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Goal-directed behaviour requires mental representations that encode instrumental relationships between actions and their outcomes. The present study investigated how people acquire representations of joint actions where co-actors perform synchronized action contributions to produce joint outcomes in the environment. Adapting an experimental procedure to assess individual action-outcome learning, we tested whether co-acting individuals link jointly produced action outcomes to individual-level features of their own action contributions or to group-level features of their joint action instead. In a learning phase, pairs of participants produced musical chords by synchronizing individual key press responses. In a subsequent test phase, the previously produced chords were presented as imperative stimuli requiring forced-choice responses by both pair members. Stimulus-response mappings were systematically manipulated to be either compatible or incompatible with the individual and joint action-outcome mappings of the preceding learning phase. Only joint but not individual compatibility was found to modulate participants' performance in the test phase. Yet, opposite to predictions of associative accounts of action-outcome learning, jointly incompatible mappings between learning and test phase resulted in better performance. We discuss a possible explanation of this finding, proposing that pairs' group-level learning experience modulated how participants encoded ambiguous task instructions in the test phase. Our findings inform current debates about mechanistic explanations of action-outcome learning effects and provide novel evidence that joint action is supported by dedicated mental representations encoding own and others' actions on a group level., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Klebsiella (K.) pneumoniae is a ubiquitous Gram-negative bacterium and a common coloniser of animals and humans. Today, K. pneumoniae is one of the most persistent nosocomial pathogens worldwide and poses a severe threat/burden to public health by causing urinary tract infections, pneumonia and bloodstream infections. Infections mainly affect immunocompromised individuals and hospitalised patients. In recent years, a new type of K. pneumoniae has emerged associated with community-acquired infections such as pyogenic liver abscess in otherwise healthy individuals and is therefore termed hypervirulent K. pneumoniae (hvKp). The aim of this study was the characterisation of K. pneumoniae isolates with properties of hypervirulence from Germany., Methods: A set of 62 potentially hypervirulent K. pneumoniae isolates from human patients was compiled. Inclusion criteria were the presence of at least one determinant that has been previously associated with hypervirulence: (I) clinical manifestation, (II) a positive string test as a marker for hypermucoviscosity, and (III) presence of virulence associated genes rmpA and/or rmpA2 and/or magA. Phenotypic characterisation of the isolates included antimicrobial resistance testing by broth microdilution. Whole genome sequencing (WGS) was performed using Illumina® MiSeq/NextSeq to investigate the genetic repertoire such as multi-locus sequence types (ST), capsule types (K), further virulence associated genes and resistance genes of the collected isolates. For selected isolates long-read sequencing was applied and plasmid sequences with resistance and virulence determinants were compared., Results: WGS analyses confirmed presence of several signature genes for hvKp. Among them, the most prevalent were the siderophore loci iuc and ybt and the capsule regulator genes rmpA and rmpA2. The most dominant ST among the hvKp isolates were ST395 capsule type K2 and ST395 capsule type K5; both have been described previously and were confirmed by our data as multidrug-resistant (MDR) isolates. ST23 capsule type K1 was the second most abundant ST in this study; this ST has been described as commonly associated with hypervirulence. In general, resistance to beta-lactams caused by the production of extended-spectrum beta-lactamases (ESBL) and carbapenemases was observed frequently in our isolates, confirming the threatening rise of MDR-hvKp strains., Conclusions: Our study results show that K. pneumoniae strains that carry several determinants of hypervirulence are present for many years in Germany. The detection of carbapenemase genes and hypervirulence associated genes on the same plasmid is highly problematic and requires intensified screening and molecular surveillance. However, the non-uniform definition of hvKp complicates their detection. Testing for hypermucoviscosity alone is not specific enough to identify hvKp. Thus, we suggest that the classification of hvKp should be applied to isolates that not only fulfil phenotypical criteria (severe clinical manifestations, hypermucoviscosity) but also (I) the presence of at least two virulence loci e.g. iuc and ybt, and (II) the presence of rmpA and/or rmpA2., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Drug-mediated immune hemolysis is a rare but potentially life-threatening condition. Based on a case of penicillin-induced immune hemolysis, a structured literature review of case reports and studies on penicillin-mediated Drug-Induced Immune Hemolytic Anemia (DIIHA) was carried out., Case Report: A 28-year-old male patient presented to the emergency department with gross hematuria and non-specific abdominal complaints. The patient had a 10-day history of respiratory infection with bacterial tonsillitis, treated orally with penicillin V on an outpatient basis. Laboratory diagnostics detected pathologically altered direct and indirect hemolysis parameters. After stopping the medication, the patient's condition could be stabilized., Conclusion: Diagnosis of penicillin-mediated immune hemolysis requires structured cooperation between clinic and laboratory, as clinical and serological findings may be highly variable with the risk of misdiagnosis. Due to the rarity of the disease, this case report is intended to raise awareness with respect to the triad of abrupt drop in hemoglobin levels in connection with drug therapy and in combination with a strongly positive direct Coombs test., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: The differentiation of minimal-fat-or low-fat-angiomyolipomas from other renal lesions is clinically challenging in conventional computed tomography. In this work, we have assessed the potential of grating-based x-ray phase-contrast computed tomography (GBPC-CT) for visualization and quantitative differentiation of minimal-fat angiomyolipomas (mfAMLs) and oncocytomas from renal cell carcinomas (RCCs) on ex vivo renal samples., Materials and Methods: Laboratory GBPC-CT was performed at 40 kVp on 28 ex vivo kidney specimens including five angiomyolipomas with three minimal-fat (mfAMLs) and two high-fat (hfAMLs) subtypes as well as three oncocytomas and 20 RCCs with eight clear cell (ccRCCs), seven papillary (pRCCs) and five chromophobe RCC (chrRCC) subtypes. Quantitative values of conventional Hounsfield units (HU) and phase-contrast Hounsfield units (HUp) were determined and histogram analysis was performed on GBPC-CT and grating-based attenuation-contrast computed tomography (GBAC-CT) slices for each specimen. For comparison, the same specimens were imaged at a 3T magnetic resonance imaging (MRI) scanner., Results: We have successfully matched GBPC-CT images with clinical MRI and histology, as GBPC-CT presented with increased soft tissue contrast compared to absorption-based images. GBPC-CT images revealed a qualitative and quantitative difference between mfAML samples (58±4 HUp) and oncocytomas (44±10 HUp, p = 0.057) and RCCs (ccRCCs: 40±12 HUp, p = 0.012; pRCCs: 43±9 HUp, p = 0.017; chrRCCs: 40±7 HUp, p = 0.057) in contrast to corresponding laboratory attenuation-contrast CT and clinical MRI, although not all differences were statistically significant. Due to the heterogeneity and lower signal of oncocytomas, quantitative differentiation of the samples based on HUp or in combination with HUs was not possible., Conclusions: GBPC-CT allows quantitative differentiation of minimal-fat angiomyolipomas from pRCCs and ccRCCs in contrast to absorption-based imaging and clinical MRI., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Birnbacher et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Bacterial infections caused by Listeria monocytogenes are rarely observed in routine clinical practice. Symptoms can range from comparatively unspecific to severe, septic courses of disease with cardiac, pulmonary, abdominal or bone involvement., Case Report: A 74-year-old male patient with a history of mitral valve replacement and pacemaker implantation presented to the emergency department with high fever and disturbed coagulation. Transesophageal echocardiography revealed mitral valve endocarditis with early abscess formation. In blood cultures, growth of Listeria monocytogenes was detected after 20 h. Despite immediately initiated calculated antibiotic therapy and following adaption to the resistogram, the mitral valve finding was progressive and cardiosurgical intervention became necessary., Conclusion: Diagnosis of endocarditis caused by Listeria requires structured collaboration between cardiologists, imaging and laboratory. This case report aims to increase awareness of potentially Listeria-induced organ manifestations., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objective: Aim of this study was, to demonstrate the feasibility of high-resolution grating-based X-ray phase-contrast computed tomography (PCCT) for quantitative assessment of cartilage., Materials and Methods: In an experimental setup, 12 osteochondral samples were harvested from n = 6 bovine knees (n = 2 each). From each knee, one cartilage sample was degraded using 2.5% Trypsin. In addition to PCCT and biomechanical cartilage stiffness measurements, 3T and 7T MRI was performed including MSME SE T2 and ME GE T2* mapping sequences for relaxationtime measurements. Paired t-tests and receiver operating characteristics (ROC) curves were used for statistical analyses., Results: PCCT provided high-resolution images for improved morphological cartilage evaluation as compared to 3T and 7T MRI. Quantitative analyses revealed significant differences between the superficial and the deep cartilage layer for T2 mapping as well as for PCCT (P<0.05). No significant difference was detected for PCCT between healthy and degraded samples (P>0.05). MRI and stiffness measurements showed significant differences between healthy and degraded osteochondral samples. Accuracy in the prediction of cartilage degradation was excellent for MRI and biomechanical analyses., Conclusion: In conclusion, high-resolution grating-based X-ray PCCT cartilage imaging is feasible. In addition to MRI and biomechanical analyses it provides complementary, water content independent, information for improved morphological and quantitative characterization of articular cartilage ultrastructure., Competing Interests: This work was supported in part by Arthrex GmbH (Munich, Germany). Dimitrios C. Karampinos and Peter B. Noël receive grant support from Philips Healthcare. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Background: The extent of intraductal carcinoma in situ (DCIS) is commonly underestimated due to the discontinuous growth and lack of microcalcifications. Specimen radiography has been established to reduce the rate of re-excision. However, the predictive value for margin assessment with conventional specimen radiography for DCIS is low. In this study we assessed the potential of grating-based phase-contrast computed tomography (GBPC-CT) at conventional X-ray sources for specimen tomography of DCIS containing samples., Materials and Methods: GBPC-CT was performed on four ex-vivo breast specimens containing DCIS and invasive carcinoma of non-specific type. Phase-contrast and absorption-based datasets were manually matched with corresponding histological slices as the standard of reference., Results: Matching of CT images and histology was successful. GBPC-CT showed an improved soft tissue contrast compared to absorption-based images revealing more histological details in the same sections. Non-calcifying DCIS exceeding the invasive tumor could be correlated to areas of dilated bright ducts around the tumor., Conclusions: GBPC-CT imaging at conventional X-ray sources offers improved depiction quality for the imaging of breast tissue samples compared to absorption-based imaging, allows the identification of diagnostically relevant tissue details, and provides full three-dimensional assessment of sample margins., Competing Interests: The authors have declared that no competing interests exist.

The demand for quantitative medical imaging is increasing in the ongoing digitalization. Conventional computed tomography (CT) is energy-dependent and therefore of limited comparability. In contrast, dual-energy CT (DECT) allows for the determination of absolute image contrast quantities, namely the electron density and the effective atomic number, and is already established in clinical radiology and radiation therapy. Grating-based phase-contrast computed tomography (GBPC-CT) is an experimental X-ray technique that also allows for the measurement of the electron density and the effective atomic number. However, the determination of both quantities is challenging when dealing with polychromatic GBPC-CT setups. In this paper, we present how to calculate the effective atomic numbers with a polychromatic, laboratory GBPC-CT setup operating between 35 and 50\,kVp. First, we investigated the accuracy of the measurement of the attenuation coefficients and electron densities. For this, we performed a calibration using the concept of effective energy. With the reliable experimental quantitative values, we were able to evaluate the effective atomic numbers of the investigated materials using a method previously shown with monochromatic X-ray radiation. In detail, we first calculated the ratio of the electron density and attenuation coefficient, which were experimentally determined with our polychromatic GBPC-CT setup. Second, we compared this ratio with tabulated total attenuation cross sections from literature values to determine the effective atomic numbers. Thus, we were able to calculate two physical absolute quantities -- the electron density and effective atomic number -- that are in general independent of the specific experimental conditions like the X-ray beam spectrum or the setup design.

Grating-based X-ray phase-contrast (gbPC) is an X-ray phase-contrast imaging method involving optical gratings that typically employs the Talbot self-imaging effect. X-ray phase contrast is known to provide significant benefits for biomedical imaging. To investigate these benefits for gbPC, a high-sensitivity gbPC micro-CT setup for small biological samples has been constructed. A gbPC projection measurement simultaneously retrieves the transmittance, differential-phase and dark-field modalities of a sample. Phase stepping, the most common gbPC acquisition technique, involves several acquisitions at different lateral positions of one of the gratings. The three modalities can then be retrieved by least-squares- or FFT-based methods. Unfortunately, increasing differential-phase sensitivity also leads to an increased magnitude of artifacts introduced during retrieval of the modalities from the phase-stepping data, which limits image quality. Most importantly, processing of phase-stepping data with incorrect stepping positions (i.e., spatial sampling jitter) can introduce artifacts to the modalities. Using data from the high-sensitivity gbPC setup, as well as simulations, we show that an artifact is introduced by the jitter which is correlated with the phase of the stepping curve. We present a theoretical explanation for this correlation by introducing small deviations to an equidistant sampling of a stepping curve and approximating the effect on the calculation of the three gbPC modalities with a first-order Taylor approximation. Finally, we present an algorithm for the detection and removal of these artifacts that exploits these correlations. We show that this algorithm is able to eliminate these artifacts without degrading true image information.

Grating-based phase-contrast computed tomography (GBPC-CT) enables increased soft tissue differentiation, but often suffers from streak artifacts when performing high-sensitivity GBPC-CT of biomedical samples. Current GBPC-CT setups consist of one-dimensional gratings and hence allow to measure only the differential phase-contrast (DPC) signal perpendicular to the direction of the grating lines. Having access to the full two-dimensional DPC signal can strongly reduce streak artefacts showing up as characteristic horizontal lines in the reconstructed images. GBPC-CT with gratings tilted by 45° around the optical axis, combining opposed projections, and reconstructing with filtered backprojection is one method to retrieve the full three-dimensional DPC signal. This approach improves the quality of the tomographic data as already demonstrated at a synchrotron facility. However, additional processing and interpolation is necessary, and the approach fails when dealing with cone-beam geometry setups. In this work, we employ the tilted grating configuration with a laboratory GBPC-CT setup with cone-beam geometry and use statistical iterative reconstruction (SIR) with a forward model accounting for diagonal grating alignment. Our results show a strong reduction of streak artefacts and significant increase in image quality. In contrast to the prior approach our proposed method can be used in a laboratory environment due to its cone-beam compatibility.

Objectives: Grating-based phase-contrast computed tomography (gb-PCCT) relies on x-ray refraction instead of absorption to generate high-contrast images in biological soft tissue. The aim of this study was to evaluate the potential of gb-PCCT for the depiction of structural changes in heart disease., Materials and Methods: Four human heart specimens from patients with hypertensive disease, ischemic disease, dilated heart disease, and cardiac lipomatosis were examined. The gb-PCCT setup consisted of an x-ray tube (40 kV, 70 mA), grating-interferometer, and detector, and allowed simultaneous acquisition of phase- and absorption-contrast data. With histopathology as the standard of reference, myocardium (MC), fibrotic scar (FS), interstitial fibrosis (IF), and fatty tissue (FT) were visually and quantitatively evaluated. Systematic differences in absorption- and phase-contrast Hounsfield units (HUabs and HUp) were assessed., Results: Thirteen corresponding cross-sections were included, and MC, FS, IF, and FT were found in 13 (100%), 4 (30.8%), 7 (53.8%), and 13 (100%) cross-sections, respectively. Mean HUp/HUabs were 52.5/54.1, 86.6/69.7, 62.4/62.3, and -38.6/-258.9 for MC, FS, IF, and FT, respectively. An overlap in HUabs was observed for MC and IF (P = 0.84) but not for HUp (P < 0.01). Contrast-to-noise ratios were significantly higher in phase- than in absorption-contrast for MC/FT (35.4 vs 7.8; P < 0.01) and for MC/FS (12.3 vs 0.2; P < 0.01)., Conclusions: Given its superior soft tissue contrast, gb-PCCT is able to depict structural changes in different cardiomyopathies, which can currently not be obtained by x-ray absorption-based imaging methods. If current technical limitations can be overcome, gb-PCCT may evolve as a powerful tool for the anatomical assessment of cardiomyopathy.

Phase-contrast x-ray computed tomography (PCCT) is currently investigated as an interesting extension of conventional CT, providing high soft-tissue contrast even if examining weakly absorbing specimen. Until now, the potential for dose reduction was thought to be limited compared to attenuation CT, since meaningful phase retrieval fails for scans with very low photon counts when using the conventional phase retrieval method via phase stepping. In this work, we examine the statistical behaviour of the reverse projection method, an alternative phase retrieval approach and compare the results to the conventional phase retrieval technique. We investigate the noise levels in the projections as well as the image quality and quantitative accuracy of the reconstructed tomographic volumes. The results of our study show that this method performs better in a low-dose scenario than the conventional phase retrieval approach, resulting in lower noise levels, enhanced image quality and more accurate quantitative values. Overall, we demonstrate that the lower statistical limit of the phase stepping procedure as proposed by recent literature does not apply to this alternative phase retrieval technique. However, further development is necessary to overcome experimental challenges posed by this method which would enable mainstream or even clinical application of PCCT.

Objectives: Dark-field imaging based on small angle X-ray scattering has been shown to be highly sensitive for microcalcifications, e.g. in breast tissue. We hypothesized (i) that high signal areas in dark-field imaging of atherosclerotic plaque are associated with microcalcifications and (ii) that dark-field imaging is more sensitive for microcalcifications than attenuation-based imaging., Methods: Fifteen coronary artery specimens were examined at an experimental set-up consisting of X-ray tube (40kV), grating-interferometer and detector. Tomographic dark-field-, attenuation-, and phase-contrast data were simultaneously acquired. Histopathology served as standard of reference. To explore the potential of dark field imaging in a full-body CT system, simulations were carried out with spherical calcifications of different sizes to simulate small and intermediate microcalcifications., Results: Microcalcifications were present in 10/10 (100%) cross-sections with high dark-field signal and without evidence of calcifications in attenuation- or phase contrast. In positive controls with high signal areas in all three modalities, 10/10 (100%) cross-sections showed macrocalcifications. In negative controls without high signal areas, no calcifications were detected. Simulations showed that the microcalcifications generate substantially higher dark-field than attenuation signal., Conclusions: Dark-field imaging is highly sensitive for microcalcifications in coronary atherosclerotic plaque and might provide complementary information in the assessment of plaque instability., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Current clinical imaging methods face limitations in the detection and correct characterization of different subtypes of renal cell carcinoma (RCC), while these are important for therapy and prognosis. The present study evaluates the potential of grating-based X-ray phase-contrast computed tomography (gbPC-CT) for visualization and characterization of human RCC subtypes. The imaging results for 23 ex vivo formalin-fixed human kidney specimens obtained with phase-contrast CT were compared to the results of the absorption-based CT (gbCT), clinical CT and a 3T MRI and validated using histology. Regions of interest were placed on each specimen for quantitative evaluation. Qualitative and quantitative gbPC-CT imaging could significantly discriminate between normal kidney cortex (54 ± 4 HUp) and clear cell (42 ± 10), papillary (43 ± 6) and chromophobe RCCs (39 ± 7), p < 0.05 respectively. The sensitivity for detection of tumor areas was 100%, 50% and 40% for gbPC-CT, gbCT and clinical CT, respectively. RCC architecture like fibrous strands, pseudocapsules, necrosis or hyalinization was depicted clearly in gbPC-CT and was not equally well visualized in gbCT, clinical CT and MRI. The results show that gbPC-CT enables improved discrimination of normal kidney parenchyma and tumorous tissues as well as different soft-tissue components of RCCs without the use of contrast media.

Purpose: X-ray phase-contrast imaging (PCI) provides additional information beyond absorption characteristics by detecting the phase shift of the X-ray beam passing through material. The grating-based system works with standard polychromatic X-ray sources, promising a possible clinical implementation. PCI has been shown to provide additional information in soft-tissue samples. The aim of this study was to determine if ex vivo quantitative phase-contrast computed tomography (PCCT) may differentiate between pathologic fluid collections., Materials and Methods: PCCT was performed with the grating interferometry method. A protein serial dilution, human blood samples and 17 clinical samples of pathologic fluid retentions were imaged and correlated with clinical chemistry measurements. Conventional and phase-contrast tomography images were reconstructed. Phase-contrast Hounsfield Units (HUp) were used for quantitative analysis analogously to conventional HU. The imaging was analyzed using overall means, ROI values as well as whole-volume-histograms and vertical gradients. Contrast to noise ratios were calculated between different probes and between imaging methods., Results: HUp showed a very good linear correlation with protein concentration in vitro. In clinical samples, HUp correlated rather well with cell count and triglyceride content. PCI was better than absorption imaging at differentiating protein concentrations in the protein samples as well as at differentiating blood plasma from cellular components. PCI also allowed for differentiation of watery samples (such as lymphoceles) from pus., Conclusion: Phase-contrast computed tomography is a promising tool for the differentiation of pathologic fluids that appear homogenous with conventional attenuation imaging., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To evaluate the potential of grating-based phase-contrast computed-tomography (gb-PCCT) to classify human carotid and coronary atherosclerotic plaques according to modified American Heart Association (AHA) criteria., Methods: Experiments were carried out at a laboratory-based set-up consisting of X-ray tube (40 kVp), grating-interferometer and detector. Eighteen human carotid and coronary artery specimens were examined. Histopathology served as the standard of reference. Vessel cross-sections were classified as AHA lesion type I/II, III, IV/V, VI, VII or VIII plaques by two independent reviewers blinded to histopathology. Conservative measurements of diagnostic accuracies for the detection and differentiation of plaque types were evaluated., Results: A total of 127 corresponding gb-PCCT/histopathology sections were analyzed. Based on histopathology, lesion type I/II was present in 12 (9.5 %), III in 18 (14.2 %), IV/V in 38 (29.9 %), VI in 16 (12.6 %), VII in 34 (26.8 %) and VIII in 9 (7.0 %) cross-sections. Sensitivity, specificity and positive and negative predictive value were ≥0.88 for most analyzed plaque types with a good level of agreement (Cohen's kappa = 0.90). Overall, results were better in carotid (kappa = 0.97) than in coronary arteries (kappa = 0.85). Inter-observer agreement was high with kappa = 0.85, p < 0.0001., Conclusions: These results indicate that gb-PCCT can reliably classify atherosclerotic plaques according to modified AHA criteria with excellent agreement to histopathology., Key Points: • Different atherosclerotic plaque types display distinct morphological features in phase-contrast CT. • Phase-contrast CT can detect and differentiate AHA plaque types. • Calcifications caused streak artefacts and reduced sensitivity in type VI lesions. • Overall agreement was higher in carotid than in coronary arteries.

X-ray phase-contrast imaging is an effective approach to drastically increase the contrast and sensitivity of microtomographic techniques. Numerous approaches to depict the real part of the complex-valued refractive index of a specimen are nowadays available. A comparative study using experimental data from grating-based interferometry and propagation-based phase contrast combined with single-distance phase retrieval applied to a non-homogeneous sample is presented (acquired at beamline ID19-ESRF). It is shown that grating-based interferometry can handle density gradients in a superior manner. The study underlines the complementarity of the two techniques for practical applications.

The possibility to perform high-sensitivity X-ray phase-contrast imaging with laboratory grating-based phase-contrast computed tomography (gbPC-CT) setups is of great interest for a broad range of high-resolution biomedical applications. However, achieving high sensitivity with laboratory gbPC-CT setups still poses a challenge because several factors such as the reduced flux, the polychromaticity of the spectrum, and the limited coherence of the X-ray source reduce the performance of laboratory gbPC-CT in comparison to gbPC-CT at synchrotron facilities. In this work, we present our laboratory X-ray Talbot-Lau interferometry setup operating at 40 kVp and describe how we achieve the high sensitivity yet unrivalled by any other laboratory X-ray phase-contrast technique. We provide the angular sensitivity expressed via the minimum resolvable refraction angle both in theory and experiment, and compare our data with other differential phase-contrast setups. Furthermore, we show that the good stability of our high-sensitivity setup allows for tomographic scans, by which even the electron density can be retrieved quantitatively as has been demonstrated in several preclinical studies.

X-ray phase-contrast computed tomography is an emerging imaging technology with powerful capabilities for three-dimensional (3D) visualization of weakly absorbing objects such as biological soft tissues. This technique is an extension of existing X-ray applications because conventional attenuation-contrast images are simultaneously acquired. The complementary information provided by both the contrast modalities suggests that enhanced material characterization is possible when performing combined data analysis. In this study, we describe how protein, lipid, and water concentrations in each 3D voxel can be quantified by vector decomposition. Experimental results of dairy products, porcine fat and rind, and different human soft tissue types are presented. The results demonstrate the potential of phase-contrast imaging as a new analysis tool. The 3D representations of protein, lipid, and water contents open up new opportunities in the fields of biology, medicine, and food science.

Objective: The objective of this study was to assess the potential of grating-based phase-contrast computed tomography (gb-PCCT) for the detection and characterization of human coronary artery disease in an experimental ex vivo validation study., Materials and Methods: The study was approved by the institutional review board, and informed consent was obtained from all patients. Specimens were examined using a conventional low-coherence x-ray tube (40 kV) and a Talbot-Lau grating interferometer. Histopathologic assessment was used as the standard of reference. Signal characteristics of calcified, fibrous (FIB), and lipid-rich (LIP) tissue were visually and quantitatively assessed by phase-contrast Hounsfield units (HU). Conventional absorption-based HU values were also measured. Conservative measurements of diagnostic accuracy for the detection and differentiation of plaque components as well as quantitative measurements of vessel dimensions were obtained, and receiver operating characteristic curve analysis for plaque differentiation was performed., Results: A total of 15 coronary arteries from 5 subjects were available for analysis (386 sections). Calcified, FIB, and LIP displayed distinct gb-PCCT signal criteria. The diagnostic accuracy of gb-PCCT was high with sensitivity, specificity, and negative and positive predictive values of 0.89 or greater for all plaque components with good interrater agreement (к ≥ 0.88). In addition, quantitative measurements of vessel dimensions in gb-PCCT were strongly correlated with measurements obtained from histopathology (Pearson R ≥ 0.86). Finally, phase-contrast Hounsfield units were superior to conventional HU in differentiating FIB and LIP (receiver operating characteristic analysis, 0.86 vs. 0.77, respectively; P < 0.05)., Conclusions: In an ex vivo setting, gb-PCCT provides improved differentiation and quantification of coronary atherosclerotic plaque and may thus serve as a tool for nondestructive histopathology.

X-ray phase-contrast imaging is a novel technology that achieves high soft-tissue contrast. Although its clinical impact is still under investigation, the technique may potentially improve clinical diagnostics. In conventional attenuation-based X-ray computed tomography, radiological diagnostics are quantified by Hounsfield units. Corresponding Hounsfield units for phase-contrast imaging have been recently introduced, enabling a setup-independent comparison and standardized interpretation of imaging results. Thus far, the experimental values of few tissue types have been reported; these values have been determined from fixated tissue samples. This study presents phase-contrast Hounsfield units for various types of non-fixated human soft tissues. A large variety of tissue specimens ranging from adipose, muscle and connective tissues to liver, kidney and pancreas tissues were imaged by a grating interferometer with a rotating-anode X-ray tube and a photon-counting detector. Furthermore, we investigated the effects of formalin fixation on the quantitative phase-contrast imaging results.

Phase-contrast x-ray computed tomography has a high potential to become clinically implemented because of its complementarity to conventional absorption-contrast.In this study, we investigate noise-reducing but resolution-preserving analytical reconstruction methods to improve differential phase-contrast imaging. We apply the non-linear Perona-Malik filter on phase-contrast data prior or post filtered backprojected reconstruction. Secondly, the Hilbert kernel is replaced by regularized iterative integration followed by ramp filtered backprojection as used for absorption-contrast imaging. Combining the Perona-Malik filter with this integration algorithm allows to successfully reveal relevant sample features, quantitatively confirmed by significantly increased structural similarity indices and contrast-to-noise ratios. With this concept, phase-contrast imaging can be performed at considerably lower dose.

The implementation of hybrid fluorescence molecular tomography (FMT) and X-ray computed tomography (CT) has been shown to be a necessary development, not only for combining anatomical with functional and molecular contrast, but also for generating optical images of high accuracy. FMT affords highly sensitive 3-D imaging of fluorescence bio-distribution, but in stand-alone form it offers images of low resolution. It was shown that FMT accuracy significantly improves by considering anatomical priors from CT. Conversely, CT generally suffers from low soft tissue contrast. Therefore utilization of CT data as prior information in FMT inversion is challenging when different internal organs are not clearly differentiated. Instead, we combined herein FMT with emerging X-ray phase-contrast CT (PCCT). PCCT relies on phase shift differences in tissue to achieve soft tissue contrast superior to conventional CT. We demonstrate for the first time FMT-PCCT imaging of different animal models, where FMT and PCCT scans were performed in vivo and ex vivo, respectively. The results show that FMT-PCCT expands the potential of FMT in imaging lesions with otherwise low or no CT contrast, while retaining the cost benefits of CT and simplicity of hybrid device realizations. The results point to the most accurate FMT performance to date.

Background: Fibroadenoma is the most common benign solid breast lesion type and a very common cause for histologic assessment. To justify a conservative therapy, a highly specific discrimination between fibroadenomas and other breast lesions is crucial. Phase-contrast imaging offers improved soft-tissue contrast and differentiability of fine structures combined with the potential of 3-dimensional imaging. In this study we assessed the potential of grating-based phase-contrast CT imaging for visualizing diagnostically relevant features of fibroadenomas., Materials and Methods: Grating-based phase-contrast CT was performed on six ex-vivo formalin-fixed breast specimens containing a fibroadenoma and three samples containing benign changes that resemble fibroadenomas using Talbot Lau interferometry and a polychromatic X-ray source. Phase-contrast and simultaneously acquired absorption-based 3D-datasets were manually matched with corresponding histological slices. The visibility of diagnostically valuable features was assessed in comparison with histology as the gold-standard., Results: In all cases, matching of grating-based phase-contrast CT images and histology was successfully completed. Grating-based phase-contrast CT showed greatly improved differentiation of fine structures and provided accurate depiction of strands of fibrous tissue within the fibroadenomas as well as of the diagnostically valuable dilated, branched ductuli of the fibroadenomas. A clear demarcation of tumor boundaries in all cases was provided by phase- but not absorption-contrast CT., Conclusions: Pending successful translation of the technology to a clinical setting and considerable reduction of the required dose, the data presented here suggest that grating-based phase-contrast CT may be used as a supplementary non-invasive diagnostic tool in breast diagnostics. Phase-contrast CT may thus contribute to the reduction of false positive findings and reduce the recall and core biopsy rate in population-based screening. Phase-contrast CT may further be used to assist during histopathological workup, offering a 3D view of the tumor and helping to identify diagnostically valuable tissue sections within large tumors.

Objective: With an increasing choice of new treatment options, the management of side effects to maintain a chosen treatment if likely to be effective on the tumor remains important. The perception of side effects however varies between the physician and the patient, leading to possible wrong assumptions on tolerability that result in dose modifications, which may ultimately affect effectiveness. The aim was to assess fatigue in patients with advanced or metastatic renal cell carcinoma (RCC) by comparing the evaluation of the physician to the one provided by their respective patient. In addition, we aimed to assess possible influences of fatigue on parameters of quality of life., Methods: Patients receiving systemic treatment for advanced RCC and their physicians were questioned independently regarding incidence and severity of fatigue and its effect on quality of life., Results: Both physicians and patients completed 98 matching questionnaires. Patients were treated with sunitinib, sorafenib, bevacizumab combined with interferon alpha, temsirolimus, everolimus, or interferon alpha alone. Incidence and severity of fatigue was differently assessed by patients and physicians, with fatigue being more severe when reported by the patient. The severity of fatigue increased with progressing treatment lines. Quality of life was significantly lower in patients experiencing fatigue compared with patients without fatigue. Emotional, functional, and physical well-being were all affected by fatigue, the latter being the most affected subscale. Social well-being was least affected., Conclusion: Fatigue is a complex and cumulative condition of patients treated for advanced RCC, and it considerably affects patient's quality of life. As many of its underlying causes may be treated, the divergent perception of occurrence and severity of fatigue should be integrated in treatment concepts. The active role of the patient in helping to manage ailments through assessment should be implemented when optimizing treatment of RCC., (© 2013 Published by Elsevier Inc.)

A new application for the quantitative and isotopic analyses of dissolved inorganic and dissolved organic carbon compounds has been developed. Dissolved organic matter (DOM) in natural water samples can be separated on a high-performance liquid chromatography (HPLC) column and collected as fractions. Each discrete fraction can then be analyzed using the technique of St-Jean (Rapid Commun. Mass Spectrom. 2003; 17: 419-428) with a total inorganic carbon/total organic carbon (TIC/TOC) analyzer interfaced with a continuous-flow isotope ratio mass spectrometer. Experimental data using short-chain fatty acid standards (formic, acetic, and propionic acids) show that fraction recoveries of 100% are possible and that sample integrity is maintained. 13C-isotopic analyses of products prior to and subsequent to extraction and collection show no isotopic effects associated with the methodology, and errors are well within the accepted analytical uncertainty of the IRMS. Comparison of data from pure standards and organic-rich natural waters shows that quantitative analyses still need to be done with standards that more closely imitate the matrices of the samples, in order to acquire an appropriate calibration curve. Injections of organic-rich matrices on the HPLC column did not affect fraction recovery, nor did they create high background of partially retained organic compounds slowly released from the HPLC column, and hence 13C-isotopic results are relatively unaffected. The specific limitation on this methodology is the required use of carbon-free carrier solvents due to potential memory effects associated with the TIC/TOC analyzer. Further developments of this application could make routine compound-specific isotopic analyses (CSIA) for a wider range of organic materials possible.

This paper focuses on the phylogenetic relationships of eight North American caenophidian snake species (Carphophis amoena, Contia tenuis, Diadophis punctatus, Farancia abacura, Farancia erytrogramma, Heterodon nasicus, Heterodon platyrhinos, and Heterodon simus) whose phylogenetic relationships remain controversial. Past studies have referred to these "relict" North American snakes either as colubrid, or as Neotropical dipsadids and/or xenodontids. Based on mitochondrial DNA ribosomal gene sequences and a likelihood-based Bayesian analysis, our study suggests that these North American snakes are not monophyletic and are nested within a group (Dipsadoidea) that contains the Dipsadidae, Xenodontidae, and Natricidae. In addition, we use the relationships proposed here to highlight putative examples of parallel evolution of hemipenial morphology among snake clades.

The extinction of the giant tortoises of the Seychelles Archipelago has long been suspected but is not beyond doubt. A recent morphological study of the giant tortoises of the western Indian Ocean concluded that specimens of two native Seychelles species survive in captivity today alongside giant tortoises of Aldabra, which are numerous in zoos as well as in the wild. This claim has been controversial because some of the morphological characters used to identify these species, several measures of carapace morphology, are reputed to be quite sensitive to captive conditions. Nonetheless, the potential survival of giant tortoise species previously thought extinct presents an exciting scenario for conservation. We used mitochondrial DNA sequences and nuclear microsatellites to examine the validity of the rediscovered species of Seychelles giant tortoises. Our results indicate that the morphotypes suspected to represent Seychelles species do not show levels of variation and genetic structuring consistent with long periods of reproductive isolation. We found no variation in the mitochondrial control region among 55 individuals examined and no genetic structuring in eight microsatellite loci, pointing to the survival of just a single lineage of Indian Ocean tortoises.