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.

Comparing x-ray phase-contrast imaging using a Talbot array illuminator to propagation-based imaging for non-homogeneous biomedical samples.

Phase-contrast computed tomography can visualize soft tissue samples with high contrast. At coherent sources, propagation-based imaging (PBI) techniques are among the most common, as they are easy to implement and produce high-resolution images. Their downside is a low degree of quantitative data due to simplifying assumptions of the sample properties in the reconstruction. These assumptions can be avoided, by using quantitative phase-contrast techniques as an alternative. However, these often compromise spatial resolution and require complicated setups. In order to overcome this limitation, we designed and constructed a new imaging setup using a 2D Talbot array illuminator as a wavefront marker and speckle-based imaging phase-retrieval techniques. We developed a post-processing chain that can compensate for wavefront marker drifts and that improves the overall sensitivity. By comparing two measurements of biomedical samples, we demonstrate that the spatial resolution of our setup is comparable to the one of PBI scans while being able to successfully image a sample that breaks the typical homogeneity assumption used in PBI.

Fabrication of X-ray absorption gratings by centrifugal deposition of bimodal tungsten particles in high aspect ratio silicon templates.

Grating-based X-ray imaging employs high aspect ratio absorption gratings to generate contrast induced by attenuating, phase-shifting, and small-angle scattering properties of the imaged object. The fabrication of the absorption gratings remains a crucial challenge of the method on its pathway to clinical applications. We explore a simple and fast centrifugal tungsten particle deposition process into silicon-etched grating templates, which has decisive advantages over conventional methods. For that, we use a bimodal tungsten particle suspension which is introduced into a custom designed grating holder and centrifuged at over 1000×g. Gratings with 45 µm period, 450 µm depth, and 170 mm × 38 mm active area are successfully processed reaching a homogeneous absorber filling. The effective absorbing tungsten thickness in the trenches is 207 µm resulting in a filling ratio of 46.6% compared to a voidless filling. The grating was tested in a Talbot-Lau interferometer designed for clinical X-ray dark-field computed tomography, where visibilities up to 33.6% at 60 kV were achieved.

Retrieval of 3D information in X-ray dark-field imaging with a large field of view.

X-ray dark-field imaging is a widely researched imaging technique, with many studies on samples of very different dimensions and at very different resolutions. However, retrieval of three-dimensional (3D) information for human thorax sized objects has not yet been demonstrated. We present a method, similar to classic tomography and tomosynthesis, to obtain 3D information in X-ray dark-field imaging. Here, the sample is moved through the divergent beam of a Talbot-Lau interferometer. Projections of features at different distances from the source seemingly move with different velocities over the detector, due to the cone beam geometry. The reconstruction of different focal planes exploits this effect. We imaged a chest phantom and were able to locate different features in the sample (e.g. the ribs, and two sample vials filled with water and air and placed in the phantom) to corresponding focal planes. Furthermore, we found that image quality and detectability of features is sufficient for image reconstruction with a dose of 68 µSv at an effective pixel size of [Formula: see text]. Therefore, we successfully demonstrated that the presented method is able to retrieve 3D information in X-ray dark-field imaging.

Signal Retrieval from Non-Sinusoidal Intensity Modulations in X-ray and Neutron Interferometry Using Piecewise-Defined Polynomial Function.

Grating-based phase-contrast and dark-field imaging systems create intensity modulations that are usually modeled with sinusoidal functions to extract transmission, differential-phase shift, and scatter information. Under certain system-related conditions, the modulations become non-sinusoidal and cause artifacts in conventional processing. To account for that, we introduce a piecewise-defined periodic polynomial function that resembles the physical signal formation process, modeling convolutions of binary periodic functions. Additionally, we extend the model with an iterative expectation-maximization algorithm that can account for imprecise grating positions during phase-stepping. We show that this approach can process a higher variety of simulated and experimentally acquired data, avoiding most artifacts.

X-ray dark-field chest imaging for detection and quantification of emphysema in patients with chronic obstructive pulmonary disease: a diagnostic accuracy study.

BACKGROUND: Although advanced medical imaging technologies give detailed diagnostic information, a low-dose, fast, and inexpensive option for early detection of respiratory diseases and follow-ups is still lacking. The novel method of x-ray dark-field chest imaging might fill this gap but has not yet been studied in living humans. Enabling the assessment of microstructural changes in lung parenchyma, this technique presents a more sensitive alternative to conventional chest x-rays, and yet requires only a fraction of the dose applied in CT. We studied the application of this technique to assess pulmonary emphysema in patients with chronic obstructive pulmonary disease (COPD). METHODS: In this diagnostic accuracy study, we designed and built a novel dark-field chest x-ray system (Technical University of Munich, Munich, Germany)-which is also capable of simultaneously acquiring a conventional thorax radiograph (7 s, 0·035 mSv effective dose). Patients who had undergone a medically indicated chest CT were recruited from the department of Radiology and Pneumology of our site (Klinikum rechts der Isar, Technical University of Munich, Munich, Germany). Patients with pulmonary pathologies, or conditions other than COPD, that might influence lung parenchyma were excluded. For patients with different disease stages of pulmonary emphysema, x-ray dark-field images and CT images were acquired and visually assessed by five readers. Pulmonary function tests (spirometry and body plethysmography) were performed for every patient and for a subgroup of patients the measurement of diffusion capacity was performed. Individual patient datasets were statistically evaluated using correlation testing, rank-based analysis of variance, and pair-wise post-hoc comparison. FINDINGS: Between October, 2018 and December, 2019 we enrolled 77 patients. Compared with CT-based parameters (quantitative emphysema ρ=-0·27, p=0·089 and visual emphysema ρ=-0·45, p=0·0028), the dark-field signal (ρ=0·62, p<0·0001) yields a stronger correlation with lung diffusion capacity in the evaluated cohort. Emphysema assessment based on dark-field chest x-ray features yields consistent conclusions with findings from visual CT image interpretation and shows improved diagnostic performance than conventional clinical tests characterising emphysema. Pair-wise comparison of corresponding test parameters between adjacent visual emphysema severity groups (CT-based, reference standard) showed higher effect sizes. The mean effect size over the group comparisons (absent-trace, trace-mild, mild-moderate, and moderate-confluent or advanced destructive visual emphysema grades) for the COPD assessment test score is 0·21, for forced expiratory volume in 1 s (FEV1)/functional vital capacity is 0·25, for FEV1% of predicted is 0·23, for residual volume % of predicted is 0·24, for CT emphysema index is 0·35, for dark-field signal homogeneity within lungs is 0·38, for dark-field signal texture within lungs is 0·38, and for dark-field-based emphysema severity is 0·42. INTERPRETATION: X-ray dark-field chest imaging allows the diagnosis of pulmonary emphysema in patients with COPD because this technique provides relevant information representing the structural condition of lung parenchyma. This technique might offer a low radiation dose alternative to CT in COPD and potentially other lung disorders. FUNDING: European Research Council, Deutsche Forschungsgemeinschaft, Royal Philips, and Karlsruhe Nano Micro Facility.

Whole-body x-ray dark-field radiography of a human cadaver.

BACKGROUND: Grating-based x-ray dark-field and phase-contrast imaging allow extracting information about refraction and small-angle scatter, beyond conventional attenuation. A step towards clinical translation has recently been achieved, allowing further investigation on humans. METHODS: After the ethics committee approval, we scanned the full body of a human cadaver in anterior-posterior orientation. Six measurements were stitched together to form the whole-body image. All radiographs were taken at a three-grating large-object x-ray dark-field scanner, each lasting about 40 s. Signal intensities of different anatomical regions were assessed. The magnitude of visibility reduction caused by beam hardening instead of small-angle scatter was analysed using different phantom materials. Maximal effective dose was 0.3 mSv for the abdomen. RESULTS: Combined attenuation and dark-field radiography are technically possible throughout a whole human body. High signal levels were found in several bony structures, foreign materials, and the lung. Signal levels were 0.25 ± 0.13 (mean ± standard deviation) for the lungs, 0.08 ± 0.06 for the bones, 0.023 ± 0.019 for soft tissue, and 0.30 ± 0.02 for an antibiotic bead chain. We found that phantom materials, which do not produce small-angle scatter, can generate a strong visibility reduction signal. CONCLUSION: We acquired a whole-body x-ray dark-field radiograph of a human body in few minutes with an effective dose in a clinical acceptable range. Our findings suggest that the observed visibility reduction in the bone and metal is dominated by beam hardening and that the true dark-field signal in the lung is therefore much higher than that of the bone.

High-resolution and sensitivity bi-directional x-ray phase contrast imaging using 2D Talbot array illuminators.

Two-dimensional (2D) Talbot array illuminators (TAIs) were designed, fabricated, and evaluated for high-resolution high-contrast x-ray phase imaging of soft tissue at 10-20 keV. The TAIs create intensity modulations with a high compression ratio on the micrometer scale at short propagation distances. Their performance was compared with various other wavefront markers in terms of period, visibility, flux efficiency, and flexibility to be adapted for limited beam coherence and detector resolution. Differential x-ray phase contrast and dark-field imaging were demonstrated with a one-dimensional, linear phase stepping approach yielding 2D phase sensitivity using unified modulated pattern analysis (UMPA) for phase retrieval. The method was employed for x-ray phase computed tomography reaching a resolution of 3 µm on an unstained murine artery. It opens new possibilities for three-dimensional, non-destructive, and quantitative imaging of soft matter such as virtual histology. The phase modulators can also be used for various other x-ray applications such as dynamic phase imaging, super-resolution structured illumination microscopy, or wavefront sensing.

X-ray Dark-Field Radiography: Potential for Visualization of Monosodium Urate Deposition.

OBJECTIVE: The aim of this study was to evaluate the potential of x-ray dark-field radiography for the noninvasive detection of monosodium urate (MSU) crystals as a novel diagnostic tool for gout. MATERIALS AND METHODS: Contrast-to-noise ratios of MSU crystals in conventional radiography and dark-field radiography have been compared in a proof of principle measurement. Monosodium urate crystals have been injected into mouse legs in an ex vivo experimental gout setup. Three radiologists independently evaluated the images for the occurrence of crystal deposits in a blinded study for attenuation images only, dark-field images only, and with both images available for a comprehensive diagnosis. All imaging experiments have been performed at an experimental x-ray dark-field setup with a 3-grating interferometer, a rotating anode tube (50 kVp), and a photon-counting detector (effective pixel size, 166 µm). RESULTS: X-ray dark-field radiography provided a strong signal increase for MSU crystals in a physiological buffer solution compared with conventional attenuation radiography with a contrast-to-noise ratio increase from 0.8 to 19.3. Based on conventional attenuation images only, the reader study revealed insufficient diagnostic performance (sensitivity, 11%; specificity, 92%) with poor interrater agreement (Cohen's coefficient κ = 0.031). Based on dark-field images, the sensitivity increased to 100%, specificity remained at 92%, and the interrater agreement increased to κ = 0.904. Combined diagnosis based on both image modalities maximized both sensitivity and specificity to 100% with absolute interrater agreement (κ = 1.000). CONCLUSIONS: X-ray dark-field radiography enables the detection of MSU crystals in a mouse-based gout model. The simultaneous avaliability of a conventional attenuation image together with the dark-field image provides excellent detection rates of gout deposits with high specificity.

A high visibility Talbot-Lau neutron grating interferometer to investigate stress-induced magnetic degradation in electrical steel.

Neutron grating interferometry (nGI) is a unique technique allowing to probe magnetic and nuclear properties of materials not accessible in standard neutron imaging. The signal-to-noise ratio of an nGI setup is strongly dependent on the achievable visibility. Hence, for analysis of weak signals or short measurement times a high visibility is desired. We developed a new Talbot-Lau interferometer using the third Talbot order with an unprecedented visibility (0.74) over a large field of view. Using the third Talbot order and the resulting decreased asymmetry allows to access a wide correlation length range. Moreover, we have used a novel technique for the production of the absorption gratings which provides nearly binary gratings even for thermal neutrons. The performance of the new interferometer is demonstrated by visualizing the local magnetic domain wall density in electrical steel sheets when influenced by residual stress induced by embossing. We demonstrate that it is possible to affect the density of the magnetic domain walls by embossing and therefore to engineer the guiding of magnetic fields in electrical steel sheets. The excellent performance of our new setup will also facilitate future studies of dynamic effects in electric steels and other systems.

Comparison of Thermal Neutron and Hard X-ray Dark-Field Tomography.

High visibility (0.56) neutron-based multi-modal imaging with a Talbot-Lau interferometer at a wavelength of 1.6 Å is reported. A tomography scan of a strongly absorbing quartz geode sample was performed with both the neutron and an X-ray grating interferometer (70 kVp) for a quantitative comparison. Small scattering structures embedded in the absorbing silica matrix were well resolved in neutron dark-field CT slices with a spatial resolution of about 300 µm. Beneficial effects, such as monochromaticity and stronger penetration power of the used neutron radiation, helped to avoid the beam hardening-related artificial dark-field signal which was present in the X-ray data. Both dark-field modalities show mostly the same structures; however, some scattering features appear only in the neutron domain. Potential applications of combined X-ray and neutron multi-modal CT enabling one to probe both the nuclear and the electron density-related structural properties are discussed. strongly absorbing samples are now accessible for the dark-field modality by the use of thermal neutrons.

Quality and parameter control of X-ray absorption gratings by angular X-ray transmission.

Here we report on a non-destructive, spatially resolving and easy to implement quality and parameter control method for high aspect ratio X-ray absorption gratings. Based on angular X-ray transmission measurements, our proposed technique allows to determine the duty cycle, the transmittance, the height, as well as the local inclination of the absorbing grating structures. A key advantage of the presented method is a fast and extensive grating quality evaluation without the need of implementing an entire grating interferometer. In addition to the local and surface-based analysis using a scanning electron microscope, our non-destructive method provides global averaged macroscopic and spatially resolved grating structure information without the requirement of resolving individual grating lines.

Metric-guided regularisation parameter selection for statistical iterative reconstruction in computed tomography.

As iterative reconstruction in Computed Tomography (CT) is an ill-posed problem, additional prior information has to be used to get a physically meaningful result (close to ground truth if available). However, the amount of influence of the regularisation prior is crucial to the outcome of the reconstruction. Therefore, we propose a scheme for tuning the strength of the prior via a certain image metric. In this work, the parameter is tuned for minimal histogram entropy in selected regions of the reconstruction as histogram entropy is a very basic approach to characterise the information content of data. We performed a sweep over different regularisation parameters showing that the histogram entropy is a suitable metric as it is well behaved over a wide range of parameters. The parameter determination is a feedback loop approach we applied to numerically simulated FORBILD phantom data and verified with an experimental measurement of a micro-CT device. The outcome is evaluated visually and quantitatively by means of root mean squared error (RMSE) and structural similarity (SSIM) for the simulation and visually for the measured sample (no ground truth available). The final reconstructed images exhibit noise-suppressed iterative reconstruction. For both datasets, the optimisation is robust where its initial value is concerned. The parameter tuning approach shows that the proposed metric-driven feedback loop is a promising tool for finding a suitable regularisation parameter in statistical iterative reconstruction.