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As a very fast and non-invasive examination, conventional X-ray radiography is well established as the first line diagnostic imaging method of the human bone system. While major bone injuries such as fractures and dislocations are usually easily detectable on conventional X-ray images, more subtle injuries such as microfractures are often missed, leading to mistreatment and potential long-term consequences. The technology of Photon-Counting Dual-Energy Radiography (PCDER) yields the possibility to decompose conventional X-ray images into basis material images such as bone- and soft-tissue-equivalence images. The obtained basis material images offer significant advantages in terms of image contrast and image details over the raw attenuation image which shows an overlap of bone and soft tissue. Whereas the advantages of bone- and soft-tissue-equivalence images have been broadly discussed referring to bone subtraction images in the detection of pulmonary diseases, this method has not been considered for the analysis of musculoskeletal images until present. In this study we show that basis component equivalence images have high potential to improve the diagnostic accuracy of the detection of minor bone lesions during clinical trauma imaging. A reader study performed by three experienced radiologists compares the image quality of basis material images to a standard radiograph image of a non-fractured cadaveric hand.

Objective: The aim of this study was to evaluate the potential of x-ray dark-field radiography for the noninvasive detection of monosodium urate (MSU) crystals as a novel diagnostic tool for gout., Materials and Methods: Contrast-to-noise ratios of MSU crystals in conventional radiography and dark-field radiography have been compared in a proof of principle measurement. Monosodium urate crystals have been injected into mouse legs in an ex vivo experimental gout setup. Three radiologists independently evaluated the images for the occurrence of crystal deposits in a blinded study for attenuation images only, dark-field images only, and with both images available for a comprehensive diagnosis. All imaging experiments have been performed at an experimental x-ray dark-field setup with a 3-grating interferometer, a rotating anode tube (50 kVp), and a photon-counting detector (effective pixel size, 166 μm)., Results: X-ray dark-field radiography provided a strong signal increase for MSU crystals in a physiological buffer solution compared with conventional attenuation radiography with a contrast-to-noise ratio increase from 0.8 to 19.3. Based on conventional attenuation images only, the reader study revealed insufficient diagnostic performance (sensitivity, 11%; specificity, 92%) with poor interrater agreement (Cohen's coefficient κ = 0.031). Based on dark-field images, the sensitivity increased to 100%, specificity remained at 92%, and the interrater agreement increased to κ = 0.904. Combined diagnosis based on both image modalities maximized both sensitivity and specificity to 100% with absolute interrater agreement (κ = 1.000)., Conclusions: X-ray dark-field radiography enables the detection of MSU crystals in a mouse-based gout model. The simultaneous avaliability of a conventional attenuation image together with the dark-field image provides excellent detection rates of gout deposits with high specificity.

This study investigates the x-ray scattering characteristics of microsphere particles in x-ray-grating-based interferometric imaging at different concentrations, bubble sizes and tube voltages (kV). Attenuation (ATI), dark-field (DFI) and phase-contrast (PCI) images were acquired. Signal-to-noise (SNR) and contrast-to-noise ratios with water (CNR w ) and air as reference (CNR a ) were determined. In all modalities, a linear relationship between SNR and microbubbles concentration, respectively, microsphere size was found. A significant gain of SNR was found when varying kV. SNR was significantly higher in DFI and PCI than ATI. The highest gain of SNR was shown at 60 kV for all media in ATI and DFI, at 80 kV for PCI. SNR for all media was significantly higher compared to air and was slightly lower compared to water. A linear relationship was found between CNR a , CNR w , concentration and size. With increasing concentration and decreasing size, CNR a and CNR w increased in DFI, but decreased in PCI. Best CNR a and CNR w was found at specific combination of kV and concentration/size. Highest average CNR a and CNR w was found for microspheres in ATI and PCI, for microbubbles in DFI. Microspheres are a promising contrast-media for grating-based-interferometry, if kV, microsphere size and concentration are appropriately combined.

Spectral and grating-based differential phase-contrast (DPC) x-ray imaging are two emerging technologies that offer additional information compared with conventional attenuation-based x-ray imaging. In the case of spectral imaging, energy-resolved measurements allow the generation of material-specific images by exploiting differences in the energy-dependent attenuation. DPC imaging uses the phase shift that an x-ray wave exhibits when traversing an object as contrast generation mechanism. Recently, we have investigated the combination of these two imaging techniques (spectral DPC imaging) and demonstrated potential advantages compared with spectral imaging. In this work, we present a noise analysis framework that allows the prediction of (co-) variances and noise power spectra for all three imaging methods. Moreover, the optimum acquisition parameters for a particular imaging task can be determined. We use this framework for a performance comparison of all three imaging methods. The comparison is focused on (projected) electron density images since they can be calculated with all three imaging methods. Our study shows that spectral DPC imaging enables the calculation of electron density images with strongly reduced noise levels compared with the other two imaging methods for a large range of clinically relevant pixel sizes. In contrast to conventional DPC imaging, there are no long-range noise correlations for spectral DPC imaging. This means that excessive low frequency noise can be avoided. We confirm the analytical predictions by numerical simulations.

We investigate the combination of two emerging X-ray imaging technologies, namely spectral imaging and differential phase contrast imaging. By acquiring spatially and temporally registered images with several different X-ray spectra, spectral imaging can exploit differences in the energy-dependent attenuation to generate material selective images. Differential phase contrast imaging uses an entirely different contrast generation mechanism: The phase shift that an X-ray wave exhibits when traversing an object. As both methods can determine the (projected) electron density, we propose a novel material decomposition algorithm that uses the spectral and the phase contrast information simultaneously. Numerical experiments show that the combination of these two imaging techniques benefits from the strengths of the individual methods while the weaknesses are mitigated: Quantitatively accurate basis material images are obtained and the noise level is strongly reduced, compared to conventional spectral X-ray imaging.

Since their discovery by Wilhelm Conrad Röntgen in 1895, X-rays have become the most widely available, typically fastest, and usually most cost-effective medical imaging modality today. From the early radiographic approaches using X-ray films as detectors, the portfolio of medical X-ray imaging devices developed into a large range of dedicated instrumentation for various applications. While X-ray imaging has come a long way, there are some physical properties of X-rays, which have not yet been fully exploited, and which may offer quite some room for further enhancements of current X-ray imaging equipment. Firstly, X-ray imaging today is mainly black and white, despite the fact that X-ray generators actually create a full spectrum of X-ray energies, and that the interactions of X-rays that occur within the human body are not the same for all energies and every material. Exploiting these spectral dependencies allows to not only obtain a black and white CT image, but also to obtain more molecularly specific information, which is relevant particularly in oncological precision radiology. The second aspect of X-rays, and so far in radiology mainly neglected and unused, is the physical fact that X-rays can also be interpreted in the wave picture, and not only as presently been done in the particle picture. If interpreted as waves, X-rays-just like visible light-experience a phase shift in matter, and this-if exploited correctly-can produce a new class of X-ray images, which then depict the wave interactions of X-rays with matter, rather than only the attenuating properties, as done until now.

Small-animal physiology studies are typically complicated, but the level of complexity is greatly increased when performing live-animal X-ray imaging studies at synchrotron and compact light sources. This group has extensive experience in these types of studies at the SPring-8 and Australian synchrotrons, as well as the Munich Compact Light Source. These experimental settings produce unique challenges. Experiments are always performed in an isolated radiation enclosure not specifically designed for live-animal imaging. This requires equipment adapted to physiological monitoring and test-substance delivery, as well as shuttering to reduce the radiation dose. Experiment designs must also take into account the fixed location, size and orientation of the X-ray beam. This article describes the techniques developed to overcome the challenges involved in respiratory X-ray imaging of live animals at synchrotrons, now enabling increasingly sophisticated imaging protocols., (open access.)

Conventional x-ray radiography is a well-established standard in diagnostic imaging of human bones. It reveals typical bony anatomy with a strong surrounding cortical bone and trabecular structure of the inner part. However, due to limited spatial resolution, x-ray radiography cannot provide information on the microstructure of the trabecular bone. Thus, microfractures without dislocation are often missed in initial radiographs, resulting in a lack or delay of adequate therapy. Here we show that x-ray vector radiography (XVR) can overcome this limitation and allows for a deeper insight into the microstructure with a radiation exposure comparable to standard radiography. XVR senses x-ray ultrasmall-angle scattering in addition to the attenuation contrast and thereby reveals the mean scattering strength, its degree of anisotropy and the orientation of scattering structures. Corresponding to the structural characteristics of bones, there is a homogenous mean scattering signal of the trabecular bone but the degree of anisotropy is strongly affected by variations in the trabecular structure providing more detailed information on the bone microstructure. The measurements were performed at the Munich Compact Light Source, a novel type of x-ray source based on inverse Compton scattering. This laboratory-sized source produces highly brilliant quasi-monochromatic x-rays with a tunable energy.

Accounting for about 1.5 million deaths annually, lung cancer is the prevailing cause of cancer deaths worldwide, mostly associated with long-term smoking effects. Numerous small-animal studies are performed currently in order to better understand the pathogenesis of the disease and to develop treatment strategies. Within this letter, we propose to exploit X-ray dark-field imaging as a novel diagnostic tool for the detection of lung cancer on projection radiographs. Here, we demonstrate in living mice bearing lung tumors, that X-ray dark-field radiography provides significantly improved lung tumor detection rates without increasing the number of false-positives, especially in the case of small and superimposed nodules, when compared to conventional absorption-based imaging. While this method still needs to be adapted to larger mammals and finally humans, the technique presented here can already serve as a valuable tool in evaluating novel lung cancer therapies, tested in mice and other small animal models.

Objective: The aim of this study was to evaluate the diagnostic value of x-ray dark-field imaging in projection radiography-based depiction of pneumothoraces in the neonatal murine lung, a potentially life-threatening medical condition that requires a timely and correct diagnosis., Materials and Methods: By the use of a unique preclinical model, 7-day-old C57Bl/6N mice received mechanical ventilation for 2 or 8 hours with oxygen-rich gas (FIO2 = 0.4; n = 24). Unventilated mice either spontaneously breathed oxygen-rich gas (FIO2 = 0.4) for 2 or 8 hours or room air (n = 22). At the end of the experiment, lungs were inflated with a standardized volume of air after a lethal dose of pentobarbital was administered to the pups. All lungs were imaged with a prototype grating-based small-animal scanner to acquire x-ray transmission and dark-field radiographs. Image contrast between the air-filled pleural space and lung tissue was quantified for both transmission and dark-field radiograms. After the independent expert's assessment, 2 blinded readers evaluated all dark-field and transmission images for the presence or absence of pneumothoraces. Contrast ratios, diagnostic accuracy, as well as reader's confidence and interreader agreement were recorded for both imaging modalities., Results: Evaluation of both x-ray transmission and dark-field radiographs by independent experts revealed the development of a total of 10 pneumothoraces in 8 mice. Here, the contrast ratio between the air-filled pleural space of the pneumothoraces and the lung tissue was significantly higher in the dark field (8.4 ± 3.5) when compared with the transmission images (5.1 ± 2.8; P < 0.05). Accordingly, the readers' diagnostic confidence for the diagnosis of pneumothoraces was significantly higher for dark-field compared with transmission images (P = 0.001). Interreader agreement improved from moderate for the analysis of transmission images alone (κ = 0.41) to very good when analyzing dark-field images alone (κ = 0.90) or in combination with transmission images (κ = 0.88). Diagnostic accuracy significantly improved for the analysis of dark-field images alone (P = 0.04) or in combination with transmission images (P = 0.02), compared with the analysis of transmission radiographs only., Conclusions: The significant improvement in contrast ratios between lung parenchyma and free air in the dark-field images allows the facilitated detection of pneumothoraces in the newborn mouse. These preclinical experiments indicate the potential of the technique for future clinical applications.

Grating based X-ray differential phase contrast imaging (DPCI) allows for high contrast imaging of materials with similar absorption characteristics. In the last years' publications, small animals or parts of the human body like breast, hand, joints or blood vessels have been studied. Larger objects could not be investigated due to the restricted field of view limited by the available grating area. In this paper, we report on a new stitching method to increase the grating area significantly: individual gratings are merged on a carrier substrate. Whereas the grating fabrication process is based on the LIGA technology (X-ray lithography and electroplating) different cutting and joining methods have been evaluated. First imaging results using a 2×2 stitched analyzer grating in a Talbot-Lau interferometer have been generated using a conventional polychromatic X-ray source. The image quality and analysis confirm the high potential of the stitching method to increase the field of view considerably.

In this review article we describe the development of grating-based X-ray phase-contrast imaging, with particular emphasis on potential biomedical applications of the technology. We review the basics of image formation in grating-based phase-contrast and dark-field radiography and present some exemplary multimodal radiography results obtained with laboratory X-ray sources. Furthermore, we discuss the theoretical concepts to extend grating-based multimodal radiography to quantitative transmission, phase-contrast, and dark-field scattering computed tomography., (Copyright © 2013. Published by Elsevier GmbH.)

Purpose: To assess whether grating-based X-ray dark-field imaging can increase the sensitivity of X-ray projection images in the diagnosis of pulmonary emphysema and allow for a more accurate assessment of emphysema distribution., Materials and Methods: Lungs from three mice with pulmonary emphysema and three healthy mice were imaged ex vivo using a laser-driven compact synchrotron X-ray source. Median signal intensities of transmission (T), dark-field (V) and a combined parameter (normalized scatter) were compared between emphysema and control group. To determine the diagnostic value of each parameter in differentiating between healthy and emphysematous lung tissue, a receiver-operating-characteristic (ROC) curve analysis was performed both on a per-pixel and a per-individual basis. Parametric maps of emphysema distribution were generated using transmission, dark-field and normalized scatter signal and correlated with histopathology., Results: Transmission values relative to water were higher for emphysematous lungs than for control lungs (1.11 vs. 1.06, p<0.001). There was no difference in median dark-field signal intensities between both groups (0.66 vs. 0.66). Median normalized scatter was significantly lower in the emphysematous lungs compared to controls (4.9 vs. 10.8, p<0.001), and was the best parameter for differentiation of healthy vs. emphysematous lung tissue. In a per-pixel analysis, the area under the ROC curve (AUC) for the normalized scatter value was significantly higher than for transmission (0.86 vs. 0.78, p<0.001) and dark-field value (0.86 vs. 0.52, p<0.001) alone. Normalized scatter showed very high sensitivity for a wide range of specificity values (94% sensitivity at 75% specificity). Using the normalized scatter signal to display the regional distribution of emphysema provides color-coded parametric maps, which show the best correlation with histopathology., Conclusion: In a murine model, the complementary information provided by X-ray transmission and dark-field images adds incremental diagnostic value in detecting pulmonary emphysema and visualizing its regional distribution as compared to conventional X-ray projections.

We introduce a novel x-ray imaging approach that yields information about the local texture of structures smaller than the image pixel resolution inside an object. The approach is based on a recently developed x-ray dark-field imaging technique, using scattering from sub-micron structures in the sample. We show that the method can be used to determine the local angle and degree of orientation of bone, and fibers in a leaf. As the method is based on the use of a conventional x-ray tube we believe that it can have a great impact on medical diagnostics and non-destructive testing applications.

We report on the application of the PILATUS 100K pixel detector for medical imaging. Experimental results are presented in the form of X-ray radiographs using standard X-ray absorption contrast and a recently developed phase contrast imaging method. The results obtained with the PILATUS detector are compared to results obtained with a conventional X-ray imaging system consisting of an X-ray scintillation screen, lens optics, and a charge coupled device. Finally, the results for both systems are discussed more quantitatively based on an image power spectrum analysis.

In x-ray radiography, particularly for technical and industrial applications, a scanning setup is very often favorable when compared to a direct two-dimensional image acquisition. Here, we report on an efficient scanning method for grating based x-ray phase contrast imaging with tube based sources. It uses multiple line detectors for staggered acquisition of the individual phase-stepping images. We find that the total exposure time does not exceed the time needed in an equivalent scanning setup for absorption radiography. Therefore, we conclude that it should be possible to implement the method into a scanning system without affecting the scanning speed or significant increase in cost but with the advantage of providing both the phase contrast and the absorption information at once.

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Purpose: The authors present initial progress toward a clinically compatible x-ray phase contrast CT system, using glancing-angle x-ray grating interferometry to provide high contrast soft tissue images at estimated by computer simulation dose levels comparable to conventional absorption based CT. Methods: DPC-CT scans of a joint phantom and of soft tissues were performed in order to answer several important questions from a clinical setup point of view. A comparison between high and low fringe visibility systems is presented. The standard phase stepping method was compared with sliding window interlaced scanning. Using estimated dose values obtained with a Monte-Carlo code the authors studied the dependence of the phase image contrast on exposure time and dose. Results: Using a glancing angle interferometer at high x-ray energy (∼45 keV mean value) in combination with a conventional x-ray tube the authors achieved fringe visibility values of nearly 50%, never reported before. High fringe visibility is shown to be an indispensable parameter for a potential clinical scanner. Sliding window interlaced scanning proved to have higher SNRs and CNRs in a region of interest and to also be a crucial part of a low dose CT system. DPC-CT images of a soft tissue phantom at exposures in the range typical for absorption based CT of musculoskeletal extremities were obtained. Assuming a human knee as the CT target, good soft tissue phase contrast could be obtained at an estimated absorbed dose level around 8 mGy, similar to conventional CT. Conclusions: DPC-CT with glancing-angle interferometers provides improved soft tissue contrast over absorption CT even at clinically compatible dose levels (estimated by a Monte-Carlo computer simulation). Further steps in image processing, data reconstruction, and spectral matching could make the technique fully clinically compatible. Nevertheless, due to its increased scan time and complexity the technique should be thought of not as replacing, but as complimentary to conventional CT, to be used in specific applications. [ABSTRACT FROM AUTHOR]

Abstract: We report on a method for tomographic phase contrast imaging of centimeter sized objects. As opposed to existing techniques, our approach can be used with low-brilliance, lab based X-ray sources and thus is of interest to a wide range of applications in medicine, biology, and non-destructive testing. The work is based on the recent development of a hard X-ray grating interferometer, which has been demonstrated to yield differential phase contrast projection images. Here we particularly focus on how this method can be used for tomographic reconstructions using filtered backprojection algorithms to yield quantitative volumetric information of the real part of the samples''s refractive index. [Copyright &y& Elsevier]

Novel radiography approaches based on the wave nature of x-rays when propagating through matter have a great potential for improved future x-ray diagnostics in the clinics. Here, we present a significant milestone in this imaging method: in-vivo multi-contrast x-ray imaging of a mouse using a compact scanner. Of particular interest is the enhanced contrast in regions related to the respiratory system, indicating a possible application in diagnosis of lung diseases (e.g. emphysema). [ABSTRACT FROM AUTHOR]

X-ray Vector Radiography (XVR) is an imaging technique that reveals the orientations of sub-pixel sized structures within a sample. Several dark-field radiographs are acquired by rotating the sample around the beam propagation direction and stepping one of the gratings to several positions for every pose of the sample in an X-ray grating interferometry setup. In this letter, we present a method of performing XVR of a continuously moving sample without the need of any grating motion. We reconstruct the orientations within a sample by analyzing the change in the background moire fringes caused by the sample moving and simultaneously rotating in plane (trochoidal trajectory) across the detector field-of-view. Avoiding the motion of gratings provides significant advantages in terms of stability and repeatability, while the continuous motion of the sample makes this kind of system adaptable for industrial applications such as the scanning of samples on a conveyor belt. Being the first step in the direction of utilizing advanced sample trajectories to replace grating motion, this work also lays the foundations for a full three dimensional reconstruction of scattering function without grating motion. [ABSTRACT FROM AUTHOR]

Abstract: An interferometric technique for hard X-rays is presented. It is based on two transmission gratings and a phase-stepping technique, and it provides separate radiographs of the phase and absorption profiles of bulk samples. Tomographic reconstruction yields quantitative three-dimensional maps of the X-ray refractive index and of the attenuation coefficient, with a spatial resolution down to a few microns. The method is mechanically robust, it requires little monochromaticity, and can be scaled up to large fields of view. These are important prerequisites for use with laboratory X-ray sources. Numerous applications ranging from wave front sensing to medical radiography are presently under investigation. [Copyright &y& Elsevier]

Short glass and carbon fiber reinforced polymer composites are used in many industrial fields such as in automotive and consumers industry. Their physical and mechanical properties are often superior to those of unfilled polymer components. One aspect being of utmost importance for these properties is the fiber orientation distribution. Here, we present X-ray vector radiography as a method to characterize fiber orientation in short fiber reinforced polymer components. The method is based on X-ray grating interferometry and takes advantage of X-ray scattering caused by the sample's microstructure. Therefore, micro-structural properties can be probed nondestructively without the need for high spatial resolution. Compared to standard X-ray imaging techniques, currently applied for fiber orientation studies, the presented method does not restrict the size of the sample under investigation and allows for much shorter measurement times. In contrast to existing methods, X-ray vector radiography allows the characterization of carbon fiber reinforced polymers despite the weak attenuation contrast between the fibers and the polymer matrix. As this method is also extendable into three dimensions it is a very attractive tool for complex component geometries and carries potential to be applied to materials other than short fiber reinforced polymers. [ABSTRACT FROM AUTHOR]

Novel X-ray imaging methods expand conventional attenuation-based X-ray radiography by the phase- and the dark-field contrasts. While weakly absorbing structures in the specimen can be better visualized in phase contrast, the dark-field contrast provides information about morphological sub-pixel microstructures. Here we report an application of dark-field X-ray radiography for imaging the time-resolved setting process in fresh cement. Our results demonstrate that the microstructural changes within the cement result in a decreasing dark-field signal. We quantify this imaging signal with a time-dependent dark-field scatter coefficient and show its good correlation with the compressional wave velocity. We further present images based on a pixel-wise analysis of the scattering signal and a corresponding logistic fit. These images emphasize the benefit of dark-field imaging of cementitious materials as it provides two dimensional spatial information on the processes within the sample while other established testing techniques only provide information on the bulk average. [ABSTRACT FROM AUTHOR]

Here we report on a mathematical description for the neutron dark-field image (DFI) contrast based on the influence of the thickness-dependent beam broadening caused by scattering interactions and multiple refraction in the sample. We conduct radiography experiments to verify that the DFI signal exponentially decays as a function of thickness for both magnetic and nonmagnetic materials. Here we introduce a material-dependent parameter, the so-called linear diffusion coefficient Ω. This allows us to perform a quantitative DFI-computed tomography. Additionally, we conduct correlative small-angle neutron-scattering experiments and validate the mathematical assumption that the angular broadening of the direct beam is proportional to the square root of the number of discrete layers. [ABSTRACT FROM AUTHOR]

Abstract: We have developed a method for X-ray phase contrast imaging, which is based on a grating interferometer. The technique is capable of recording the phase shift of hard X-rays travelling through a sample, which greatly enhances the contrast of low absorbing specimen compared to conventional amplitude contrast images. Unlike other existing X-ray phase contrast imaging methods, the grating interferometer also works with incoherent radiation from a standard X-ray tube. The key components are three gratings with silicon and gold structures, which have dimensions in the micrometer range and high aspect ratios. The fabrication processes, which involve photolithography, anisotropic wet etching, and electroplating, are described in this article for each of the three gratings. An example of an X-ray phase contrast image acquired with the grating interferometer is given. [Copyright &y& Elsevier]