A compact system for intraoperative specimen imaging based on edge illumination x-ray phase contrast.

A significant number of patients receiving breast-conserving surgery (BCS) for invasive carcinoma and ductal carcinoma in situ (DCIS) may need reoperation following tumor-positive margins from final histopathology tests. All current intraoperative margin assessment modalities have specific limitations. As a first step towards the development of a compact system for intraoperative specimen imaging based on edge illumination x-ray phase contrast, we prove that the system's dimensions can be reduced without affecting imaging performance. We analysed the variation in noise and contrast to noise ratio (CNR) with decreasing system length using the edge illumination x-ray phase contrast imaging setup. Two-(planar) and three-(computed tomography (CT)) dimensional imaging acquisitions of custom phantoms and a breast tissue specimen were made. Dedicated phase retrieval algorithms were used to separate refraction and absorption signals. A 'single-shot' retrieval method was also used, to retrieve thickness map images, due to its simple acquisition procedure and reduced acquisition times. Experimental results were compared to numerical simulations where appropriate. The relative contribution of dark noise signal in integrating detectors is significant for low photon count statistics acquisitions. Under constant exposure factors and magnification, a more compact system provides an increase in CNR. Superior CNR results were obtained for refraction and thickness map images when compared to absorption images. Results indicate that the 'single-shot' acquisition method is preferable for a compact CT intraoperative specimen scanner; it allows for shorter acquisition times and its combination of the absorption and refraction signals ultimately leads to a higher contrast. The first CT images of a breast specimen acquired with the compact system provided promising results when compared to those of the longer length system.

Retrieval of weak x-ray scattering using edge illumination.

X-ray phase contrast imaging provides additional modes of image contrast compared to conventional attenuation-based x-ray imaging, thus providing additional structural and functional information about the sample. The edge-illumination (EI) technique has been used to provide attenuation, refraction, and scattering contrast in both biological and non-biological samples. However, the retrieval of low scattering signals by fitting a single Gaussian remains problematic, principally due to the inability of the EI system to achieve perfect dark-field illumination. We present a new retrieval method that fits three Gaussians, which successfully overcomes this limitation, and provide examples of the retrieval of such signals in highly absorbing, weakly scattering samples.

Edge illumination X-ray phase tomography of multi-material samples using a single-image phase retrieval algorithm.

In this paper we present a single-image phase retrieval algorithm for multi-material samples, developed for the edge illumination (EI) X-ray phase contrast imaging method. The theoretical derivation is provided, along with any assumptions made. The algorithm is evaluated quantitatively using both simulated and experimental results from a computed tomography (CT) scan using the EI laboratory implementation. Qualitative CT results are provided for a biological sample containing both bone and soft-tissue. Using a single EI image per projection and knowledge of the complex refractive index, the algorithm can accurately retrieve the interface between a given pair of materials. A composite CT slice can be created by splicing together multiple CT reconstructions, each retrieved for a different pair of materials.

Large field of view, fast and low dose multimodal phase-contrast imaging at high x-ray energy.

X-ray phase contrast imaging (XPCI) is an innovative imaging technique which extends the contrast capabilities of 'conventional' absorption based x-ray systems. However, so far all XPCI implementations have suffered from one or more of the following limitations: low x-ray energies, small field of view (FOV) and long acquisition times. Those limitations relegated XPCI to a 'research-only' technique with an uncertain future in terms of large scale, high impact applications. We recently succeeded in designing, realizing and testing an XPCI system, which achieves significant steps toward simultaneously overcoming these limitations. Our system combines, for the first time, large FOV, high energy and fast scanning. Importantly, it is capable of providing high image quality at low x-ray doses, compatible with or even below those currently used in medical imaging. This extends the use of XPCI to areas which were unpractical or even inaccessible to previous XPCI solutions. We expect this will enable a long overdue translation into application fields such as security screening, industrial inspections and large FOV medical radiography - all with the inherent advantages of the XPCI multimodality.

A single-image retrieval method for edge illumination X-ray phase-contrast imaging: Application and noise analysis.

PURPOSE: Edge illumination (EI) X-ray phase-contrast imaging (XPCI) has been under development at University College London in recent years, and has shown great potential for both laboratory and synchrotron applications. In this work, we propose a new acquisition and processing scheme. Contrary to existing retrieval methods for EI, which require as input two images acquired in different setup configurations, the proposed approach can retrieve an approximate map of the X-ray phase from a single image, thus significantly simplifying the acquisition procedure and reducing data collection times. METHODS: The retrieval method is analytically derived, based on the assumption of a quasi-homogeneous object, i.e. an object featuring a constant ratio between refractive index and absorption coefficient. The noise properties of the input and retrieved images are also theoretically analyzed under the developed formalism. The method is applied to experimental synchrotron images of a biological object. RESULTS: The experimental results show that the method can provide high-quality images, where the "edge" signal typical of XPCI images is transformed to an "area" contrast that enables an easier interpretation of the sample geometry. Moreover, the retrieved images confirm that the method is highly stable against noise. CONCLUSIONS: We anticipate that the developed approach will become the method of choice for a variety of applications of EI XPCI, thanks to its ability to simplify the acquisition procedure and reduce acquisitions time and dose to the sample. Future work will focus on the adaptation of the method to computed tomography and to polychromatic radiation from X-ray tubes.

Robust phase retrieval for high resolution edge illumination x-ray phase-contrast computed tomography in non-ideal environments.

Edge illumination x-ray phase contrast tomography is a recently developed imaging technique which enables three-dimensional visualisation of low-absorbing materials. Dedicated phase retrieval algorithms can provide separate computed tomography (CT) maps of sample absorption, refraction and scattering properties. In this paper we propose a novel "modified local retrieval" method which is capable of accurately retrieving sample properties in a range of realistic, non-ideal imaging environments. These include system misalignment, defects in the used optical elements and system geometry variations over time due to vibrations or temperature fluctuations. System instabilities were analysed, modelled and incorporated into a simulation study. As a result, an additional modification was introduced to the retrieval procedure to account for changes in the imaging system over time, as well as local variations over the field of view. The performance of the proposed method was evaluated in comparison to a previously used "global retrieval" method by applying both approaches to experimental CT data of a rat's heart acquired in a non-ideal environment. The use of the proposed method resulted in the removal of major artefacts, leading to a significant improvement in image quality. This method will therefore enable acquiring high-resolution, reliable CT data of large samples in realistic settings.

Concept of contrast transfer function for edge illumination x-ray phase-contrast imaging and its comparison with the free-space propagation technique.

Previous studies on edge illumination (EI) X-ray phase-contrast imaging (XPCi) have investigated the nature and amplitude of the signal provided by this technique. However, the response of the imaging system to different object spatial frequencies was never explicitly considered and studied. This is required in order to predict the performance of a given EI setup for different classes of objects. To this scope, in the present work we derive analytical expressions for the contrast transfer function of an EI imaging system, using the approximation of near-field regime, and study its dependence upon the main experimental parameters. We then exploit these results to compare the frequency response of an EI system with respect of that of a free-space propagation XPCi one. The results achieved in this work can be useful for predicting the signals obtainable for different types of objects and also as a basis for new retrieval methods.

Asymmetric masks for laboratory-based X-ray phase-contrast imaging with edge illumination.

We report on an asymmetric mask concept that enables X-ray phase-contrast imaging without requiring any movement in the system during data acquisition. The method is compatible with laboratory equipment, namely a commercial detector and a rotating anode tube. The only motion required is that of the object under investigation which is scanned through the imaging system. Two proof-of-principle optical elements were designed, fabricated and experimentally tested. Quantitative measurements on samples of known shape and composition were compared to theory with good agreement. The method is capable of measuring the attenuation, refraction and (ultra-small-angle) X-ray scattering, does not have coherence requirements and naturally adapts to all those situations in which the X-ray image is obtained by scanning a sample through the imaging system.

X-ray absorption, phase and dark-field tomography through a beam tracking approach.

We present a development of the beam-tracking approach that allows its implementation in computed tomography. One absorbing mask placed before the sample and a high resolution detector are used to track variations in the beam intensity distribution caused by the sample. Absorption, refraction, and dark-field are retrieved through a multi-Gaussian interpolation of the beam. Standard filtered back projection is used to reconstruct three dimensional maps of the real and imaginary part of the refractive index, and of the dark-field signal. While the method is here demonstrated using synchrotron radiation, its low coherence requirements suggest a possible implementation with laboratory sources.

Single-image phase retrieval using an edge illumination X-ray phase-contrast imaging setup.

A method is proposed which enables the retrieval of the thickness or of the projected electron density of a sample from a single input image acquired with an edge illumination phase-contrast imaging setup. The method assumes the case of a quasi-homogeneous sample, i.e. a sample with a constant ratio between the real and imaginary parts of its complex refractive index. Compared with current methods based on combining two edge illumination images acquired in different configurations of the setup, this new approach presents advantages in terms of simplicity of acquisition procedure and shorter data collection time, which are very important especially for applications such as computed tomography and dynamical imaging. Furthermore, the fact that phase information is directly extracted, instead of its derivative, can enable a simpler image interpretation and be beneficial for subsequent processing such as segmentation. The method is first theoretically derived and its conditions of applicability defined. Quantitative accuracy in the case of homogeneous objects as well as enhanced image quality for the imaging of complex biological samples are demonstrated through experiments at two synchrotron radiation facilities. The large range of applicability, the robustness against noise and the need for only one input image suggest a high potential for investigations in various research subjects.

Achromatic approach to phase-based multi-modal imaging with conventional X-ray sources.

Compatibility with polychromatic radiation is an important requirement for an imaging system using conventional rotating anode X-ray sources. With a commercially available energy-resolving single-photon-counting detector we investigated how broadband radiation affects the performance of a multi-modal edge-illumination phase-contrast imaging system. The effect of X-ray energy on phase retrieval is presented, and the achromaticity of the method is experimentally demonstrated. Comparison with simulated measurements integrating over the energy spectrum shows that there is no significant loss of image quality due to the use of polychromatic radiation. This means that, to a good approximation, the imaging system exploits radiation in the same way at all energies typically used in hard-X-ray imaging.

Inclusion of coherence in Monte Carlo models for simulation of x-ray phase contrast imaging.

Interest in phase contrast imaging methods based on electromagnetic wave coherence has increased significantly recently, particularly at X-ray energies. This is giving rise to a demand for effective simulation methods. Coherent imaging approaches are usually based on wave optics, which require significant computational resources, particularly for producing 2D images. Monte Carlo (MC) methods, used to track individual particles/photons for particle physics, are not considered appropriate for describing coherence effects. Previous preliminary work has evaluated the possibility of incorporating coherence in Monte Carlo codes. However, in this paper, we present the implementation of refraction in a model that is based on time of flight calculations and the Huygens-Fresnel principle, which allow reproducing the formation of phase contrast images in partially and fully coherent experimental conditions. The model is implemented in the FLUKA Monte Carlo code and X-ray phase contrast imaging simulations are compared with experiments and wave optics calculations.

Phase retrieval through a one-dimensional ptychographic engine.

Ptychographic techniques are currently the subject of increasing scientific interest due to their capability to retrieve the complex transmission function of an object at very high resolution. However, they impose a substantial burden in terms of acquisition time and dimension of the scanned area, which limits the range of samples that can be studied. We have developed a new method that combines the ptychographic approach in one direction with Fresnel propagation in the other by employing a strongly asymmetric probe. This enables scanning the sample in one direction only, substantially reducing exposure times while covering a large field of view. This approach sacrifices ptychographic-related resolution in one direction, but removes any limitation on the probe dimension in the direction orthogonal to the scanning, enabling the scan of relatively large objects without compromising exposure times.

Spatial resolution of edge illumination X-ray phase-contrast imaging.

We analyze the spatial resolution of edge illumination X-ray phase-contrast imaging and its dependence upon various experimental parameters such as source size, source-to-sample and sample-to-detector distances, X-ray energy and size of the beam-shaping aperture. Different propagation regimes, as well as the beam divergence and polychromaticity encountered with laboratory sources, are also considered. We show that spatial resolution in edge illumination phase-contrast imaging presents peculiar features compared to other X-ray phase-contrast techniques. In particular, in the direction orthogonal to the s or mask lines used to shape the beam, this can be better than both the pixel dimension and the projected source size. Numerical simulations based on Fresnel diffraction integrals are presented, which confirm the analytical predictions. The obtained results allow a simple estimation of the spatial resolution for edge-illumination phase imaging in both synchrotron and laboratory setups.

Phase-contrast microscopy at high x-ray energy with a laboratory setup.

We report on the design and realization of an x-ray imaging system for quantitative phase-contrast microscopy at high x-ray energy with laboratory-scale instrumentation. Phase and amplitude were separated quantitatively at x-ray energies up to 80 keV with micrometric spatial resolution. The accuracy of the results was tested against numerical simulations, and the spatial resolution was experimentally quantified by measuring a Siemens star phase object. This simple setup should find broad application in those areas of x-ray imaging where high energy and spatial resolution are simultaneously required and in those difficult cases where the sample contains materials with similar x-ray absorption.

Strategies for efficient and fast wave optics simulation of coded-aperture and other x-ray phase-contrast imaging methods.

We derive a Fourier formulation of coded-aperture x-ray phase-contrast imaging, based on the wave theory of optics in the Fresnel approximation. We use this model to develop a flexible, efficient, and general simulation algorithm that can be easily adapted to other implementations of x-ray phase contrast imaging. Likewise, the algorithm enables a simple extension to 2D aperture designs, different acquisition schemes, etc. Problems related to numerical implementation of the algorithm are analyzed in detail, and simple rules are derived that enable us to avoid or at least mitigate them. Finally, comparisons with experimental data and data obtained with a different simulation algorithm are presented to validate the model and demonstrate its advantages in practical implementations. This also enabled us to demonstrate an increase in computational speed of more than one order of magnitude over a previous algorithm.