X-ray phase and dark-field computed tomography without optical elements.

X-ray diffusive dark-field imaging, which allows spatially unresolved microstructure to be mapped across a sample, is an increasingly popular tool in an array of settings. Here, we present a new algorithm for phase and dark-field computed tomography based on the x-ray Fokker-Planck equation. Needing only a coherent x-ray source, sample, and detector, our propagation-based algorithm can map the sample density and dark-field/diffusion properties of the sample in 3D. Importantly, incorporating dark-field information in the density reconstruction process enables a higher spatial resolution reconstruction than possible with previous propagation-based approaches. Two sample exposures at each projection angle are sufficient for the successful reconstruction of both the sample density and dark-field Fokker-Planck diffusion coefficients. We anticipate that the proposed algorithm may be of benefit in biomedical imaging and industrial settings.

On the quantification of sample microstructure using single-exposure x-ray dark-field imaging via a single-grid setup.

The size of the smallest detectable sample feature in an x-ray imaging system is usually restricted by the spatial resolution of the system. This limitation can now be overcome using the diffusive dark-field signal, which is generated by unresolved phase effects or the ultra-small-angle x-ray scattering from unresolved sample microstructures. A quantitative measure of this dark-field signal can be useful in revealing the microstructure size or material for medical diagnosis, security screening and materials science. Recently, we derived a new method to quantify the diffusive dark-field signal in terms of a scattering angle using a single-exposure grid-based approach. In this manuscript, we look at the problem of quantifying the sample microstructure size from this single-exposure dark-field signal. We do this by quantifying the diffusive dark-field signal produced by 5 different sizes of polystyrene microspheres, ranging from 1.0 to 10.8 µm, to investigate how the strength of the extracted dark-field signal changes with the sample microstructure size, [Formula: see text]. We also explore the feasibility of performing single-exposure dark-field imaging with a simple equation for the optimal propagation distance, given microstructure with a specific size and thickness, and show consistency between this model and experimental data. Our theoretical model predicts that the dark-field scattering angle is inversely proportional to [Formula: see text], which is also consistent with our experimental data.

Directional dark-field retrieval with single-grid x-ray imaging.

Directional dark-field imaging is an emerging x-ray modality that is sensitive to unresolved anisotropic scattering from sub-pixel sample microstructures. A single-grid imaging setup can be used to capture dark-field images by looking at changes in a grid pattern projected upon the sample. By creating analytical models for the experiment, we have developed a single-grid directional dark-field retrieval algorithm that can extract dark-field parameters such as the dominant scattering direction, and the semi-major and -minor scattering angles. We show that this method is effective even in the presence of high image noise, allowing for low-dose and time-sequence imaging.

X-Ray Dark-Field and Phase Retrieval Without Optics, via the Fokker-Planck Equation.

Emerging methods of x-ray imaging that capture phase and dark-field effects are equipping medicine with complementary sensitivity to conventional radiography. These methods are being applied over a wide range of scales, from virtual histology to clinical chest imaging, and typically require the introduction of optics such as gratings. Here, we consider extracting x-ray phase and dark-field signals from bright-field images collected using nothing more than a coherent x-ray source and a detector. Our approach is based on the Fokker-Planck equation for paraxial imaging, which is the diffusive generalization of the transport-of-intensity equation. Specifically, we utilize the Fokker-Planck equation in the context of propagation-based phase-contrast imaging, where we show that two intensity images are sufficient for successful retrieval of both the projected thickness and the dark-field signal associated with the sample. We show the results of our algorithm using both a simulated dataset and an experimental dataset. These demonstrate that the x-ray dark-field signal can be extracted from propagation-based images, and that sample thickness can be retrieved with better spatial resolution when dark-field effects are taken into account. We anticipate the proposed algorithm will be of benefit in biomedical imaging, industrial settings, and other non-invasive imaging applications.

Multimodal intrinsic speckle-tracking (MIST) to extract images of rapidly-varying diffuse X-ray dark-field.

Speckle-based phase-contrast X-ray imaging (SB-PCXI) can reconstruct high-resolution images of weakly-attenuating materials that would otherwise be indistinguishable in conventional attenuation-based X-ray imaging. The experimental setup of SB-PCXI requires only a sufficiently coherent X-ray source and spatially random mask, positioned between the source and detector. The technique can extract sample information at length scales smaller than the imaging system's spatial resolution; this enables multimodal signal reconstruction. "Multimodal Intrinsic Speckle-Tracking" (MIST) is a rapid and deterministic formalism derived from the paraxial-optics form of the Fokker-Planck equation. MIST simultaneously extracts attenuation, refraction, and small-angle scattering (diffusive dark-field) signals from a sample and is more computationally efficient compared to alternative speckle-tracking approaches. Hitherto, variants of MIST have assumed the diffusive dark-field signal to be spatially slowly varying. Although successful, these approaches have been unable to well-describe unresolved sample microstructure whose statistical form is not spatially slowly varying. Here, we extend the MIST formalism such that this restriction is removed, in terms of a sample's rotationally-isotropic diffusive dark-field signal. We reconstruct multimodal signals of two samples, each with distinct X-ray attenuation and scattering properties. The reconstructed diffusive dark-field signals have superior image quality-as measured by the naturalness image quality evaluator, signal-to-noise ratio, and azimuthally averaged power-spectrum-compared to our previous approaches which assume the diffusive dark-field to be a slowly varying function of transverse position. Our generalisation may assist increased adoption of SB-PCXI in applications such as engineering and biomedical disciplines, forestry, and palaeontology, and is anticipated to aid the development of speckle-based diffusive dark-field tensor tomography.

Epidemiology of free-living amoebae infections in Africa: a review.

FLA-related conditions are a rare medical occurrence. Despite their rarity, they are considered a public health concern for two reasons: the absence of a regular treatment regimen in the case of central nervous system infections and the fast progression of the symptoms leading to fatal outcomes. A total of 358 articles were retrieved from different databases (91 from PubMed, 26 from NCBI, 138 from Academia, 102 from Science Direct, and one from IJMED). 7 (46.6%) clinical cases came from Egypt, 2 (13.3%) cases of FLA infection came from Nigeria, 3 (20%) cases came from the Gambia, and 1 (6.6%) case was reported from African countries like Algeria, Tunisia, South Africa, and Zambia. Medical conditions caused by free-living amoeba are considered significant public health concerns. These ubiquitous organisms can cause both fatal and debilitating health conditions. Immediate diagnosis of cases and proper hygienic practices are necessary to provide direct medical intervention. They may be the key to reducing the morbidity and mortality rates from FLA-acquired infections. Although several government-led initiatives have been implemented to mitigate a plethora of parasitic diseases, the case of FLA-related conditions in African countries has yet to be realized.

Precise phase retrieval for propagation-based images using discrete mathematics.

The ill-posed problem of phase retrieval in optics, using one or more intensity measurements, has a multitude of applications using electromagnetic or matter waves. Many phase retrieval algorithms are computed on pixel arrays using discrete Fourier transforms due to their high computational efficiency. However, the mathematics underpinning these algorithms is typically formulated using continuous mathematics, which can result in a loss of spatial resolution in the reconstructed images. Herein we investigate how phase retrieval algorithms for propagation-based phase-contrast X-ray imaging can be rederived using discrete mathematics and result in more precise retrieval for single- and multi-material objects and for spectral image decomposition. We validate this theory through experimental measurements of spatial resolution using computed tomography (CT) reconstructions of plastic phantoms and biological tissues, using detectors with a range of imaging system point spread functions (PSFs). We demonstrate that if the PSF substantially suppresses high spatial frequencies, the potential improvement from utilising the discrete derivation is limited. However, with detectors characterised by a single pixel PSF (e.g. direct, photon-counting X-ray detectors), a significant improvement in spatial resolution can be obtained, demonstrated here at up to 17%.

Experiences of COVID-19-Recovered Healthcare Workers in a Tertiary Hospital in the Philippines: A Mixed-Method Inquiry.

COVID-19 pandemic affected the mental health of the global population. Among the most vulnerable are the healthcare workers (HCWs) who got infected but returned to the frontline after recovery. Currently, there is a dearth of information and understanding on the psychological status and actual lived experience of the recovered HCWs in the Philippines. The present study investigated the psychological status and experiences of 93 COVID-19-recovered HCWs from a tertiary hospital in the Philippines using a mixed-method approach, particularly the explanatory-sequential design. Participants completed the Impact of Event Scale-Revised, and the Depression, Anxiety, and Stress Scale-21 in the quantitative phase. Selected participants took part in focus group discussions in the qualitative phase. Integrated results showed that our participants experienced significant COVID-19-related distress (mean IES-R score = 25.5; partial impact), anxiety (mean subscale score = 7.4; mild), and depression (mean subscale score = 8.1; mild). Certain sociodemographic and professional characteristics and the length of quarantine days appear to affect the psychometric scores. The quantitative results are supported by the participant's description of recovery experiences as living in uncertainty, distress, fatigue, dissociation, and valuation of life. In summary, adequate psychological support and intervention program should be prioritized and provided by hospital management for recovered HCWs to prevent the development of more serious mental health concerns that may significantly affect their tasks in caring for patients and in-hospital management.

Ideal MHD Limited Electron Temperature in Spherical Tokamaks.

It is well documented that the central electron temperature in the national spherical torus experiment (NSTX) remains largely unchanged as the external heating power, and hence the normalized volume averaged plasma pressure ß increases [Stutman, Phys. Rev. Lett. 102, 115002 (2009)PRLTAO0031-900710.1103/PhysRevLett.102.115002]. Here we present a hypothesis that low n, pressure driven ideal magnetohydrodynamic (MHD) instabilities that are nondisruptive, can break magnetic surfaces in the central region and thereby flatten the electron temperature profiles. We demonstrate this mechanism in a 3D resistive MHD simulation of a NSTX discharge. By varying the toroidal magnetic field strength, and/or the heating power, we show that there is a critical value of ß, above which the central temperature profile no longer peaks on axis.

How arts engagement supported social connectedness during the first year of the COVID-19 pandemic in the United Kingdom: findings from the HEartS Survey.

OBJECTIVES: This study investigated how adults in the United Kingdom perceived their arts and cultural engagement to facilitate social connectedness over two phases in the first year of the COVID-19 pandemic. STUDY DESIGN: The study used the HEartS Survey, a newly designed online survey tool to capture arts engagement in the United Kingdom and its associations with social and mental well-being, over two phases in 2020: March to May (Phase 1) and October (Phase 2). METHODS: Qualitative data were provided at both phases by 581 respondents, who identified which arts and cultural activity they felt most connected them to others and how during the last month. RESULTS: Thematic analysis revealed that, at both phases, arts and cultural engagement was perceived to facilitate social connectedness through four pathways that were also identified prepandemic: social opportunities, sharing, feelings of commonality and belonging and collective understanding. The subthemes shed light on specific ways that respondents used the arts during the pandemic to connect with others, including using the arts: as a catalyst for conversations, to maintain, reinstate or strengthen relationships during social distancing and to facilitate social interactions (Theme 1); to bring people together through shared experiences and sharing of art (Theme 2); to elicit feelings of direct and indirect proximity to others, to connect people with common interests, to feel a sense of belonging to something and to feel part of a collective 'COVID-19 experience' or to feel collectively distracted from the pandemic (Theme 3); and to learn from and about other people and to relate to others (Theme 4). The activity most frequently cited as connecting was watching a film or drama, followed by listening to recorded music. CONCLUSIONS: Engagement in arts and cultural activities supported feelings of social connection among adults in the United Kingdom over two phases in the first year of the COVID-19 pandemic, highlighting the importance of access to the arts and culture to support social connectedness.

Quantifying the x-ray dark-field signal in single-grid imaging.

X-ray dark-field imaging reveals the sample microstructure that is unresolved when using conventional methods of x-ray imaging. In this paper, we derive a new method to extract and quantify the x-ray dark-field signal collected using a single-grid imaging set-up, and relate the signal strength to the number of sample microstructures, N. This was achieved by modelling sample-induced changes to the shadow of the upstream grid, and fitting experimental data to this model. Our results suggested that the dark-field scattering angle from our spherical microstructures deviates slightly from the theoretical model of N, which was consistent with results from other experimental methods. We believe the approach outlined here can equip quantitative dark-field imaging of small samples, particularly in cases where only one sample exposure is possible, either due to sample movement or radiation dose limitations. Future directions include an extension into directional dark-field imaging.

Spectral propagation-based x-ray phase-contrast computed tomography.

Purpose: Propagation-based x-ray imaging (PBI) is a phase-contrast technique that is employed in high-resolution imaging by introducing some distance between sample and detector. PBI causes characteristic intensity fringes that have to be processed with appropriate phase-retrieval algorithms, which has historically been a difficult task for objects composed of several different materials. Spectral x-ray imaging has been introduced to PBI to overcome this issue and to potentially utilize the spectral nature of the data for material-specific imaging. We aim to explore the potential of spectral PBI in three-dimensional computed tomography (CT) imaging in this work. Approach: We demonstrate phase-retrieval for experimental high-resolution spectral propagation-based CT data of a simple two-component sample, as well as a multimaterial capacitor test sample. Phase-retrieval was performed using an algorithm based on the Alvarez-Macovski model. Virtual monochromatic (VMI) and effective atomic number images were calculated after phase-retrieval. Results: Phase-retrieval results from the spectral data set show a distinct gray-level for each material with no residual phase-contrast fringes. Several representations of the phase-retrieved data are provided. The VMI is used to display an attenuation-equivalent image at a chosen display energy of 80 keV, to provide good separation of materials with minimal noise. The effective atomic number image shows the material composition of the sample. Conclusions: Spectral photon-counting detector technology has already been shown to be compatible with spectral PBI, and there is a foreseeable need for robust phase-retrieval in high-resolution, spectral x-ray CT in the future. Our results demonstrate the feasibility of phase-retrieval for spectral PBI CT.

Dark-field tomography of an attenuating object using intrinsic x-ray speckle tracking.

Purpose: We investigate how an intrinsic speckle tracking approach to speckle-based x-ray imaging is used to extract an object's effective dark-field (DF) signal, which is capable of providing object information in three dimensions. Approach: The effective DF signal was extracted using a Fokker-Planck type formalism, which models the deformations of illuminating reference beam speckles due to both coherent and diffusive scatter from the sample. Here, we assumed that (a) small-angle scattering fans at the exit surface of the sample are rotationally symmetric and (b) the object has both attenuating and refractive properties. The associated inverse problem of extracting the effective DF signal was numerically stabilized using a "weighted determinants" approach. Results: Effective DF projection images, as well as the DF tomographic reconstructions of the wood sample, are presented. DF tomography was performed using a filtered back projection reconstruction algorithm. The DF tomographic reconstructions of the wood sample provided complementary, and otherwise inaccessible, information to augment the phase contrast reconstructions, which were also computed. Conclusions: An intrinsic speckle tracking approach to speckle-based imaging can tomographically reconstruct an object's DF signal at a low sample exposure and with a simple experimental setup. The obtained DF reconstructions have an image quality comparable to alternative x-ray DF techniques.

Patient-reported outcome measures for a large cohort of serum eye drops recipients in the UK.

INTRODUCTION: Serum eye drops (SED) are an important treatment for patients with chronic and severe ocular surface disease (OSD). Despite a long history of use, there is a paucity of information on patient-reported outcomes, particularly comparing autologous SED (Auto-SED) and allogeneic SED (Allo-SED). National Health Service Blood and Transplant is the national provider of SED service for patients in the UK. PURPOSE: To evaluate and compare patient-reported outcome measures (PROMs) in patients receiving Auto-SED and Allo-SED for severe OSD. MATERIALS AND METHODS: PROMs were retrospectively collected from all new patients commencing treatment with Auto-SED and Allo-SED between January 2017 and September 2018, using the Ocular Surface Disease Index (OSDI) 12-item questionnaire. A linear mixed model was used to evaluate the change in OSDI scores between baseline and follow-up. RESULTS: During the study period, 279 patients who received either Auto-SED (n = 71) or Allo-SED (n = 208) were included in the analysis. Baseline and follow-up OSDI scores were available for 161 of these (49 Auto-SED and 112 Allo-SED). There was a significant reduction in mean OSDI score for both Auto-SED (59.06-24.63, p < 0.001) and Allo-SED (64.21-34.37, p < 0.001). There was no significant difference between Auto-SED and Allo-SED patients in terms of the reduction in the OSDI score (p = 0.27). CONCLUSION: Both Auto-SED and Allo-SED were associated with improvements in the quality of life of patients with chronic and severe OSD. Auto-SED and Allo-SED were equally effective in relieving the symptoms of OSD.

Cediranib in addition to chemotherapy for women with relapsed platinum-sensitive ovarian cancer (ICON6): overall survival results of a phase III randomised trial.

BACKGROUND: Cediranib, an oral anti-angiogenic VEGFR 1-3 inhibitor, was studied at a daily dose of 20 mg in combination with platinum-based chemotherapy and as maintenance in a randomised trial in patients with first relapse of 'platinum-sensitive' ovarian cancer and has been shown to improve progression-free survival (PFS). PATIENTS AND METHODS: ICON6 (NCT00532194) was an international three-arm, double-blind, placebo-controlled randomised trial. Between December 2007 and December 2011, 456 women were randomised, using stratification, to receive either chemotherapy with placebo throughout (arm A, reference); chemotherapy with concurrent cediranib, followed by maintenance placebo (arm B, concurrent); or chemotherapy with concurrent cediranib, followed by maintenance cediranib (arm C, maintenance). Due to an enforced redesign of the trial in September 2011, the primary endpoint became PFS between arms A and C which we have previously published, and the overall survival (OS) was defined as a secondary endpoint, which is reported here. RESULTS: After a median follow-up of 25.6 months, strong evidence of an effect of concurrent plus maintenance cediranib on PFS was observed [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.44-0.72, P < 0.0001]. In this final update of the survival analysis, 90% of patients have died. There was a 7.4-month difference in median survival and an HR of 0.86 (95% CI: 0.67-1.11, P = 0.24) in favour of arm C. There was strong evidence of a departure from the assumption of non-proportionality using the Grambsch-Therneau test (P = 0.0031), making the HR difficult to interpret. Consequently, the restricted mean survival time (RMST) was used and the estimated difference over 6 years by the RMST was 4.8 months (95% CI: -0.09 to 9.74 months). CONCLUSIONS: Although a statistically significant difference in time to progression was seen, the enforced curtailment in recruitment meant that the secondary analysis of OS was underpowered. The relative reduction in the risk of death of 14% risk of death was not conventionally statistically significant, but this improvement and the increase in the mean survival time in this analysis suggest that cediranib may have worthwhile activity in the treatment of recurrent ovarian cancer and that further research should be undertaken.

Quantitative material decomposition using linear iterative near-field phase retrieval dual-energy x-ray imaging.

This paper expands the linear iterative near-field phase retrieval (LIPR) formalism to achieve quantitative material thickness decomposition. Propagation-based phase contrast x-ray imaging with subsequent phase retrieval has been shown to improve the signal-to-noise ratio (SNR) by factors of up to hundreds compared to conventional x-ray imaging. This is a key step in biomedical imaging, where radiation exposure must be kept low without compromising the SNR. However, for a satisfactory phase retrieval from a single measurement, assumptions must be made about the object investigated. To avoid such assumptions, we use two measurements collected at the same propagation distance but at different x-ray energies. Phase retrieval is then performed by incorporating the Alvarez-Macovski (AM) model, which models the x-ray interactions as being comprised of distinct photoelectric and Compton scattering components. We present the first application of dual-energy phase retrieval with the AM model to monochromatic experimental x-ray projections at two different energies for obtaining split x-ray interactions. Our phase retrieval method allows us to separate the object investigated into the projected thicknesses of two known materials. Our phase retrieval output leads to no visible loss in spatial resolution while the SNR improves by factors of 2 to 10. This corresponds to a possible x-ray dose reduction by a factor of 4 to 100, under the Poisson noise assumption.

Material Decomposition Using Spectral Propagation-Based Phase-Contrast X-Ray Imaging.

Material decomposition in X-ray imaging uses the energy-dependence of attenuation to digitally decompose an object into specific constituent materials, generally at the cost of enhanced image noise. Propagation-based X-ray phase-contrast imaging is a developing technique that can be used to reduce image noise, in particular from weakly attenuating objects. In this paper, we combine spectral phase-contrast imaging with material decomposition to both better visualize weakly attenuating features and separate them from overlying objects in radiography. We derive an algorithm that performs both tasks simultaneously and verify it against numerical simulations and experimental measurements of ideal two-component samples composed of pure aluminum and poly(methyl methacrylate). Additionally, we showcase first imaging results of a rabbit kitten's lung. The attenuation signal of a thorax, in particular, is dominated by the strongly attenuating bones of the ribcage. Combined with the weak soft tissue signal, this makes it difficult to visualize the fine anatomical structures across the whole lung. In all cases, clean material decomposition was achieved, without residual phase-contrast effects, from which we generate an un-obstructed image of the lung, free of bones. Spectral propagation-based phase-contrast imaging has the potential to be a valuable tool, not only in future lung research, but also in other systems for which phase-contrast imaging in combination with material decomposition proves to be advantageous.

Spectral x-ray imaging: Conditions under which propagation-based phase-contrast is beneficial.

Energy-resolved attenuation data in spectral x-ray imaging enables material decomposition, in which the different materials inside an object can be identified and separated virtually. Material decomposition has the drawback of increased noise in the resulting material images relative to the measured images. Recently, spectral x-ray imaging was combined with propagation-based x-ray phase-contrast imaging, an x-ray technique that has the potential to greatly reduce image noise by utilizing wave-optical effects. The net combined effects on image noise of performing spectral material decomposition with phase-contrast are not yet well understood, and we provide a detailed theoretical investigation of this topic here. In particular, we investigate how the addition of phase-contrast in spectral imaging affects material decomposition compared to using conventional spectral attenuation data. We show how the underlying equations can be rearranged into parts that resemble low- and high-pass filters on the input images, from which we are able to identify different energy-dependent cases where phase-contrast is or is not advantageous. Our results suggest that the benefits of phase-contrast in the context of material decomposition are primarily restricted to x-ray energies under a certain threshold, where that threshold depends on the given material combination, and sits in a region where photoelectric absorption dominates x-ray attenuation. Additionally, we show that decomposition of the electron density using an image basis spanned by functions of the Alvarez-Macovski model benefits from phase-contrast, regardless of the x-ray energies. All our findings are based purely on theoretical considerations, and can, therefore, be used to determine the feasibility and utility of propagation-based phase-contrast in spectral x-ray imaging ahead of any data collection.

Material decomposition from a single x-ray projection via single-grid phase contrast imaging.

This study describes a new approach for material decomposition in x-ray imaging, utilizing phase contrast both to increase sensitivity to weakly attenuating samples and to act as a complementary measurement to attenuation, therefore allowing two overlaid materials to be separated. The measurements are captured using the single-exposure, single-grid x-ray phase contrast imaging technique, with a novel correction that aims to remove propagation-based phase effects seen at sharp edges in the attenuation image. The use of a single-exposure technique means that images can be collected in a high-speed sequence. Results are shown for both a known two-material sample and for a biological specimen.