Utility of knife-edge position tracking in cycloidal computed tomography.

Cycloidal computed tomography provides high-resolution images within relatively short scan times by combining beam modulation with dedicated under-sampling. However, implementing the technique relies on accurate knowledge of the sample's motion, particularly in the case of continuous scans, which is often unavailable due to hardware or software limitations. We have developed an easy-to-implement position tracking technique using a sharp edge, which can provide reliable information about the trajectory of the sample and thus improve the reconstruction process. Furthermore, this approach also enables the development of other innovative sampling schemes, which may otherwise be difficult to implement.

Endoscopic eradication therapy for Barrett's esophagus-related neoplasia: a final 10-year report from the UK National HALO Radiofrequency Ablation Registry.

BACKGROUND AND AIMS: Long-term durability data for effectiveness of radiofrequency ablation (RFA) to prevent esophageal adenocarcinoma in patients with dysplastic Barrett's esophagus (BE) are lacking. METHODS: We prospectively collected data from 2535 patients with BE (mean length, 5.2 cm; range, 1-20) and neoplasia (20% low-grade dysplasia, 54% high-grade dysplasia, 26% intramucosal carcinoma) who underwent RFA therapy across 28 UK hospitals. We assessed rates of invasive cancer and performed detailed analyses of 1175 patients to assess clearance rates of dysplasia (CR-D) and intestinal metaplasia (CR-IM) within 2 years of starting RFA therapy. We assessed relapses and rates of return to CR-D (CR-D2) and CR-IM (CR-IM2) after further therapy. CR-D and CR-IM were confirmed by an absence of dysplasia and intestinal metaplasia on biopsy samples taken at 2 consecutive endoscopies. RESULTS: Ten years after starting treatment, the Kaplan-Meier (KM) cancer rate was 4.1% with a crude incidence rate of .52 per 100 patient-years. CR-D and CR-IM after 2 years of therapy were 88% and 62.6%, respectively. KM relapse rates were 5.9% from CR-D and 18.7% from CR-IM at 8 years, with most occurring in the first 2 years. Both were successfully retreated with rates of CR-D2 of 63.4% and CR-IM2 of 70.0% 2 years after retreatment. EMR before RFA increased the likelihood of rescue EMR from 17.2% to 41.7% but did not affect the rate of CR-D, whereas rescue EMR after RFA commenced reduced CR-D from 91.4% to 79.7% (χ2P < .001). CONCLUSIONS: RFA treatment is effective and durable to prevent esophageal adenocarcinoma. Most treatment relapses occur early and can be successfully retreated.

Freestanding high-aspect-ratio gold masks for low-energy, phase-based x-ray microscopy.

High-resolution, x-ray phase contrast microscopy, a key technique with promising potential in biomedical imaging and diagnostics, is based on narrow-slit high-aspect-ratio gold gratings. We present the development, fabrication details, and experimental testing of the freestanding 10µm thick gold membrane masks with an array of 0.9-1.5µm void slit apertures for a novel low-energy x-ray microscope. The overall mask size is 4 mm × 4 mm, with a grating pitch of 7.5µm, 6.0-6.6µm wide gold bars are supported by 3µm wide crosslinks at 400µm intervals. The fabrication process is based on gold electroplating into a silicon mold coated with various thin films to form a voltage barrier, plating base, and sacrificial layer, followed by the mold removal to obtain the freestanding gold membrane with void slit apertures. We discuss key aspects for the materials and processes, including gold structures homogeneity, residual stresses, and prevention of collapsing of the grid elements. We further demonstrate the possibility to obtain high-resolution, high contrast 2D images of biological samples using an incoherent, rotating anode x-ray tube.

Dynamic Multicontrast X-Ray Imaging Method Applied to Additive Manufacturing.

We present a dynamic implementation of the beam-tracking x-ray imaging method providing absorption, phase, and ultrasmall angle scattering signals with microscopic resolution and high frame rate. We demonstrate the method's ability to capture dynamic processes with 22-ms time resolution by investigating the melting of metals in laser additive manufacturing, which has so far been limited to single-modality synchrotron radiography. The simultaneous availability of three contrast channels enables earlier segmentation of droplets, tracking of powder dynamic, and estimation of unfused powder amounts, demonstrating that the method can provide additional information on melting processes.

Accuracy of clinical staging for T2N0 oesophageal cancer: systematic review and meta-analysis.

Oesophageal cancer is the sixth commonest cause of overall cancer mortality. Clinical staging utilizes multiple imaging modalities to guide treatment and prognostication. T2N0 oesophageal cancer is a treatment threshold for neoadjuvant therapy. Data on accuracy of current clinical staging tests for this disease subgroup are conflicting. We performed a meta-analysis of all primary studies comparing clinical staging accuracy using multiple imaging modalities (index test) to histopathological staging following oesophagectomy (reference standard) in T2N0 oesophageal cancer. Patients that underwent neoadjuvant therapy were excluded. Electronic databases (MEDLINE, Embase, Cochrane Library) were searched up to September 2019. The primary outcome was diagnostic accuracy of combined T&N clinical staging. Publication date, first recruitment date, number of centers, sample size and geographical location main histological subtype were evaluated as potential sources of heterogeneity. The search strategy identified 1,199 studies. Twenty studies containing 5,213 patients met the inclusion criteria. Combined T&N staging accuracy was 19% (95% CI, 15-24); T staging accuracy was 29% (95% CI, 24-35); percentage of patients with T downstaging was 41% (95% CI, 33-50); percentage of patients with T upstaging was 28% (95% CI, 24-32) and percentage of patients with N upstaging was 34% (95% CI, 30-39). Significant sources of heterogeneity included the number of centers, sample size and study region. T2N0 oesophageal cancer staging remains inaccurate. A significant proportion of patients were downstaged (could have received endotherapy) or upstaged (should have received neoadjuvant chemotherapy). These findings were largely unchanged over the past two decades highlighting an urgent need for more accurate staging tests for this subgroup of patients.

A comparative histological study of the osteoderms in the lizards Heloderma suspectum (Squamata: Helodermatidae) and Varanus komodoensis (Squamata: Varanidae).

We describe the histological appearance of the osteoderms (ODs) of Heloderma suspectum and Varanus komodoensis using multiple staining and microscopy techniques to yield information about their morphology and development. Histological analysis showed that the ODs of H. suspectum are composed of three main tissue types, a superficial layer, herein identified as osteodermine, capping a base composed of Sharpey-fibre bone and lamellar bone rich in secondary osteons (Haversian bone tissue). In contrast, ODs in V. komodoensis are composed of a core of woven bone surrounded by parallel-fibred bone without a capping tissue. Thus, in these two species, ODs differ both in terms of their structural composition and in details of their skeletogenesis. The histology of the mineralised tissues observed in these two reptile taxa provides insights into the mechanism of formation of lizard ODs and presents a direct comparison of the histological properties between the ODs of the two species. These data allow greater understanding of the comparative histological appearance of the dermal bones of lizards and highlight their structural diversity.

Simplified retrieval method for Edge Illumination X-ray phase contrast imaging allowing multi-modal imaging with fewer input frames.

We present data from an implementation of Edge Illumination (EI) that uses a detector aperture designed for increasing dynamic range, suitable for clinically relevant X-ray energies and demonstrated here using synchrotron radiation. By utilising a sufficiently large crosstalk between pixels, this implementation enables single-scan imaging for phase and absorption, and double-scan for phase, absorption and dark field imaging. The presence of the detector mask enables a direct comparison between conventional EI and beam tracking (BT), which we conduct through Monte Carlo and analytical modelling in the case of a single-scan being used for the retrieval of all three contrasts. In the present case, where the X-ray beam width is comparable to the pixel size, we provide an analysis on best-positioning of the beam on the detector for accurate signal retrieval. Further, we demonstrate an application of this method by distinguishing different concentrations of microbubbles via their dark field signals at high energy using an EI system.

Fast, non-iterative algorithm for quantitative integration of X-ray differential phase-contrast images.

X-ray phase contrast imaging is gaining importance as an imaging tool. However, it is common for X-ray phase detection techniques to be sensitive to the derivatives of the phase. Therefore, the integration of differential phase images is a fundamental step both to access quantitative pixel content and for further analysis such as segmentation. The integration of noisy data leads to artefacts with a severe impact on image quality and on its quantitative content. In this work, an integration method based on the Wiener filter is presented and tested using simulated and real data obtained with the edge illumination differential X-ray phase imaging method. The method is shown to provide high image quality while preserving the quantitative pixel content of the integrated image. In addition, it requires a short computational time making it suitable for large datasets.

Comparison of data-acquisition designs for single-shot edge-illumination X-ray phase-contrast tomography.

Edge-illumination X-ray phase-contrast tomography (EIXPCT) is an emerging technique that enables practical phase-contrast imaging with laboratory-based X-ray sources. A joint reconstruction method was proposed for reconstructing EIXPCT images, enabling novel flexible data-acquisition designs. However, only limited efforts have been devoted to optimizing data-acquisition designs for use with the joint reconstruction method. In this study, several promising designs are introduced, such as the constant aperture position (CAP) strategy and the alternating aperture position (AAP) strategy covering different angular ranges. In computer-simulation studies, these designs are analyzed and compared. Experimental data are employed to test the designs in real-world applications. All candidate designs are also compared for their implementation complexity. The tradeoff between data-acquisition time and image quality is discussed.

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.

Single-shot edge illumination x-ray phase-contrast tomography enabled by joint image reconstruction.

Edge illumination x-ray phase-contrast tomography (EIXPCT) is an emerging x-ray phase-contrast tomography technique for reconstructing the complex-valued x-ray refractive index distribution of an object. Conventional image reconstruction approaches for EIXPCT require multiple images to be acquired at each tomographic view angle. This contributes to prolonged data-acquisition times and elevated radiation doses, which can hinder in vivo applications. In this work, a new "single-shot" method is proposed for joint reconstruction (JR) of the real and imaginary-valued components of the refractive index distribution from a tomographic data set that contains only a single image acquired at each view angle. The proposed method is predicated on a nonlinear formulation of the inverse problem that is solved by using a gradient-based optimization method. The method is validated and investigated using computer-simulated and experimental EIXPCT data sets.

Interpretation and Utility of the Moments of Small-Angle X-Ray Scattering Distributions.

Small angle x-ray scattering has been proven to be a valuable method for accessing structural information below the spatial resolution limit implied by direct imaging. Here, we theoretically derive the relation that links the subpixel differential phase signal provided by the sample to the moments of scattering distributions accessible by refraction sensitive x-ray imaging techniques. As an important special case we explain the scatter or dark-field contrast in terms of the sample's phase signal. Further, we establish that, for binary phase objects, the nth moment scales with the difference of the refractive index decrement to the power of n. Finally, we experimentally demonstrate the utility of the moments by quantitatively determining the particle sizes of a range of powders with a laboratory-based setup.

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.

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.

Phase and absorption retrieval using incoherent X-ray sources.

X-ray phase contrast imaging has overcome the limitations of X-ray absorption imaging in many fields. Particular effort has been directed towards developing phase retrieval methods: These reveal quantitative information about a sample, which is a requirement for performing X-ray phase tomography, allows material identification and better distinction between tissue types, etc. Phase retrieval seems impossible with conventional X-ray sources due to their low spatial coherence. In the only previous example where conventional sources have been used, collimators were employed to produce spatially coherent secondary sources. We present a truly incoherent phase retrieval method, which removes the spatial coherence constraints and employs a conventional source without aperturing, collimation, or filtering. This is possible because our technique, based on the pixel edge illumination principle, is neither interferometric nor crystal based. Beams created by an X-ray mask to image the sample are smeared due to the incoherence of the source, yet we show that their displacements can still be measured accurately, obtaining strong phase contrast. Quantitative information is extracted from only two images rather than a sequence as required by several coherent methods. Our technique makes quantitative phase imaging and phase tomography possible in applications where exposure time and radiation dose are critical. The technique employs masks which are currently commercially available with linear dimensions in the tens of centimeters thus allowing for a large field of view. The technique works at high photon energy and thus promises to deliver much safer quantitative phase imaging and phase tomography in the future.

On the origin of contrast in edge illumination X-ray phase-contrast imaging.

Edge illumination (EI) has emerged as an X-ray phase-contrast imaging (XPCi) modality which could present significant advantages in terms of translation to clinical and laboratory applications. In this paper, we model its signal through the use of the "transport of intensity" equation. The validity conditions for this approach and its relationship with previous theoretical models for EI XPCi are discussed. The proposed model enables a simple estimation of the different contributions to the signal, which is shown to complement previously obtained results. In particular, it allows taking into account the effect of both slowly and rapidly varying refraction angles, corresponding to large and small object features. The derived framework is then used to investigate the effect on the signal of the smoothness of the mask edges, of the blurring from the source size and of the width of the object edge.

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.

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.