Framework to optimize fixed-length micro-CT systems for propagation-based phase-contrast imaging.

A laboratory X-ray imaging system with a setup that closely resembles commercial micro-CT systems with a fixed source-to-detector distance of ∼90 cm is investigated for single distance propagation-based phase-contrast imaging and computed tomography (CT). The system had a constant source-to-detector distance, and the sample positions were optimized. Initially, a PTFE wire was imaged, both in 2D and 3D, to characterize fringe contrast and spatial resolution for different X-ray source settings and source-to-sample distances. The results were compared to calculated values based on theoretical models and to simulated (wave-optics based) results, with good agreement being found. The optimization of the imaging system is discussed. CT scans of two biological samples, a tissue-engineered esophageal scaffold and a rat heart, were then acquired at the optimum parameters, demonstrating that significant image quality improvements can be obtained with widely available components placed inside fixed-length cabinets through proper optimization of propagation-based phase-contrast.

On the equivalence of the X-ray scattering retrieval with beam tracking and analyser-based imaging using a synchrotron source.

X-ray phase contrast imaging (XPCI) methods give access to contrast mechanisms that are based on the refractive properties of matter on top of the absorption coefficient in conventional x-ray imaging. Ultra small angle x-ray scattering (USAXS) is a phase contrast mechanism that arises due to multiple refraction events caused by physical features of a scale below the physical resolution of the used imaging system. USAXS contrast can therefore give insight into subresolution structural information, which is an ongoing research topic in the vast field of different XPCI techniques. In this study, we quantitatively compare the USAXS signal retrieved by the beam tracking XPCI technique with the gold standard of the analyzer based imaging XPCI technique using a synchrotron x-ray source. We find that, provided certain conditions are met, the two methods measure the same quantity.

X-ray Phase-Contrast Radiography and Tomography with a Multiaperture Analyzer.

We present a multiaperture analyzer setup for performing x-ray phase contrast imaging in planar and three-dimensional modalities. The method is based on strongly structuring the x-ray beam with an amplitude modulator, before it reaches the sample, and on a multiaperture analyzing element before detection. A multislice representation of the sample is used to establish a quantitative relation between projection images and the corresponding three-dimensional distributions, leading to successful tomographic reconstruction. Sample absorption, phase, and scattering are retrieved from the measurement of five intensity projections. The method is tested on custom-built phantoms with synchrotron radiation: sample absorption and phase can be reliably retrieved also in combination with strong scatterers, simultaneously attaining high sensitivity and dynamic range.

Theory and preliminary experimental verification of quantitative edge illumination x-ray phase contrast tomography.

X-ray phase contrast imaging (XPCi) methods are sensitive to phase in addition to attenuation effects and, therefore, can achieve improved image contrast for weakly attenuating materials, such as often encountered in biomedical applications. Several XPCi methods exist, most of which have already been implemented in computed tomographic (CT) modality, thus allowing volumetric imaging. The Edge Illumination (EI) XPCi method had, until now, not been implemented as a CT modality. This article provides indications that quantitative 3D maps of an object's phase and attenuation can be reconstructed from EI XPCi measurements. Moreover, a theory for the reconstruction of combined phase and attenuation maps is presented. Both reconstruction strategies find applications in tissue characterisation and the identification of faint, weakly attenuating details. Experimental results for wires of known materials and for a biological object validate the theory and confirm the superiority of the phase over conventional, attenuation-based image contrast.

X-ray phase-contrast imaging with nanoradian angular resolution.

We present a new quantitative x-ray phase-contrast imaging method based on the edge illumination principle, which allows achieving unprecedented nanoradian sensitivity. The extremely high angular resolution is demonstrated theoretically and through experimental images obtained at two different synchrotron radiation facilities. The results, achieved at both very high and very low x-ray energies, show that this highly sensitive technique can be efficiently exploited over a very broad range of experimental conditions. This method can open the way to new, previously inaccessible scientific applications in various fields including biology, medicine and materials science.

Identification of a candidate modifying gene for spinal muscular atrophy by comparative genomics.

Spinal muscular atrophy (SMA) is a common recessive disorder characterized by the loss of lower motor neurons in the spinal cord. The disease has been classified into three types based on age of onset and severity. SMA I-III all map to chromosome 5q13 (refs 2,3), and nearly all patients display deletions or gene conversions of the survival motor neuron (SMN1) gene. Some correlation has been established between SMN protein levels and disease course; nevertheless, the genetic basis for SMA phenotypic variability remains unclear, and it has been postulated that the loss of an additional modifying factor contributes to the severity of type I SMA. Using comparative genomics to screen for such a factor among evolutionarily conserved sequences between mouse and human, we have identified a novel transcript, H4F5, which lies closer to SMN1 than any previously identified gene in the region. A multi-copy microsatellite marker that is deleted in more than 90% of type I SMA chromosomes is embedded in an intron of this gene, indicating that H4F5 is also highly deleted in type I SMA chromosomes, and thus is a candidate phenotypic modifier for SMA.

A laboratory-based beam tracking x-ray imaging method achieving two-dimensional phase sensitivity and isotropic resolution with unidirectional undersampling.

Beam tracking X-ray Phase Contrast Imaging is a "Shack-Hartmann" type approach which uses a pre-sample mask to split the x-rays into "beamlets" which are interrogated by a detector with sufficient resolution. The ultimate spatial resolution is determined by the size of the mask apertures, however achieving this resolution level requires "stepping" the sample or the mask in increments equal to the aperture size ("dithering"). If an array of circular apertures is used (which also provides two-dimensional phase sensitivity) instead of long parallel slits, this stepping needs to be carried out in two directions, which lengthens scan times significantly. We present a mask design obtained by offsetting rows of circular apertures, allowing for two-dimensional sensitivity and isotropic resolution while requiring sample or mask stepping in one direction only. We present images of custom-built phantoms and biological specimens, demonstrating that quantitative phase retrieval and near aperture-limited spatial resolutions are obtained in two orthogonal directions.

Post-acquisition mask misalignment correction for edge illumination x-ray phase contrast imaging.

Edge illumination x-ray phase contrast imaging uses a set of apertured masks to translate phase effects into variation of detected intensity. While the system is relatively robust against misalignment, mask movement during acquisition can lead to gradient artifacts. A method has been developed to correct the images by quantifying the misalignment post-acquisition and implementing correction maps to remove the gradient artifact. Images of a woven carbon fiber composite plate containing porosity were used as examples to demonstrate the image correction process. The gradient formed during image acquisition was removed without affecting the image quality, and results were subsequently used for quantification of porosity, indicating that the gradient correction did not affect the quantitative content of the images.

The effect of a variable focal spot size on the contrast channels retrieved in edge-illumination X-ray phase contrast imaging.

Multi-modal X-ray imaging allows the extraction of phase and dark-field (or "Ultra-small Angle Scatter") images alongside conventional attenuation ones. Recently, scan-based systems using conventional sources that can simultaneously output the above three images on relatively large-size objects have been developed by various groups. One limitation is the need for some degree of spatial coherence, achieved either through the use of microfocal sources, or by placing an absorption grating in front of an extended source. Both these solutions limit the amount of flux available for imaging, with the latter also leading to a more complex setup with additional alignment requirements. Edge-illumination partly overcomes this as it was proven to work with focal spots of up to 100 micron. While high-flux, 100 micron focal spot sources do exist, their comparatively large footprint and high cost can be obstacles to widespread translation. A simple solution consists in placing a single slit in front of a large focal spot source. We used a tunable slit to study the system performance at various effective focal spot sizes, by extracting transmission, phase and dark-field images of the same specimens for a range of slit widths. We show that consistent, repeatable results are obtained for varying X-ray statistics and effective focal spot sizes. As the slit width is increased, the expected reduction in the raw differential phase peaks is observed, compensated for in the retrieval process by a broadened sensitivity function. This leads to the same values being correctly retrieved, but with a slightly larger error bar i.e. a reduction in phase sensitivity. Concurrently, a slight increase in the dark-field signal is also observed.

Enhanced detection of threat materials by dark-field x-ray imaging combined with deep neural networks.

X-ray imaging has been boosted by the introduction of phase-based methods. Detail visibility is enhanced in phase contrast images, and dark-field images are sensitive to inhomogeneities on a length scale below the system's spatial resolution. Here we show that dark-field creates a texture which is characteristic of the imaged material, and that its combination with conventional attenuation leads to an improved discrimination of threat materials. We show that remaining ambiguities can be resolved by exploiting the different energy dependence of the dark-field and attenuation signals. Furthermore, we demonstrate that the dark-field texture is well-suited for identification through machine learning approaches through two proof-of-concept studies. In both cases, application of the same approaches to datasets from which the dark-field images were removed led to a clear degradation in performance. While the small scale of these studies means further research is required, results indicate potential for a combined use of dark-field and deep neural networks in security applications and beyond.

Quantitative phase retrieval with picosecond X-ray pulses from the ATF Inverse Compton Scattering source.

Quantitative phase retrieval is experimentally demonstrated using the Inverse Compton Scattering X-ray source available at the Accelerator Test Facility (ATF) in the Brookhaven National Laboratory. Phase-contrast images are collected using in-line geometry, with a single X-ray pulse of approximate duration of one picosecond. The projected thickness of homogeneous samples of various polymers is recovered quantitatively from the time-averaged intensity of transmitted X-rays. The data are in good agreement with the expectations showing that ATF Inverse Compton Scattering source is suitable for performing phase-sensitive quantitative X-ray imaging on the picosecond scale. The method shows promise for quantitative imaging of fast dynamic phenomena.

Note: Design and realization of a portable edge illumination X-ray phase contrast imaging system.

We discuss a portable edge illumination x-ray phase contrast imaging system based on compact piezoelectric motors, which enables its transportation to different environments, e.g., hosting different x-ray source technologies. The analysis of images of standard samples reveals an angular sensitivity of 270 ± 6 nrad, which compares well with the 260 ± 10 nrad reported for previous systems based on stepper motors, demonstrating that system portability can be achieved without affecting phase sensitivity. The results can also be considered a test of the performance of the piezoelectric motors, and as such could be of interest to researchers planning their use in other imaging systems.

Evaluation of microbubble contrast agents for dynamic imaging with x-ray phase contrast.

X-rays are commonly used as a means to image the inside of objects opaque to visible light, as their short wavelength allows penetration through matter and the formation of high spatial resolution images. This physical effect has found particular importance in medicine where x-ray based imaging is routinely used as a diagnostic tool. Increasingly, however, imaging modalities that provide functional as well as morphological information are required. In this study the potential to use x-ray phase based imaging as a functional modality through the use of microbubbles that can be targeted to specific biological processes is explored. We show that the concentration of a microbubble suspension can be monitored quantitatively whilst in flow using x-ray phase contrast imaging. This could provide the basis for a dynamic imaging technique that combines the tissue penetration, spatial resolution, and high contrast of x-ray phase based imaging with the functional information offered by targeted imaging modalities.

Monte Carlo model of a polychromatic laboratory based edge illumination x-ray phase contrast system.

A Monte Carlo model of a polychromatic laboratory based (coded aperture) edge illumination x-ray phase contrast imaging system has been developed and validated against experimental data. The ability for the simulation framework to be used to model two-dimensional images is also shown. The Monte Carlo model has been developed using the McXtrace engine and is polychromatic, i.e., results are obtained through the use of the full x-ray spectrum rather than an effective energy. This type of simulation can in future be used to model imaging of objects with complex geometry, for system prototyping, as well as providing a first step towards the development of a simulation for modelling dose delivery as a part of translating the imaging technique for use in clinical environments.

Low-dose phase contrast tomography with conventional x-ray sources.

PURPOSE: The edge illumination (EI) x-ray phase contrast imaging (XPCi) method has been recently further developed to perform tomographic and, thus, volumetric imaging. In this paper, the first tomographic EI XPCi images acquired with a conventional x-ray source at dose levels below that used for preclinical small animal imaging are presented. METHODS: Two test objects, a biological sample and a custom-built phantom, were imaged with a laboratory-based EI XPCi setup in tomography mode. Tomographic maps that show the phase shift and attenuating properties of the object were reconstructed, and analyzed in terms of signal-to-noise ratio and quantitative accuracy. Dose measurements using thermoluminescence devices were performed. RESULTS: The obtained images demonstrate that phase based imaging methods can provide superior results compared to attenuation based modalities for weakly attenuating samples also in 3D. Moreover, and, most importantly, they demonstrate the feasibility of low-dose imaging. In addition, the experimental results can be considered quantitative within the constraints imposed by polychromaticity. CONCLUSIONS: The results, together with the method's dose efficiency and compatibility with conventional x-ray sources, indicate that tomographic EI XPCi can become an important tool for the routine imaging of biomedical samples.

Sensitivity of edge illumination X-ray phase-contrast imaging.

Recently, we developed a theoretical model that can predict the signal-to-noise ratio for edge-like features in phase-contrast images. This model was then applied for the estimation of the sensitivity of three different X-ray phase-contrast techniques: propagation-based imaging, analyser-based imaging and grating interferometry. We show here how the same formalism can be used also in the case of the edge illumination (EI) technique, providing results that are consistent with those of a recently developed method for the estimation of noise in the retrieved refraction image. The new model is then applied to calculate, in the case of a given synchrotron radiation set-up, the optimum positions of the pre-sample aperture and detector edge to maximize the sensitivity. Finally, an example of the extremely high angular resolution achievable with the EI technique is presented.

Medicine, material science and security: the versatility of the coded-aperture approach.

The principal limitation to the widespread deployment of X-ray phase imaging in a variety of applications is probably versatility. A versatile X-ray phase imaging system must be able to work with polychromatic and non-microfocus sources (for example, those currently used in medical and industrial applications), have physical dimensions sufficiently large to accommodate samples of interest, be insensitive to environmental disturbances (such as vibrations and temperature variations), require only simple system set-up and maintenance, and be able to perform quantitative imaging. The coded-aperture technique, based upon the edge illumination principle, satisfies each of these criteria. To date, we have applied the technique to mammography, materials science, small-animal imaging, non-destructive testing and security. In this paper, we outline the theory of coded-aperture phase imaging and show an example of how the technique may be applied to imaging samples with a practically important scale.

Method for automatization of the alignment of a laboratory based x-ray phase contrast edge illumination system.

Here we present a general alignment algorithm for an edge illumination x-ray phase contrast imaging system, which is used with the laboratory systems developed at UCL. It has the flexibility to be used with all current mask designs, and could also be applied to future synchrotron based systems. The algorithm has proved to be robust experimentally, and can be used for the automatization of future commercial systems through automatic alignment and alignment correction.

Low-dose phase contrast mammography with conventional x-ray sources.

PURPOSE: To provide an x-ray phase contrast imaging (XPCI) method working with conventional sources that could be readily translated into clinical practice. XPCI shows potential in synchrotron studies but attempts at translating it for use with conventional sources are subject to limitations in terms of field of view, stability, exposure time, and possibly most importantly, delivered dose. METHODS: Following the adaptation of our "edge-illumination" XPCI technique for use with conventional x-ray sources through the use of x-ray masks, the authors have further modified the design of such masks to allow further reducing the dose delivered to the sample without affecting the phase sensitivity of the method. RESULTS: The authors have built a prototype based on the new mask design and used it to image ex vivo breast tissue samples containing malignant lesions. The authors compared images acquired with this prototype to those obtained with a conventional system. The authors demonstrate and quantify image improvements, especially in terms of microcalcification detection. On calcifications detected also by the conventional system, the authors measure contrast increases from five to nine fold; calcifications and other features were also detected which are completely invisible in the conventional image. Dose measurements confirmed that the above enhancements were achieved while delivering doses compatible with clinical practice. CONCLUSIONS: The authors obtained phase-related image enhancements in mammography by means of a system built with components available off-the-shelf that operates under exposure time and dose conditions compatible with clinical practice. This opens the way to a straightforward translation of phase enhanced imaging methods into clinical practice.