Search

Here we report a method for increased resolution of single exposure three modality x-ray images using super-resolution. The three x-ray image modalities are absorption-, differential phase-contrast-, and dark-field-images. To create super-resolution, a non-mechanically movable micro-focus x-ray source is used. A series of almost identical x-ray projection images is obtained while the point source is translated in a two-dimensional grid pattern. The three image modalities are extracted from fourier space using spatial harmonic analysis, also known as the single-shot method. Using super-resolution on the low-resolution series of the three modalities separately results in high-resolution images for the modalities. This approach allows to compensate for the inherent loss in resolution caused by the single-shot method without increasing the need for stability or algorithms accounting for possible motion.

Purpose: To explore the potential of grating-based x-ray phase-contrast imaging for clinical applications, a first compact gantry system was developed. It is designed such that it can be implemented into anin-vivo small-animal phase-contrast computed tomography (PC-CT) scanner. The purpose of the present study is to assess the accuracy and quantitativeness of the described gantry in both absorption and phase-contrast. Methods: A phantom, containing six chemically well-defined liquids, was constructed. A tomography scan with cone-beam reconstruction of this phantom was performed yielding the spatial distribution of the linear attenuation coefficient μ and decrement δ of the complex refractive index. Theoretical values of μ and δ were calculated for each liquid from tabulated data and compared with the experimentally measured values. Additionally, a color-fused image representation is proposed to display the complementary absorption and phase-contrast information in a single image. Results: Experimental and calculated data of the phantom agree well confirming the quantitativeness and accuracy of the reconstructed spatial distributions of μ and δ. The proposed color-fused image representation, which combines the complementary absorption and phase information, considerably helps in distinguishing the individual substances. Conclusions: The concept of grating-based phase-contrast computed tomography(CT) can be implemented into a compact, cone-beam geometry gantry setup. The authors believe that this work represents an important milestone in translating phase-contrast x-ray imaging from previous proof-of-principle experiments to first preclinical biomedical imaging applications on small-animal models.

Here we review our recent progress in the field of X-ray dark-field and phase-contrast imaging using a grating interferometer. We describe the basic imaging principles of grating-based phase-contrast and dark-field radiography and present some exemplary results obtained for simple test objects and biological specimens. Furthermore, we discuss how phase-contrast and dark-field radiography can be combined with the concept of computed tomography, and yield highly detailed three-dimensional insights into biomedical sample. Exemplary results obtained with standard X-ray tube sources and highly brilliant synchrotron sources are presented.

The first imaging results obtained from a small-size synchrotron are reported. The newly developed Compact Light Source produces inverse Compton X-rays at the intersection point of the counter propagating laser and electron beam. The small size of the intersection point gives a highly coherent cone beam with a few milliradian angular divergence and a few percent energy spread. These specifications make the Compact Light Source ideal for a recently developed grating-based differential phase-contrast imaging method.

Between X-ray tubes and large-scale synchrotron sources, a large gap in performance exists with respect to the monochromaticity and brilliance of the X-ray beam. However, due to their size and cost, large-scale synchrotrons are not available for more routine applications in small and medium-sized academic or industrial laboratories. This gap could be closed by laser-driven compact synchrotron light sources (CLS), which use an infrared (IR) laser cavity in combination with a small electron storage ring. Hard X-rays are produced through the process of inverse Compton scattering upon the intersection of the electron bunch with the focused laser beam. The produced X-ray beam is intrinsically monochromatic and highly collimated. This makes a CLS well-suited for applications of more advanced--and more challenging--X-ray imaging approaches, such as X-ray multimodal tomography. Here we present, to our knowledge, the first results of a first successful demonstration experiment in which a monochromatic X-ray beam from a CLS was used for multimodal, i.e., phase-, dark-field, and attenuation-contrast, X-ray tomography. We show results from a fluid phantom with different liquids and a biomedical application example in the form of a multimodal CT scan of a small animal (mouse, ex vivo). The results highlight particularly that quantitative multimodal CT has become feasible with laser-driven CLS, and that the results outperform more conventional approaches.

X-ray phase-contrast imaging has recently led to a revolution in resolving power and tissue contrast in biomedical imaging, microscopy and materials science. The necessary high spatial coherence is currently provided by either large-scale synchrotron facilities with limited beamtime access or by microfocus X-ray tubes with rather limited flux. X-rays radiated by relativistic electrons driven by well-controlled high-power lasers offer a promising route to a proliferation of this powerful imaging technology. A laser-driven plasma wave accelerates and wiggles electrons, giving rise to brilliant keV X-ray emission. This so-called Betatron radiation is emitted in a collimated beam with excellent spatial coherence and remarkable spectral stability. Here we present the first phase-contrast micro-tomogram revealing quantitative electron density values of a biological sample using betatron X-rays, and a comprehensive source characterization. Our results suggest that laser-based X-ray technology offers the potential for filling the large performance gap between synchrotron- and current X-ray tube-based sources., 16 pages, 5 figures, submitted to Nature Communication

The main shortcoming of conventional biomedical x-ray imaging is the weak soft-tissue contrast caused by the small differences in the absorption coefficients between different materials. This issue can be addressed by x-ray phasesensitive imaging approaches, e.g. x-ray Talbot-Lau grating interferometry. The advantage of the three-grating Talbot-Lau approach is that it allows to acquire x-ray phase-contrast and dark-field images with a conventional lab source. However, through the introduction of the grating interferometer some constraints are imposed on the setup geometry. In general, the grating pitch and the mean x-ray energy determine the setup dimensions. The minimal length of the setup increases linearly with energy and is proportional to p2, where p is the grating pitch. Thus, a high-energy (100 keV) compact grating-based setup for x-ray imaging can be realized only if gratings with aspect-ratio of approximately 300 and a pitch of 1-2 μm were available. However, production challenges limit the availability of such gratings. In this study we consider the use of non-binary phase-gratings as means of designing a more compact grating interferometer for phase-contrast imaging. We present simulation and experimental data for both monochromatic and polychromatic case. The results reveal that phase-gratings with triangular-shaped structures yield visibilities that can be used for imaging purposes at significantly shorter distances than binary gratings. This opens the possibility to design a high-energy compact setup for x-ray phase-contrast imaging. Furthermore, we discuss different techniques to achieve triangular-shaped phase-shifting structures.

X-ray imaging using a Talbot-Lau interferometer, consisting of three binary gratings, is a well-established approach to acquire x-ray phase-contrast and dark-field images with a polychromatic source. However, challenges in the production of high aspect ratio gratings limit the construction of a compact setup for high x-ray energies. In this study we consider the use of phase gratings with triangular-shaped structures in an x-ray interferometer and show that such gratings can yield high visibilities for significantly shorter propagation distances than conventional gratings with binary structures. The findings are supported by simulation and experimental results for both cases of a monochromatic and a polychromatic source.

While the performance of conventional x-ray tube sources often suffers from the broad polychromatic spectrum, synchrotrons that could provide highly brilliant x-rays are restricted to large research facilities and impose high investment and maintenance costs. Lately, a new type of compact synchrotron sources has been investigated. These compact light sources (CLS) based on inverse Compton scattering provide quasi-monochromatic hard x-rays. The flux and brilliance yielded by a CLS currently lie between x-ray tube sources and third-generation synchrotrons. The relatively large partially coherent x-ray beam is well suited for the investigation of preclinical applications of grating-based phase-contrast and dark-field imaging. Here we present the first grating-based multimodal tomosynthesis images of a human breast slice acquired at a CLS to investigate the possibilities of improved breast cancer diagnostics.

We report on the first experimental results of helical differential phase-contrast computed tomography (helical DPC-CT) with a laboratory X-ray tube source and a Talbot-Lau grating interferometer. The results experimentally verify the feasibility of helical data acquisition and reconstruction in phase-contrast imaging, in analogy to its use in clinical CT systems. This allows fast and continuous volumetric scans for long objects with lengths exceeding the dimension of the detector. Since helical CT revolutionized the field of medical CT several years ago, we anticipate that this method will bring the same significant impact on the future medical and industrial applications of X-ray DPC-CT.

Pulmonary emphysema is a widespread disorder characterized by irreversible destruction of alveolar walls. The spatial distribution of the disease, so far, could only be obtained using an X-ray CT scan, implying a high patient dose. X-ray scattering on alveolar structures is measured in the dark-field signal. The signal is dependent on the size of alveoli and therefore, a combination of absorption and darkfield signal is explored for mapping the distribution of emphysema in the lung on x-ray projection images. In this study three excised murine lungs with pulmonary emphysema and three control samples were imaged using a compact, cone-beam, small-animal x-ray dark-field scanner with a polychromatic source. Statistical analysis of the results, based on a combination of transmission and darkfield signals, revealed a distinct difference between emphysematous and control samples. Subsequently, the distribution of emphysema was mapped out per-pixel for the lungs and showed good agreement with histological findings.

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

International audience; Invasive cancer causes a change in density in the affected tissue, which can be visualized by x-ray phase-contrast tomography. However, the diagnostic value of this method has so far not been investigated in detail. Therefore, the purpose of this study was, in a blinded manner, to investigate whether malignancy could be revealed by non-invasive x-ray phase-contrast tomography in lymph nodes from breast cancer patients. Seventeen formalin-fixed paraffin-embedded lymph nodes from 10 female patients (age range 37–83 years) diagnosed with invasive ductal carcinomas were analyzed by X-ray phase-contrast tomography. Ten lymph nodes had metastatic deposits and 7 were benign. The phase-contrast images were analyzed according to standards for conventional CT images looking for characteristics usually only visible by pathological examinations. Histopathology was used as reference. The result of this study was that the diagnostic sensitivity of the image analysis for detecting malignancy was 100% and the specificity was 87%. The positive predictive value was 91% for detecting malignancy and the negative predictive value was 100%. We conclude that x-ray phase-contrast imaging can accurately detect density variations to obtain information regarding lymph node involvement previously inaccessible with standard absorption x-ray imaging.

International audience; To explore the potential of grating-based x-ray phase-contrast computed tomography (CT) for preclinical research, a genetically engineered mouse model of pancreatic ductal adenocarcinoma (PDAC) was investigated. One ex-vivo mouse specimen was scanned with different grating-based phase-contrast CT imaging setups covering two different settings: i) high-resolution synchrotron radiation (SR) imaging and ii) dose-reduced imaging using either synchrotron radiation or a conventional x-ray tube source. These experimental settings were chosen to assess the potential of phase-contrast imaging for two different types of application: i) high-performance imaging for virtual microscopy applications and ii) biomedical imaging with increased soft-tissue contrast for in-vivo applications. For validation and as a reference, histological slicing and magnetic resonance imaging (MRI) were performed on the same mouse specimen. For each x-ray imaging setup, attenuation and phase-contrast images were compared visually with regard to contrast in general, and specifically concerning the recognizability of lesions and cancerous tissue. To quantitatively assess contrast, the contrast-to-noise ratios (CNR) of selected regions of interest (ROI) in the attenuation images and the phase images were analyzed and compared. It was found that both for virtual microscopy and for in-vivo applications, there is great potential for phase-contrast imaging: in the SR-based benchmarking data, fine details about tissue composition are accessible in the phase images and the visibility of solid tumor tissue under dose-reduced conditions is markedly superior in the phase images. The present study hence demonstrates improved diagnostic value with phase-contrast CT in a mouse model of a complex endogenous cancer, promoting the use and further development of grating-based phase-contrast CT for biomedical imaging applications

We have developed a compact grating-based in-vivo phase-contrast micro-CT system with a rotating gantry. The 50 W microfocus x-ray source operates with 20 to 50 kV peak energy. The length of the rotating interferometer is around 47 cm. Pixel size in the object is 30 micron; the field of view is approx. 35 mm in diameter, suited to image a mouse. The interferometer consists of three gratings: an absorption grating close to the x-ray source, a phase grating to introduce a π/2 phase shift and an absorption analyzer grating positioned at the first fractional Talbot distance. Numerous drives and actuators are used to provide angular and linear grating alignment, phase stepping and object/gantry precision positioning. Phantom studies were conducted to investigate performance, accuracy and stability of the scanner. In particular, the influences of gantry rotation and of temperature fluctuations on the interferometric image acquisition were characterized. Also dose measurements were performed. The first imaging results obtained with the system show the complementary nature of phase-contrast micro-CT images with respect to absorption-based micro-CT. Future improvements, necessary to optimize the scanner for in-vivo small-animal CT scanning on a regular and easy-to-use basis, are also discussed.

To explore the future clinical potential of improved soft-tissue visibility with grating-based X-ray phase contrast (PC), we have developed a first preclinical computed tomography (CT) scanner featuring a rotating gantry. The main challenge in the transition from previous bench-top systems to a preclinical scanner are phase artifacts that are caused by minimal changes in the grating alignment during gantry rotation. In this paper, we present the first experimental results from the system together with an adaptive phase recovery method that corrects for these phase artifacts. Using this method, we show that the scanner can recover quantitatively accurate Hounsfield units in attenuation and phase. Moreover, we present a first tomography scan of biological tissue with complementary information in attenuation and phase contrast. The present study hence demonstrates the feasibility of grating-based phase contrast with a rotating gantry for the first time and paves the way for future in vivo studies on small animal disease models (in the mid-term future) and human diagnostics applications (in the long-term future).

Dark-field images are formed from x-ray small-angle scattering signals. The small-angle scattering signals are particularly sensitive to structural variation and density fluctuation on a length scale of several tens to hundreds of nanometers, offering a unique contrast mechanism to reveal subtle structural features of an object. In this study, based on the principle of energy conservation, we develop a physical model to describe the relationship between x-ray small-angle scattering coefficients of an object and dark-field intensity images. This model can be used to reconstruct volumetric x-ray small-angle scattering images of an object using classical tomographic algorithms. We also establish a relationship between the small-angle scattering intensity and the visibility function measured with x-ray grating imaging. The numerical simulations and phantom experiments have demonstrated the accuracy and practicability of the proposed model.

The Compact Light Source is a miniature synchrotron producing X-rays at the interaction point of a counter-propagating laser pulse and electron bunch through the process of inverse Compton scattering. The small transverse size of the luminous region yields a highly coherent beam with an angular divergence of a few milliradians. The intrinsic monochromaticity and coherence of the produced X-rays can be exploited in high-sensitivity differential phase-contrast imaging with a grating-based interferometer. Here, the first multimodal X-ray imaging experiments at the Compact Light Source at a clinically compatible X-ray energy of 21 keV are reported. Dose-compatible measurements of a mammography phantom clearly demonstrate an increase in contrast attainable through differential phase and dark-field imaging over conventional attenuation-based projections.

X-ray phase and dark-field contrast have recently been the source of much attention in the field of X-ray imaging, as they both contribute new imaging signals based on physical principles that differ from conventional X-ray imaging. With a so-called Talbot grating interferometer, both phase-contrast and dark-field images are obtained simultaneously with the conventional attenuation-based X-ray image, providing three complementary image modalities that are intrinsically registered. Whereas the physical contrast mechanisms behind attenuation and phase contrast are well understood, a formalism to describe the dark-field signal is still in progress. In this article, we report on correlative experimental results obtained with a grating interferometer and with small-angle X-ray scattering. Furthermore, we use a proposed model to quantitatively describe the results, which could be of great importance for future clinical and biomedical applications of grating-based X-ray imaging.

Recently a novel grating based x-ray imaging approach called directional x-ray dark-field imaging was introduced. Directional x-ray dark-field imaging yields information about the local texture of structures smaller than the pixel size of the imaging system. In this work we extend the theoretical description and data processing schemes for directional dark-field imaging to strongly scattering systems, which could not be described previously. We develop a simple scattering model to account for these recent observations and subsequently demonstrate the model using experimental data. The experimental data includes directional dark-field images of polypropylene fibers and a human tooth slice.

In this paper we describe the design of different X-ray Talbot interferometers that have been built at the tomography beamline ID19 of the European Synchrotron Radiation Facility (ESRF) in Grenoble, France, and give a short review of performance characteristics, of current developments, and of the results obtained with these instruments so far. Among the applications so far, soft-tissue imaging has been a particular focus, as demonstrated in a recent paper by Schulz et al. (J. Roy. Soc. Interface, in press).

The basic principles of x-ray image formation in radiography have remained essentially unchanged since R¨ontgen 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. 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 Linear Diffusion Coefficient, 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.

New developments in X-ray instrumentation and analysis have facilitated the development and improvement of various scanning X-ray microscopy techniques. In this contribution, we offer an overview of recent scanning hard X-ray microscopy measurements performed at the Swiss Light Source. We discuss scanning transmission X-ray microscopy in its transmission, phase contrast, and dark-field imaging modalities. We demonstrate how small-angle X-ray scattering analysis techniques can be used to yield additional information. If the illumination is coherent, coherent diffraction imaging techniques can be brought to bear. We discuss how, from scanning microscopy measurements, detailed measurements of the X-ray scattering distributions can be used to extract high-resolution images. These microscopy techniques with their respective imaging power can easily be combined to multimodal X-ray microscopy.

Here we present our recent progress in the field of x-ray dark-field and phase-contrast imaging using a grating interferometer. We describe the basic imaging principles of grating-based phase-contrast and dark-field radiography and present some exemplary results obtained for simple test objects and biological specimens. Exemplary results obtained with standard x-ray tube sources.

We report advances and complementary results concerning a recently developed method for high-sensitivity grating-based hard x-ray phase tomography. We demonstrate how the soft tissue sensitivity of the technique can be used to obtain in-vitro tomographic images of a tumor bearing rat brain specimen, without use of contrast agents. In particular, we demonstrate that brain tumors and the white and gray brain matter structure in a rat's cerebellum can be resolved by this approach. The findings are potentially interesting from a clinical point of view, since a similar approach using three transmission gratings can be implemented with more readily available x-ray sources, such as standard x-ray tubes. Moreover, open the results the way to in-vivo experiments in the near future.

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.

We report on an x-ray cone-beam differential phase-contrast computed laminography (DPC-CL) method for tomographic reconstruction of thin and lamellar objects. We describe the specific scan geometry of DPC-CL, which consists of a Talbot-Lau grating interferometer and a lab-based x-ray tube source, and derive a filtered back-projection (FBP) reconstruction algorithm. The experimental results of a flat sphere phantom and a piece of ham demonstrate the validity of the proposed technique. The existing DPC-CL methods are based on synchrotron sources and the parallel-beam geometry. In contrast, our approach adopts a more accessible x-ray tube source and a cone-beam geometry. Therefore it significantly widens the application range of phase-contrast laminography, particularly in practical laboratory settings, beyond applications at large-scale synchrotron facilities.

We report on an interlaced acquisition scheme in grating-based x-ray phase-contrast tomography in which different viewing angles are used to retrieve a single differential phase projection. This interlaced acquisition scheme is particularly beneficial for region-of-interest tomography since it substantially reduces the artifacts caused by the external region and can eliminate the need for stop-and-go motion of the tomography rotation axis. In this letter, the higher accuracy of the region-of-interest phase reconstructions obtained with the interlaced approach is demonstrated by numerical simulation and experimental results.

We describe a small-angle x-ray scattering-based imaging technique that reveals the distribution and orientation of nano-scale structures over extended areas. By combining two measurement and analysis schemes, complementary structural information is available which renders the technique suitable for a broad range of applications, e. g. in materials science and bio-imaging. Through a combination of current techniques and on-line analysis schemes, measurements with a so far unprecedented combination of speed, dynamic range and point density became feasible. This is illustrated by data recorded for a section of a mouse soleus muscle visualizing fine muscle and Achilles tendon structures down to the 10 nm range over a 10 mm(2) sample area.

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.

We report numerical and experimental results demonstrating accurate region-of-interest computed tomography (CT) reconstruction based on differential phase-contrast projection (DPC) images. The approach removes the constraint of covering the entire sample within the field of view of the image detector. Particularly for biomedical applications, the presented DPC-CT region-of-interest approach will allow for the visualization of previously inaccessible details deep inside an entire animal or organ. We envisage that this development will also be of interest for potential future clinical applications, because grating-based DPC-CT can be implemented with standard x-ray tube sources.

Laser-wakefield-accelerated electrons were used to drive an all-optical undulator source, a 5-keV betatron X-ray source and a tunable quasi-monochromatic Compton-X-ray source. Also, we present a phase-contrast tomogram of a fly obtained with the betatron beam. © 2014 OSA.