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).
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.
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.
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.
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.
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.
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.
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