Simultaneous fast scanning XRF, dark field, phase-, and absorption contrast tomography

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.

Interest in grating-based x-ray interferometry has grown rapidly in recent years, due in part to the systems ability to simultaneously provide images of multiple contrast mechanisms within a single acquisition. In addition to the well known absorption and phase contrast images, a third image of local small angle scattering known as the dark-field image is produced. There are limited published results describing applications of this method in medical imaging. In this work, the dark-field contrast mechanism is examined in the context of medical imaging. Experimental results demonstrate the relationship of both the size of the scatterers and their electron density and the resulting dark-field signal strength. The dark-field images are produced using both the well-known phase stepping technique and the recently reported moir´e technique. The results show that dark-field signal strength increases with increased difference in electron density from the background and with decreased scatterer size. They also demonstrate the equivalence of the resulting data using either signal extraction technique.

X-ray dark field signals, measurable in many x-ray phase contrast imaging (XPCI) setups, stem from unresolvable microstructures in the scanned sample. This makes them ideally suited for the detection of certain pathologies, which correlate with changes in the microstructure of a sample. Simulations of x-ray dark field signals can aid in the design and optimization of XPCI setups, and the development of new reconstruction techniques. Current simulation tools, however, require explicit modelling of the sample microstructures according to their size and spatial distribution. This process is cumbersome, does not translate well between different samples, and considerably slows down simulations. In this work, a condensed history approach to modelling x-ray dark field effects is presented, under the assumption of an isotropic distribution of microstructures, and applied to edge illumination phase contrast simulations. It substantially simplifies the sample model, can be easily ported between samples, and is two orders of magnitude faster than conventional dark field simulations, while showing equivalent results.Clinical relevance- Dark field signal provides information on the microstructure distribution within the investigated sample, which can be applied in areas such as histology and lung x-ray imaging. Efficient simulation tools for this dark field signal aid in optimizing scanning setups, acquisition schemes and reconstruction techniques.

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.

In this letter, we report results obtained with a recently developed approach for grating-based x-ray dark-field imaging [F. Pfeiffer et al., Nat. Mater. 7, 134 (2008)]. Since the image contrast is formed through the mechanism of small-angle scattering, it provides complementary and otherwise inaccessible structural information about the specimen at the micron and submicron length scales. Our approach is fully compatible with conventional transmission radiography and the grating-based hard x-ray phase-contrast imaging scheme [F. Pfeiffer et al., Nat. Phys. 2, 258 (2006)]. Since it can be used with standard x-ray tube sources, we envisage widespread applications to x-ray medical imaging, industrial nondestructive testing, or security screening.

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.

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.

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.

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.

Grating-based X-ray dark-field imaging is a novel technique for obtaining image contrast for object structures at size scales below setup resolution. Such an approach appears particularly beneficial for medical imaging and nondestructive testing. It has already been shown that the dark-field signal depends on the direction of observation. However, up to now, algorithms for fully recovering the orientation dependence in a tomographic volume are still unexplored. In this publication, we propose a reconstruction method for grating-based X-ray dark-field tomography, which models the orientation-dependent signal as an additional observable from a standard tomographic scan. In detail, we extend the tomographic volume to a tensorial set of voxel data, containing the local orientation and contributions to dark-field scattering. In our experiments, we present the first results of several test specimens exhibiting a heterogeneous composition in microstructure, which demonstrates the diagnostic potential of the method.

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 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.

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.

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.