Applications of a non-interferometric x-ray phase contrast imaging method with both synchrotron and conventional sources

We have developed a totally incoherent, non-interferometric x-ray phase contrast imaging (XPCI) method. This is based on the edge illumination (EI) concept developed at the ELETTRA synchrotron in Italy in the late ‘90s. The method was subsequently adapted to the divergent beam generated by a conventional source, by replicating it for every detector line through suitable masks. The method was modelled both with the simplified ray-tracing and with the more rigorous wave-optics approach, and in both cases excellent agreement with the experimental results was found. The wave-optics model enabled assessing the methods’ coherence requirements, showing that they are at least an order of magnitude more relaxed than in other methods, without this having negative consequences on the phase sensitivity. Our masks have large pitches (up to 50 times larger than in grating interferometry, for example), which allows for manufacturing through standard lithography, scalability, cost-effectiveness and easiness to align. When applied to a polychromatic and divergent beam generated by a conventional source, the method enables the detection of strong phase effects also with uncollimated, unapertured sources with focal spots of up to 100 mm, compatible with the state-of-the-art in mammography. When used at synchrotrons, it enables a contrast increase of orders of magnitude over other methods. Robust phase retrieval was proven for both coherent and incoherent sources, and additional advantages are compatibility with high x-ray energies and easy implementation of phase sensitivity in two directions simultaneously. This paper briefly summarizes these achievements and reviews some of the key results

Proof-of-concept demonstration of edge-illumination x-ray phase contrast imaging combined with tomosynthesis.

In this note we present the first proof-of-concept results on the potential effectiveness of the edge-illumination x-ray phase contrast method (in its 'coded-aperture' based lab implementation) combined with tomosynthesis. We believe that, albeit admittedly preliminary (e.g. we only present phantom work), these results deserve early publication in a note primarily for four reasons. First, we fully modelled the imaging acquisition method, and validated the simulation directly with experimental results. This shows that the implementation of the method in the new geometry is understood, and thus that it will be possible to use the model to simulate more complex scenarios in the future. Secondly, we show that a strong phase contrast signal is preserved in the reconstructed tomosynthesis slices: this was a concern, as the high spatial frequency nature of the signal makes it sensitive to any filtration-related procedure. Third, we show that, despite the non-optimized nature of the imaging prototype used, we can perform a full angular scan at acceptable dose levels and with exposure times not excessively distant from what is required by clinical practice. Finally, we discuss how the proposed phase contrast method, unlike other approaches apart from free-space propagation (which however requires a smaller focal spot, thus reducing the flux and increasing exposure times), can be easily implemented in a tomosynthesis geometry suitable for clinical use. In summary, we find that these technical results indicate a high potential for the combination of the two methods. Combining slice separation with detail enhancement provided by phase effects would substantially increase the detectability of small lesions and/or calcifications, which we aim to demonstrate in the next steps of this study

Edge illumination and coded-aperture X-ray phase-contrast imaging: Increased sensitivity at synchrotrons and lab-based translations into medicine, biology and materials science

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

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

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

Mtss1 promotes cell-cell junction assembly and stability through the small GTPase Rac1

Cell-cell junctions are an integral part of epithelia and are often disrupted in cancer cells during epithelial-to-mesenchymal transition (EMT), which is a main driver of metastatic spread. We show here that Metastasis suppressor-1 (Mtss1; Missing in Metastasis, MIM), a member of the IMD-family of proteins, inhibits cell-cell junction disassembly in wound healing or HGF-induced scatter assays by enhancing cell-cell junction strength. Mtss1 not only makes cells more resistant to cell-cell junction disassembly, but also accelerates the kinetics of adherens junction assembly. Mtss1 drives enhanced junction formation specifically by elevating Rac-GTP. Lastly, we show that Mtss1 depletion reduces recruitment of F-actin at cell-cell junctions. We thus propose that Mtss1 promotes Rac1 activation and actin recruitment driving junction maintenance. We suggest that the observed loss of Mtss1 in cancers may compromise junction stability and thus promote EMT and metastasis

Latin American immigrants in Indianapolis: Perceptions of prejudice and discrimination

The article focuses on immigrants’ interactions with the Indiana natives, with emphasis in the city of Indianapolis and its suburbs. More specifically, this study aims at providing an understanding of the experiences of Latin American immigrants with special attention to perceptions of prejudice and discrimination and to feelings of social exclusion. A substantial proportion of Latin American immigrants interviewed indicated that they considered Indiana natives to be prejudiced and that they had personally experienced discrimination. The study reveals specific examples of discrimination experienced by the immigrants at the work place, in housing, in stores, restaurants and by various service providers. The results of the study demonstrate the relevance of the normative and power resource theories to explain prejudice and discrimination

Regulation of N-WASP and the Arp2/3 Complex by Abp1 Controls Neuronal Morphology

Polymerization and organization of actin filaments into complex superstructures is indispensable for structure and function of neuronal networks. We here report that knock down of the F-actin-binding protein Abp1, which is important for endocytosis and synaptic organization, results in changes in axon development virtually identical to Arp2/3 complex inhibition, i.e., a selective increase of axon length. Our in vitro and in vivo experiments demonstrate that Abp1 interacts directly with N-WASP, an activator of the Arp2/3 complex, and releases the autoinhibition of N-WASP in cooperation with Cdc42 and thereby promotes N-WASP-triggered Arp2/3 complex-mediated actin polymerization. In line with our mechanistical studies and the colocalization of Abp1, N-WASP and Arp2/3 at sites of actin polymerization in neurons, we reveal an essential role of Abp1 and its cooperativity with Cdc42 in N-WASP-induced rearrangements of the neuronal cytoskeleton. We furthermore show that introduction of N-WASP mutants lacking the ability to bind Abp1 or Cdc42, Arp2/3 complex inhibition, Abp1 knock down, N-WASP knock down and Arp3 knock down, all cause identical neuromorphological phenotypes. Our data thus strongly suggest that these proteins and their complex formation are important for cytoskeletal processes underlying neuronal network formation

Tikhonov adaptively regularized gamma variate fitting to assess plasma clearance of inert renal markers

The Tk-GV model fits Gamma Variates (GV) to data by Tikhonov regularization (Tk) with shrinkage constant, λ, chosen to minimize the relative error in plasma clearance, CL (ml/min). Using 169Yb-DTPA and 99mTc-DTPA (n = 46, 8–9 samples, 5–240 min) bolus-dilution curves, results were obtained for fit methods: (1) Ordinary Least Squares (OLS) one and two exponential term (E1 and E2), (2) OLS-GV and (3) Tk-GV. Four tests examined the fit results for: (1) physicality of ranges of model parameters, (2) effects on parameter values when different data subsets are fit, (3) characterization of residuals, and (4) extrapolative error and agreement with published correction factors. Test 1 showed physical Tk-GV results, where OLS-GV fits sometimes-produced nonphysical CL. Test 2 showed the Tk-GV model produced good results with 4 or more samples drawn between 10 and 240 min. Test 3 showed that E1 and E2 failed goodness-of-fit testing whereas GV fits for t > 20 min were acceptably good. Test 4 showed CLTk-GV clearance values agreed with published CL corrections with the general result that CLE1 > CLE2 > CLTk-GV and finally that CLTk-GV were considerably more robust, precise and accurate than CLE2, and should replace the use of CLE2 for these renal markers