Robust Sample Information Retrieval in Dark-Field Computed Tomography with a Vibrating Talbot-Lau Interferometer.

X-ray computed tomography (CT) is a crucial tool for non-invasive medical diagnosis that uses differences in materials' attenuation coefficients to generate contrast and provide 3D information. Grating-based dark-field-contrast X-ray imaging is an innovative technique that utilizes small-angle scattering to generate additional co-registered images with additional microstructural information. While it is already possible to perform human chest dark-field radiography, it is assumed that its diagnostic value increases when performed in a tomographic setup. However, the susceptibility of Talbot-Lau interferometers to mechanical vibrations coupled with a need to minimize data acquisition times has hindered its application in clinical routines and the combination of X-ray dark-field imaging and large field-of-view (FOV) tomography in the past. In this work, we propose a processing pipeline to address this issue in a human-sized clinical dark-field CT prototype. We present the corrective measures that are applied in the employed processing and reconstruction algorithms to mitigate the effects of vibrations and deformations of the interferometer gratings. This is achieved by identifying spatially and temporally variable vibrations in air reference scans. By translating the found correlations to the sample scan, we can identify and mitigate relevant fluctuation modes for scans with arbitrary sample sizes. This approach effectively eliminates the requirement for sample-free detector area, while still distinctly separating fluctuation and sample information. As a result, samples of arbitrary dimensions can be reconstructed without being affected by vibration artifacts. To demonstrate the viability of the technique for human-scale objects, we present reconstructions of an anthropomorphic thorax phantom.

Correction for X-ray Scatter and Detector Crosstalk in Dark-field Radiography.

Dark-field radiography, a new X-ray imaging method, has recently been applied to human chest imaging for the first time. It employs conventional X-ray devices in combination with a Talbot-Lau interferometer with a large field of view, providing both attenuation and dark-field radiographs. It is well known that sample scatter creates artifacts in both modalities. Here, we demonstrate that also X-ray scatter generated by the interferometer as well as detector crosstalk create artifacts in the dark-field radiographs, in addition to the expected loss of spatial resolution. We propose deconvolution-based correction methods for the induced artifacts. The kernel for detector crosstalk is measured and fitted to a model, while the kernel for scatter from the analyzer grating is calculated by a Monte-Carlo simulation. To correct for scatter from the sample, we adapt an algorithm used for scatter correction in conventional radiography. We validate the obtained corrections with a water phantom. Finally, we show the impact of detector crosstalk, scatter from the analyzer grating and scatter from the sample and their successful correction on dark-field images of a human thorax.

Correction for Mechanical Inaccuracies in a Scanning Talbot-Lau Interferometer.

Grating-based X-ray phase-contrast and in particular dark-field radiography are promising new imaging modalities for medical applications. Currently, the potential advantage of dark-field imaging in early-stage diagnosis of pulmonary diseases in humans is being investigated. These studies make use of a comparatively large scanning interferometer at short acquisition times, which comes at the expense of a significantly reduced mechanical stability as compared to tabletop laboratory setups. Vibrations create random fluctuations of the grating alignment, causing artifacts in the resulting images. Here, we describe a novel maximum likelihood method for estimating this motion, thereby preventing these artifacts. It is tailored to scanning setups and does not require any sample-free areas. Unlike any previously described method, it accounts for motion in between as well as during exposures.

X-Ray Dark-Field Signal Reduction Due to Hardening of the Visibility Spectrum.

X-ray dark-field imaging enables a spatially-resolved visualization of ultra-small-angle X-ray scattering. Using phantom measurements, we demonstrate that a material's effective dark-field signal may be reduced by modification of the visibility spectrum by other dark-field-active objects in the beam. This is the dark-field equivalent of conventional beam-hardening, and is distinct from related, known effects, where the dark-field signal is modified by attenuation or phase shifts. We present a theoretical model for this group of effects and verify it by comparison to the measurements. These findings have significant implications for the interpretation of dark-field signal strength in polychromatic measurements.

[New definition and classification of pulmonary hypertension]. / Die neue Definition und Klassifikation der pulmonalen Hypertonie.

In the recent ESC/ERS guidelines on the diagnosis and management of pulmonary hypertension (PH) several important changes have been made in respect of the definition and classification of PH.The mPAP cut-off for defining PH was lowered. PH is now defined by an mPAP > 20 mmHg assessed by right heart catheterization. Moreover, the PVR threshold for defining precapillary PH was lowered. Precapillary PH is now defined by a PVR > 2 WU and a pulmonary arterial wedge pressure (PAWP) ≤ 15 mmHg. Furthermore, the increasing evidence for the clinical relevance of pulmonary exercise hemodynamics led to the reintroduction of exercise pulmonary hypertension (EPH) 1. EPH is characterized by a mPAP/CO-slope > 3 mmHg/L/min during exercise testing. In the classification of PH five groups are distinguished: Pulmonary arterial hypertension (group 1), PH associated with left heart disease (group 2), PH associated with lung diseases and/or hypoxia (Group 3), PH associated with pulmonary artery obstructions (group 4) and PH with unclear and/or multi-factorial mechanisms (group 5).In the following guideline-translation we focus on novel aspects regarding the definition and classification of PH and to provide additional background information.

Dark-Field Chest Radiography Outperforms Conventional Chest Radiography for the Diagnosis and Staging of Pulmonary Emphysema.

OBJECTIVES: Dark-field chest radiography (dfCXR) has recently reached clinical trials. Here we compare dfCXR to conventional radiography for the detection and staging of pulmonary emphysema. MATERIALS AND METHODS: Subjects were included after a medically indicated computed tomography (CT) scan, showing either no lung impairments or different stages of emphysema. To establish a ground truth, all CT scans were assessed by 3 radiologists assigning emphysema severity scores based on the Fleischner Society classification scheme.Participants were imaged at a commercial chest radiography device and at a prototype for dfCXR, yielding both attenuation-based and dark-field images. Three radiologists blinded to CT score independently assessed images from both devices for presence and severity of emphysema (no, mild, moderate, severe).Statistical analysis included evaluation of receiver operating characteristic curves and pairwise comparison of adjacent Fleischner groups using an area under the curve (AUC)-based z test with a significance level of 0.05. RESULTS: A total of 88 participants (54 men) with a mean age of 64 ± 12 years were included. Compared with conventional images (AUC = 0.73), readers were better able to identify emphysema with images from the dark-field prototype (AUC = 0.85, P = 0.005). Although ratings of adjacent emphysema severity groups with conventional radiographs differed only for trace and mild emphysema, ratings based on images from the dark-field prototype were different for trace and mild, mild and moderate, and moderate and confluent emphysema. CONCLUSIONS: Dark-field chest radiography is superior to conventional chest radiography for emphysema diagnosis and staging, indicating the technique's potential as a low-dose diagnostic tool for emphysema assessment.

Advanced Phase-Retrieval for Stepping-Free X-Ray Dark-Field Computed Tomography.

Grating-based phase- and dark-field-contrast X-ray imaging is a novel technology that aims to extend conventional attenuation-based X-ray imaging by unlocking two additional contrast modalities. The so called phase-contrast and dark-field channels provide enhanced soft tissue contrast and additional microstructural information. Accessing this additional information comes at the expense of a more intricate measurement setup and necessitates sophisticated data processing. A big challenge for translating grating-based dark-field computed tomography to medical applications lies in minimizing the data acquisition time. While a continuously moving detector is ideal, it prohibits conventional phase stepping techniques that require multiple projections under the same angle with different grating positions. One solution to this problem is the so-called sliding window processing approach that is compatible with continuous data acquisition. However, conventional sliding window techniques lead to crosstalk-artifacts between the three image channels, if the projection of the sample moves too fast on the detector within a processing window. In this work we introduce a new interpretation of the phase retrieval problem for continuous acquisitions as a demodulation problem. In this interpretation, we identify the origin of the crosstalk-artifacts as partially overlapping modulation side bands. Furthermore, we present three algorithmic extensions that improve the conventional sliding-window-based phase retrieval and mitigate crosstalk-artifacts. The presented algorithms are tested in a simulation study and on experimental data from a human-scale dark-field CT prototype. In both cases they achieve a substantial reduction of the occurring crosstalk-artifacts.

X-ray dark-field chest radiography: a reader study to evaluate the diagnostic quality of attenuation chest X-rays from a dual-contrast scanning prototype.

OBJECTIVES: To compare the visibility of anatomical structures and overall quality of the attenuation images obtained with a dark-field X-ray radiography prototype with those from a commercial radiography system. METHODS: Each of the 65 patients recruited for this study obtained a thorax radiograph at the prototype and a reference radiograph at the commercial system. Five radiologists independently assessed the visibility of anatomical structures, the level of motion artifacts, and the overall image quality of all attenuation images on a five-point scale, with 5 points being the highest rating. The average scores were compared between the two image types. The differences were evaluated using an area under the curve (AUC) based z-test with a significance level of p ≤ 0.05. To assess the variability among the images, the distributions of the average scores per image were compared between the systems. RESULTS: The overall image quality was rated high for both devices, 4.2 for the prototype and 4.6 for the commercial system. The rating scores varied only slightly between both image types, especially for structures relevant to lung assessment, where the images from the commercial system were graded slightly higher. The differences were statistically significant for all criteria except for the bronchial structures, the cardiophrenic recess, and the carina. CONCLUSIONS: The attenuation images acquired with the prototype were assigned a high diagnostic quality despite a lower resolution and the presence of motion artifacts. Thus, the attenuation-based radiographs from the prototype can be used for diagnosis, eliminating the need for an additional conventional radiograph. KEY POINTS: • Despite a low tube voltage (70 kVp) and comparably long acquisition time, the attenuation images from the dark-field chest radiography system achieved diagnostic quality for lung assessment. • Commercial chest radiographs obtained a mean rating score regarding their diagnostic quality of 4.6 out of 5, and the grating-based images had a slightly lower mean rating score of 4.2 out of 5. • The difference in rating scores for anatomical structures relevant to lung assessment is below 5%.

Modeling Vibrations of a Tiled Talbot-Lau Interferometer on a Clinical CT.

X-ray computed tomography (CT) is an invaluable imaging technique for non-invasive medical diagnosis. However, for soft tissue in the human body the difference in attenuation is inherently small. Grating-based X-ray phase-contrast is a relatively novel imaging method which detects additional interaction mechanisms between photons and matter, namely refraction and small-angle scattering, to generate additional images with different contrast. The experimental setup involves a Talbot-Lau interferometer whose susceptibility to mechanical vibrations hindered acquisition schemes suitable for clinical routine in the past. We present a processing pipeline to identify spatially and temporally variable fluctuations occurring in an interferometer installed on a continuously rotating clinical CT gantry. The correlations of the vibrations in the modular grating setup are exploited to identify a small number of relevant fluctuation modes, allowing for a sample reconstruction free of vibration artifacts.

Initial Characterization of Dark-Field CT on a Clinical Gantry.

X-ray computed tomography (CT) is an important non-destructive imaging technique, particularly in clinical diagnostics. Even with the latest innovations like dual-energy and photon-counting CT, the image contrast is solely generated from attenuation in the tissue. An extension - fully compatible with these novelties - is dark-field CT, which retrieves an additional, so-called dark-field contrast. Unlike the attenuation channel, the dark-field channel is sensitive to tissue microstructure and porosity below the resolution of the imaging system, which allows additional insights into the health of the lung tissue or the structure of calcifications. The potential clinical value has been demonstrated in several preclinical studies and recently also in radiography patient studies. Just recently the first dark-field CT for the human body was established at the Technical University of Munich and in this paper, we discuss the performance of this prototype. We evaluate the interferometer components and the imposed challenges that the integration into the CT gantry brings by comparing the results to simulations and measurements at a laboratory setup. The influence of the clinical X-ray source on the Talbot-Lau interferometer and the impact of vibrations, which are immanent on the clinical CT gantry, are analyzed in detail to reveal their characteristic frequencies and origin. A beam hardening correction is introduced as an important step to adapt to the poly-chromatic spectrum and make quantitative dark-field imaging possible. We close with an analysis of the image resolution and the applied patient dose, and conclude that the performance is sufficient to suggest initial patient studies using the presented dark-field CT system.

Technical Design Considerations of a Human-Scale Talbot-Lau Interferometer for Dark-Field CT.

Computed tomography (CT) as an important clinical diagnostics method can profit from extension with dark-field imaging, as it is currently restricted to X-rays' attenuation contrast only. Dark-field imaging allows access to more tissue properties, such as micro-structural texture or porosity. The up-scaling process to clinical scale is complex because several design constraints must be considered. The two most important ones are that the finest grating is limited by current manufacturing technology to a [Formula: see text] period and that the interferometer should fit into the CT gantry with minimal modifications only. In this work we discuss why an inverse interferometer and a triangular G1 profile are advantageous and make a compact and sensitive interferometer implementation feasible. Our evaluation of the triangular grating profile reveals a deviation in the interference pattern compared to standard grating profiles, which must be considered in the subsequent data processing. An analysis of the grating orientation demonstrates that currently only a vertical layout can be combined with cylindrical bending of the gratings. We also provide an in-depth discussion, including a new simulation approach, of the impact of the extended X-ray source spot which can lead to large performance loss and present supporting experimental results. This analysis reveals a vastly increased sensitivity to geometry and grating period deviations, which must be considered early in the system design process.

Dark-field chest X-ray imaging for the assessment of COVID-19-pneumonia.

BACKGROUND: Currently, alternative medical imaging methods for the assessment of pulmonary involvement in patients infected with COVID-19 are sought that combine a higher sensitivity than conventional (attenuation-based) chest radiography with a lower radiation dose than CT imaging. METHODS: Sixty patients with COVID-19-associated lung changes in a CT scan and 40 subjects without pathologic lung changes visible in the CT scan were included (in total, 100, 59 male, mean age 58 ± 14 years). All patients gave written informed consent. We employed a clinical setup for grating-based dark-field chest radiography, obtaining both a dark-field and a conventional attenuation image in one image acquisition. Attenuation images alone, dark-field images alone, and both displayed simultaneously were assessed for the presence of COVID-19-associated lung changes on a scale from 1 to 6 (1 = surely not, 6 = surely) by four blinded radiologists. Statistical analysis was performed by evaluation of the area under the receiver-operator-characteristics curves (AUC) using Obuchowski's method with a 0.05 level of significance. RESULTS: We show that dark-field imaging has a higher sensitivity for COVID-19-pneumonia than attenuation-based imaging and that the combination of both is superior to one imaging modality alone. Furthermore, a quantitative image analysis shows a significant reduction of dark-field signals for COVID-19-patients. CONCLUSIONS: Dark-field imaging complements and improves conventional radiography for the visualisation and detection of COVID-19-pneumonia.

Computed tomography (CT) imaging uses X-rays to obtain images of the inside of the body. It is used to look at lung damage in patients with COVID-19. However, CT imaging exposes the patient to a considerable amount of radiation. As radiation exposure can lead to the development of cancer, exposure should be minimised. Conventional plain X-ray imaging uses lower amounts of radiation but lacks sensitivity. We used dark-field chest X-ray imaging, which also uses low amounts of radiation, to assess the lungs of patients with COVID-19. Radiologists identified pneumonia in patients more easily from dark-field images than from usual plain X-ray images. We anticipate dark-field X-ray imaging will be useful to follow-up patients suspected of having lung damage.

Kinetic Regulation of the Mammalian Sterile 20-like Kinase 2 (MST2).

Canonically, MST1/2 functions as a core kinase of the Hippo pathway and noncanonically during both apoptotic signaling and with RASSFs in T-cells. Faithful signal transduction by MST1/2 relies on both appropriate activation and regulated substrate phosphorylation by the activated kinase. Considerable progress has been made in understanding the molecular mechanisms regulating the activation of MST1/2 and identifying downstream signaling events. Here, we investigated the ability of MST2 to phosphorylate a peptide substrate and how that activity is regulated. Using a steady-state kinetic system, we parse the contribution of different factors to substrate phosphorylation, including the domains of MST2, phosphorylation, caspase cleavage, and complex formation. We found that in the unphosphorylated state, the SARAH domain stabilizes interactions with a peptide substrate and promotes turnover. Phosphorylation drives the activity of MST2, and once activated, MST2 is not further regulated by complex formation with other Hippo pathway components (SAV1, MOB1A, and RASSF5). We also show that the phosphorylated, caspase-cleaved MST2 is as active as the full-length one, suggesting that caspase-stimulated activity arises through noncatalytic mechanisms. The kinetic analysis presented here establishes a framework for interpreting how signaling events and post-translational modifications contribute to the signaling of MST2 in vivo.

Dark-field chest x-ray imaging: first experience in patients with alpha1-antitrypsin deficiency.

BACKGROUND: Spirometry and conventional chest x-ray have limitations in investigating early emphysema, while computed tomography, the reference imaging method in this context, is not part of routine patient care due to its higher radiation dose. In this work, we investigated a novel low-dose imaging modality, dark-field chest x-ray, for the evaluation of emphysema in patients with alpha1-antitrypsin deficiency. METHODS: By exploiting wave properties of x-rays for contrast formation, dark-field chest x-ray visualises the structural integrity of the alveoli, represented by a high signal over the lungs in the dark-field image. We investigated four patients with alpha1-antitrypsin deficiency with a novel dark-field x-ray prototype and simultaneous conventional chest x-ray. The extent of pulmonary function impairment was assessed by pulmonary function measurement and regional emphysema distribution was compared with CT in one patient. RESULTS: We show that dark-field chest x-ray visualises the extent of pulmonary emphysema displaying severity and regional differences. Areas with low dark-field signal correlate with emphysematous changes detected by computed tomography using a threshold of -950 Hounsfield units. The airway parameters obtained by whole-body plethysmography and single breath diffusing capacity of the lungs for carbon monoxide demonstrated typical changes of advanced emphysema. CONCLUSIONS: Dark-field chest x-ray directly visualised the severity and regional distribution of pulmonary emphysema compared to conventional chest x-ray in patients with alpha1-antitrypsin deficiency. Due to the ultra-low radiation dose in comparison to computed tomography, dark-field chest x-ray could be beneficial for long-term follow-up in these patients.

Dark-field computed tomography reaches the human scale.

X-ray computed tomography (CT) is one of the most commonly used three-dimensional medical imaging modalities today. It has been refined over several decades, with the most recent innovations including dual-energy and spectral photon-counting technologies. Nevertheless, it has been discovered that wave-optical contrast mechanisms-beyond the presently used X-ray attenuation-offer the potential of complementary information, particularly on otherwise unresolved tissue microstructure. One such approach is dark-field imaging, which has recently been introduced and already demonstrated significantly improved radiological benefit in small-animal models, especially for lung diseases. Until now, however, dark-field CT could not yet be translated to the human scale and has been restricted to benchtop and small-animal systems, with scan durations of several minutes or more. This is mainly because the adaption and upscaling to the mechanical complexity, speed, and size of a human CT scanner so far remained an unsolved challenge. Here, we now report the successful integration of a Talbot-Lau interferometer into a clinical CT gantry and present dark-field CT results of a human-sized anthropomorphic body phantom, reconstructed from a single rotation scan performed in 1 s. Moreover, we present our key hardware and software solutions to the previously unsolved roadblocks, which so far have kept dark-field CT from being translated from the optical bench into a rapidly rotating CT gantry, with all its associated challenges like vibrations, continuous rotation, and large field of view. This development enables clinical dark-field CT studies with human patients in the near future.

Qualitative and Quantitative Assessment of Emphysema Using Dark-Field Chest Radiography.

Background Dark-field chest radiography allows for assessment of lung alveolar structure by exploiting wave optical properties of x-rays. Purpose To evaluate the qualitative and quantitative features of dark-field chest radiography in participants with pulmonary emphysema as compared with those in healthy control subjects. Materials and Methods In this prospective study conducted from October 2018 to October 2020, participants aged at least 18 years who underwent clinically indicated chest CT were screened for participation. Inclusion criteria were an ability to consent to the procedure and stand upright without help. Exclusion criteria were pregnancy, serious medical conditions, and any lung condition besides emphysema that was visible on CT images. Participants were examined with a clinical dark-field chest radiography prototype that simultaneously acquired both attenuation-based radiographs and dark-field chest radiographs. Dark-field coefficients were tested for correlation with each participant's CT-based emphysema index using the Spearman correlation test. Dark-field coefficients of adjacent groups in the semiquantitative Fleischner Society emphysema grading system were compared using a Wilcoxon Mann-Whitney U test. The capability of the dark-field coefficient to enable detection of emphysema was evaluated with receiver operating characteristics curve analysis. Results A total of 83 participants (mean age, 65 years ± 12 [standard deviation]; 52 men) were studied. When compared with images from healthy participants, dark-field chest radiographs in participants with emphysema had a lower and inhomogeneous dark-field signal intensity. The locations of focal signal intensity loss on dark-field images corresponded well with emphysematous areas found on CT images. The dark-field coefficient was negatively correlated with the quantitative CT-based emphysema index (r = -0.54, P < .001). Participants with Fleischner Society grades of mild, moderate, confluent, or advanced destructive emphysema exhibited a lower dark-field coefficient than those without emphysema (eg, 1.3 m-1 ± 0.6 for participants with confluent or advanced destructive emphysema vs 2.6 m-1 ± 0.4 for participants without emphysema; P < .001). The area under the receiver operating characteristic curve for detection of mild emphysema was 0.79. Conclusion Pulmonary emphysema leads to reduced signal intensity on dark-field chest radiographs, showing the technique has potential as a diagnostic tool in the assessment of lung diseases. © RSNA, 2022 See also the editorial by Hatabu and Madore in this issue.

Generational Differences in Nurses' Intention to Leave.

There are many studies about nurses' intention to leave their jobs and contributing factors. However, there is a lack of research about generational differences in nurses' intention to leave. This evidence may help with workforce planning and targeting specific generations of nurses with retention interventions. Using the National Database of Nursing Quality Indicators 2018 Annual Registered Nurse Survey, we used descriptive statistics and multivariate logistic regression to examine the prevalence of and reasons for nurses' intention to leave in the next year by generational age group. Our sample included 207,636 hospital nurses from across the United States. We found that 21% of nurses (n = 44,082) reported intention to leave. When comparing generations, there were differences in intention to leave, as well as differences in potentially preventable, career advancement, and personal intention to leave reasons. Workload/staffing was a common reason across generations, indicating that certain interventions may be applicable regardless of generation.