Many fields, from aerospace engineering to cultural heritage, can benefit from x-ray micro computed tomography (micro-CT). However, access to x-ray imaging tools remains limited for non-expert users. The UK’s National X-Ray Computed Tomography facility (NXCT) therefore aims to provide access and expert support to academia and industry. As part of the NXCT, at UCL we have developed a unique user facility with multi-scale and multi-contrast x-ray micro-CT capabilities. Our custom system has an x-ray generator with Molybdenum and Copper targets, which can be changed to adapt the energy to the needs of an imaging experiment. The x-rays are emitted on both sides of the source allowing for two imaging stations: one at mm-sized field-of-view (FOV) with resolutions of around 1μm, the “high-resolution station”; and one at cm-sized FOV with resolutions of around 10μm, the “large FOV station”. The high-resolution station is fitted with a custom mirror which gives a monochromatic beam at 17.5keV (for Mo) and 8keV (for Cu). Both stations can be operated with phase-contrast methods such as free-space propagation or beam tracking. Access to this new imaging facility, dedicated to academic and industrial users, is supported through free-at-the-point-of-access and paid schemes.
In recent years, x-ray micro-computed tomography (micro-CT) systems with amplitude modulated beams have gained global interest. These systems feature a modulator, that is, an x-ray opaque mask with periodically spaced apertures, in front of the sample, creating an array of spatially separated beamlets. The approach offers x-ray phase contrast imaging (XPCI), which improves the contrast-to-noise ratio and reveals the presence of sub-resolution inhomogeneities by capturing, respectively, refraction and ultra-small angle scattering (dark field signal) alongside x-ray attenuation. Additionally, the modulator can increase spatial resolution, as the narrow beamlets can transfer higher spatial frequencies without requiring geometric magnification. This brief communication reviews the working principle of the approach and comments on a remaining challenge (relatively long scan times).
A rotating-anode x-ray source and custom-built sCMOS-based detector have been integrated into a lab-based micro-CT system to demonstrate full CT acquisition in as little as 132ms. This has been used to examine the expansion of a polymer foam in 4D, with a temporal resolution of 2Hz. The system is easily adapted to carry out fast phase-sensitive multi-contrast CT with sub-10s CT acquisition times. This is made possible through the beam-tracking technique, which is capable of multi-contrast CT using only a single shot per projection angle, while also being compatible with incoherent sources. This paves the way to dynamic, phase-sensitive, multi-contrast micro-CT in the laboratory.
Tissue engineering (TE) holds promise for generating lab-grown patient specific organs which can provide: (1) effective treatment for conditions that require volumetric tissue transplantation and (2) new platforms for drug testing. Even though volumetric structural information is essential for confirming successful organ maturation, TE protocol designs are currently informed through destructive and 2D construct assessment tools (e.g. histology). X-ray phase-contrast computed-tomography (PC-CT) can generate non-destructive, high resolution, 3D density maps of organ architecture. In this work, PC-CT is used as new imaging tool for guiding two TE protocols currently at the in-vitro testing stage. The first (1) involves cell-repopulation of an oesophageal scaffold, with the aim of using the regenerated construct for treating long-gap oesophageal atresia, whilst for the second (2) a lung-derived scaffold is populated with islets for regenerating a pancreas, with the “repurposed” lung offering a platform for diabetes drug testing. By combing 3D images and quantitative information, we were able to perform comprehensive construct evaluation. Specifically, we assessed volumetrically: (1) the cell-distribution within the regenerated oesophagi and (2) islet integration with the vascular tree of the lung-derived scaffold. This new information was proven to be essential for establishing corresponding TE protocols and enabled their progression to more advanced scale-up models. We are confident that PC-CT will provide the novel insights necessary to further progress TE protocols, with the next step being in-vivo testing. Crucially, the non-destructive nature of PC-CT will allow in-vivo assessments of TE constructs following their implantation into animal hosts, to investigate their successful integration.
X-ray dark-field imaging is used to visualize the ultra-small angle x-ray scattering signal that originates from sub-resolution density fluctuations within the sample microstructure. Dark-field tomography using the edge-illumination x-ray imaging system is presented as a tool for measuring this scattering signal in a sample in three dimensions. Its applicability to different fields is shown through example images of a multi-material phantom, a tissue-engineered esophagus, a pouch cell battery and a short-fiber reinforced composite material. The multichannel contrast available in edge-illumination helps with material identification, with high contrast at boundaries enhancing dark-field reconstructions.
X-ray Phase-Contrast Computed Tomography (PC-CT) increases contrast in weakly attenuating samples, such as soft tissues. In Edge-Illumination (EI) PC-CT, phase effects are accessed from amplitude modulation of the x-ray beam using alternating transmitting and attenuating masks placed prior to the sample and detector. A large field of view PC-CT scanner using this technique was applied to two areas of cancer assessment, namely excised breast and esophageal tissue. For the breast tissue, Wide Local Excisions (WLEs) were studied intra-operatively using PC-CT for the evaluation of tumor removal in breast conservation surgery. Images were acquired in 10 minutes without compromising on image quality, showing this can be used in a clinical setting. Longer, higher resolution PC-CT images were also taken, with analysis showing previously undetected thinning of tumor strands. This would allow a second use of the system for “virtual histopathology”, outside of surgery. For the esophagus samples, tissues were taken from esophagectomy surgery, where the lower part of the esophagus is removed, and the stomach relocated. For the assessment of ongoing therapy, accurate staging of tumors in the removed esophagus is essential, with the current gold standard provided by histopathology. PCCT images were acquired on several samples and compare well with histopathology, with both modalities showing similar features. Examples are shown where staging of tumor penetration is possible with PC-CT images alone, which is hoped will be an important step in performing the imaging and staging intra-operatively.
Tissue imaging is a pivotal component of both biomedical research and clinical practice. In order to identify tissue structures down to the cellular level, it requires the capability to image mm-size unstained tissue specimens with micron to sub-micron resolution. Tissue imaging is normally performed either using x-rays or visible light. While the latter is limited by light scattering in relatively thick tissues, the former often suffers from poor contrast in absorption-based systems. Phase-contrast x-ray microscopes exist but they often lack the required quantitativeness, entail acquisition times of the order of tens of hours for 3-D imaging and are limited to narrow fields of view. We propose a novel multi-modal phase-based x-ray microscope capable of imaging mm-thick tissue samples on a mm-size field of view using intensity-modulation masks. They act as optical elements allowing the quantitative retrieval of tissue properties such as transmission, refraction and scattering. Additionally, given that the system’s spatial resolution depends only on the mask aperture size, a multi-resolution approach is possible by selecting masks with aperture size matching the resolution requirements (micron and sub-micron) of specific samples. The design and optimization of the x-ray microscope is presented in this paper together with exemplar images of a thin foam sample resulting from the retrieval of the three contrast channels. The final paper will include details of the system parameter optimization (e.g., propagation distance, mask aperture and period), their effect on the retrieval algorithm and imaging performance as well as the first images of biological samples.
A preliminary investigation into the use of cycloidal computed tomography for intraoperative specimen imaging is presented. Intraoperative imaging is applied in time-sensitive clinical settings, where obtaining a high-resolution, highquality image within minutes is paramount in evaluating the success of operations and/or the need for additional surgery. As a flexible imaging method that is compatible with x-ray phase contrast imaging, cycloidal computed tomography can provide both high spatial resolution and high image contrast, whilst keeping scan times short thanks to an effective under-sampling approach. To gather early evidence, the method was tested on resected breast and oesophageal tissue. The results, although preliminary, indicate that cycloidal imaging may indeed be beneficial for intraoperative specimen imaging, although further studies are required to confirm this potential.
Owing to their combination of low weight and high strength, carbon fiber reinforced composites are widely used in the aerospace industry, including for primary aircraft structures. Porosity introduced by the manufacturing process can compromise structural performance and integrity, with a maximum porosity content of 2% considered acceptable for many aerospace applications. The main nondestructive evaluation (NDE) techniques used in industry are ultrasonic imaging and X-ray computed tomography, however both techniques have limitations. Edge Illumination X-ray Phase Contrast Imaging (EI XPCi) is a novel technique that exploits the phase effects induced by damage and porosity on the X-ray beam to create improved contrast. EI XPCi is a differential (i.e., sensitive to the first derivative of the phase), multi-modal phase method that uses a set of coded aperture masks to acquire and retrieve the absorption, refraction, and ultra-small-angle scattering signals, the latter arising from sub-pixel sample features. For carbon fiber-reinforced woven composite specimens with varying levels of porosity, porosity quantification obtained through various signals produced by EI XPCi was compared to ultrasonic immersion absorption C-scans and matrix digestion. The standard deviation of the differential phase is introduced as a novel signal for the quantification of porosity in composite plates, with good correlation to ultrasonic attenuation.
Combining low weight and high strength, carbon fiber reinforced composites are widely used in the aerospace industry, including for primary aircraft structures. Barely visible impact damage can compromise the structural integrity and potentially lead to failures. Edge Illumination (EI) X-ray Phase Contrast imaging (XPCi) is a novel X-ray imaging technique that uses the phase effects induced by damage to create improved contrast. For a small cross-ply composite specimen with impact damage, damage detection was compared to ultrasonic immersion C-scans. Different defect types could be located and identified, verified from the conventional ultrasonic NDE measurement.
The design of an X-ray phase contrast tomography system for intra-operative specimen imaging based on edge illumination is presented. The use of edge illumination makes possible working with large focus, polychromatic X-ray sources reducing acquisition times of tomography scans down to values compatible with clinical use, while maintaining phase sensitivity in a compact device. The results collected so far show that application of this technology to breast conservation surgery has great potential to reduce re-operations, thus saving additional costs for healthcare services and stress for patients.
Edge illumination (EI) is an x-ray phase-contrast imaging technique, exploiting sensitivity to x-ray refraction to visualize features, which are often not detected by conventional absorption-based radiography. The method does not require a high degree of spatial coherence and is achromatic and, therefore, can be implemented with both synchrotron radiation and commercial x-ray tubes. Using different retrieval algorithms, information about an object’s attenuation, refraction, and scattering properties can be obtained. In recent years, a theoretical framework has been developed that enables EI computed tomography (CT) and, hence, three-dimensional imaging. This review provides a summary of these advances, covering the development of different image acquisition schemes, retrieval approaches, and applications. These developments constitute an integral part in the transformation of EI CT into a widely spread imaging tool for use in a range of fields.
The implementation of X-Ray Phase Contrast (XPC) imaging at synchrotrons has demonstrated transformative potential on a wide range of applications, from medicine and biology to materials science. However, translation to conventional laboratory sources has proven more problematic, because of XPC’s stringent requirements in terms of spatial coherence. This has imposed the use of either micro-focal sources, or collimators (e.g. source gratings) where sources with extended focal spots were used. This reduces the available x-ray flux leading to long exposure times, which is often exacerbated by the use of additional optical elements that need to be scanned during image acquisition. Where these elements are placed downstream of the object, they also lead to an increase in the delivered dose.
XPC has also been successfully adapted to full 3D, computed tomography (CT) implementations, which has however exacerbated the above concerns in terms of acquisition times and delivered doses.
We tackled this problem by developing an incoherent approach to XPC that works with non micro-focal laboratory sources without requiring any additional collimation. The method uses one or two low aspect ratio x-ray masks that are built on low-absorbing graphite substrates for maximum transmission through the mask apertures. The combination of this with a “single-shot” phase retrieval algorithm has enabled the development of a lab-based XPC-CT system that can perform a full scan in a few minutes while delivering low radiation doses. The talk will briefly describe how the method works, then show application examples including direct comparisons with the synchrotron gold standard.
X-ray imaging is the most commonly used method in baggage screening. Conventional x-ray attenuation (usually in dual-energy mode) is exploited to discriminate threat and non-threat materials: this is essentially, a method that has seen little changes in decades. Our goal is to demonstrate that x-rays can be used in a different way to achieve improved detection of weapons and explosives. Our approach involves the use of x-ray phase contrast and it a) allows much higher sensitivity in the detection of object edges and b) can be made sensitive to the sample’s microstructure. We believe that these additional channels of information, alongside conventional attenuation which would still be available, have the potential to significantly increase both sensitivity and specificity in baggage scanning.
We obtained preliminary data demonstrating the above enhanced detection, and we built a scanner (currently in commissioning) to scale the concept up and test it on real baggage. In particular, while previous X-ray phase contrast imaging systems were limited in terms of both field of view (FOV) and maximum x-ray energy, this scanner overcomes both those limitations and provides FOVs up to 20 to 50 cm2 with x-ray energies up to 100 keV.
In this article we discuss three different developments in Edge Illumination (EI) X-ray phase contrast imaging
(XPCi), all ultimately aimed at optimising EI computed tomography (CT) for use in different environments, and
for different applications. For the purpose of reducing scan times, two approaches are presented; the reverse
projection" acquisition scheme which allows a continuous rotation of the sample, and the single image" retrieval
algorithm, which requires only one frame for retrieval of the projected phase map. These are expected to lead
to a substantial reduction of EI CT scan times, a prospect which is likely to promote the translation of EI into
several applications, including clinical. The last development presented is the "modified local" phase retrieval.
This retrieval algorithm is specifically designed to accurately retrieve sample properties (absorption, refraction,
scattering) in cases where high-resolution scans are required in non-ideal environments. Experimental results,
using both synchrotron radiation and laboratory sources, are shown for the various approaches.
The application of x-ray phase contrast computed tomography (PCT) to the field of tissue engineering is dis- cussed. Specific focus is on the edge illumination PCT method, which can be adapted to weakly coherent x-ray sources, permitting PCT imaging in standard (non-synchrotron) laboratory environments. The method was applied to a prominent research topic in tissue engineering, namely the development of effective and reliable decellularization protocols to derive scaffolds from native tissue. Results show that edge illumination PCT provides sufficient image quality to evaluate the microstructural integrity of scaffolds and, thus, to assess the performance of the used decellularization technique. In order to highlight that edge illumination PCT can ultimately comply with demands on a high specimen throughput and low doses of radiation, recently developed strategies for scan time and dose reduction are discussed.
We report on a new approach to large field-of-view laboratory-based X-ray phase-contrast imaging. The method is based upon the asymmetric mask design that enables the retrieval of the absorption, refraction and ultra-small- angle scattering properties of the sample without the need to move any component of the imaging system. The sample is scanned through the imaging system, which also removes possible aliasing problems that might arise from partial sample illumination when using the edge illumination technique. This concept can be extended to any desired number of apertures providing, at the same time, intensity projections at complementary illumination conditions. Experimental data simultaneously acquired at seven different illumination fractions are presented along with the results obtained from a numerical model that incorporates the actual detector performance. The ultimate shape of the illumination function is shown to be significantly dependent on these detector-specific characteristics. Based on this concept, a large field-of-view system was designed, which is also capable to cope with relatively high (100 kVp) X-ray energies. The imaging system obtained in this way, where the asymmetric mask design enables the data to be collected without moving any element of the instrumentation, adapts particularly well to those situations in medical, industrial and security imaging where the sample has to be scanned through the system.
Edge illumination (EI) X-ray phase-contrast imaging (XPCI) has potential for applications in different fields of research, including materials science, non-destructive industrial testing, small-animal imaging, and medical imaging. One of its main advantages is the compatibility with laboratory equipment, in particular with conventional non-microfocal sources, which makes its exploitation in normal research laboratories possible. In this work, we demonstrate that the signal in laboratory implementations of EI can be correctly described with the use of the simplified geometrical optics. Besides enabling the derivation of simple expressions for the sensitivity and spatial resolution of a given EI setup, this model also highlights the EI’s achromaticity. With the aim of improving image quality, as well as to take advantage of the fact that all energies in the spectrum contribute to the image contrast, we carried out EI acquisitions using a photon-counting energy-resolved detector. The obtained results demonstrate that this approach has great potential for future laboratory implementations of EI.
This article discusses two experimental setups of edge illumination (EI) x-ray phase contrast imaging (XPCi) as well as
the theory that is required to reconstruct quantitative tomographic maps using established methods, e.g. filtered back
projection (FBP). Tomographic EI XPCi provides the option to reconstruct volumetric maps of different physical
quantities, amongst which are the refractive index decrement from unity and the absorption coefficient, which can be
used for dual-mode imaging. EI XPCi scans of a custom-built wire phantom using synchrotron and x-ray tube generated
radiation were carried out, and tomographic maps of both parameters were reconstructed. This article further discusses
the theoretical basis for the tomographic reconstruction of images showing combined phase and attenuation contrast.
Corresponding experimental results are presented.
We present a development of the laboratory-based implementation of edge-illumination (EI) x-ray phase contrast
imaging (XPCI) that simultaneously enables low-dose and high sensitivity. Lab-based EI-XPCI simplifies the set-up
with respect to other methods, as it only requires two optical elements, the large pitch of which relaxes the alignment
requirements. Albeit in the past it was erroneously assumed that this would reduce the sensitivity, we demonstrate
quantitatively that this is not the case.
We discuss a system where the pre-sample mask open fraction is smaller than 50%, and a large fraction of the created
beamlets hits the apertures in the detector mask. This ensures that the majority of photons traversing the sample are
detected i.e. used for image formation, optimizing dose delivery. We show that the sensitivity depends on the dimension
of the part of each beamlet hitting the detector apertures, optimized in the system design. We also show that the aperture
pitch does not influence the sensitivity. Compared to previous implementations, we only reduced the beamlet fraction
hitting the absorbing septa on the detector mask, not the one falling inside the apertures: the same number of x-rays per
second is thus detected, i.e. the dose is reduced, but not at the expense of exposure time.
We also present an extension of our phase-retrieval algorithm enabling the extraction of ultra-small-angle scattering by
means of only one additional frame, with all three frames acquired within dose limits imposed by e.g. clinical
mammography, and easy adaptation to lab-based phase-contrast x-ray microscopy implementations.
The edge illumination principle was first proposed at Elettra (Italy) in the late nineties, as an alternative method
for achieving high phase sensitivity with a very simple and flexible set-up, and has since been under continuous
development in the radiation physics group at UCL. Edge illumination allows overcoming most of the limitations
of other phase-contrast techniques, enabling their translation into a laboratory environment. It is relatively
insensitive to mechanical and thermal instabilities and it can be adapted to the divergent and polychromatic
beams provided by X-ray tubes. This method has been demonstrated to work efficiently with source sizes up
to 100m, compatible with state-of-the-art mammography sources. Two full prototypes have been built and
are operational at UCL. Recent activity focused on applications such as breast and cartilage imaging, homeland
security and detection of defects in composite materials. New methods such as phase retrieval, tomosynthesis
and computed tomography algorithms are currently being theoretically and experimentally investigated. These
results strongly indicate the technique as an extremely powerful and versatile tool for X-ray imaging in a wide
range of applications.
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