resolution is 10 microns or better. An excised human femoral head in a water-filled vinyl bag simulating a clinical condition shows a high-contrast and high-spatial-resolution articular cartilage that has not been visualized by X-ray technique

X-ray phase contrast imaging (PCI) provides excellent image contrast by utilizing the phase shift. The introduction of microbubbles into tissues can cause a phase shift to make microbubbles visibly identified on PCI. In this study, we assessed the feasibility of targeted microbubble-based PCI for the detection of thrombosis. The absorption and phase contrast images of P-selectin-targeted microbubbles (MBP) were obtained and compared in vitro. MBP, control IgG-targeted microbubbles (MBC), and unbound microbubbles (MBU) were tested for binding specificity on thrombi expressing P-selectin. MBP were used as molecular PCI probes to evaluate P-selectin expression in a mouse model of arteriovenous shunt thrombosis that was created using PE tubes in the bypass outside of the mouse body. PCI clearly showed the microbubbles not viewable via absorption contrast imaging (ACI). In vitro attachment of MBP (91.60 ± 11.63) to thrombi was significantly higher than attachment of MBC (17.80 ± 4.02, P < 0.001) or MBU (9.80 ± 2.59, P < 0.001). In the mouse model of arteriovenous shunt thrombosis, the binding affinity of MBP (15.50 ± 6.25) was significantly greater than that of MBC (0.50 ± 0.84, P < 0.001) or MBU (0.33 ± 0.52, P < 0.001). Our results indicate that molecular PCI may be considered as a novel and promising imaging modality for the investigation of thrombosis. • Small thrombi are rarely detected by conventional radiography. • Phase contrast imaging (PCI) provides higher contrast and spatial resolution than conventional radiography. • P-selectin targeted microbubbles detected by PCI may suggest early thrombosis.