Dark-field Signal Research Articles

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

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

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.

Statistical optics modeling of dark-field scattering in X-ray grating interferometers: Part 2. Simulation

A grating-based Talbot-Lau X-ray interferometer provides three imaging modalities, namely attenuation, differential phase contrast, and dark field. Of these, dark-field imaging is uniquely capable of detecting and characterizing micron-scale fine structure in an object via small-angle scattering that reduces fringe visibility. In Part 1 [Opt. Express 29, 40891 (2021)10.1364/OE.447794], we formulate a statistical optics model that predicts the change in visibility, or dark-field signal, as a function of the statistical properties of the scattering object as well as its location within the interferometer. In Part 2, we demonstrate use of this model by simulating an object comprising a random collection of scattering microspheres placed in an X-ray grating interferometer designed to operate at 28 keV. The statistical optics results are validated by numerical Fourier optics simulations.

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

SummaryBackgroundAlthough 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).MethodsIn 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.FindingsBetween 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.InterpretationX-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.FundingEuropean Research Council, Deutsche Forschungsgemeinschaft, Royal Philips, and Karlsruhe Nano Micro Facility.

X-ray dark field imaging: a tool for early diagnosis of emphysema in chronic obstructive pulmonary disease?

Grating-based x-ray dark-field imaging is a novel imaging modality that has been refined during the past decade for applications in biomedical imaging.1 This technique exploits the wave-like behaviour of x-rays to detect, quantify, and visualise small-angle x-ray scattering. The strength of the dark-field signal reflects the amount of small-angle x-ray scattering that cannot be detected with conventional x-ray devices. Small-angle x-ray scattering occurs at interfaces between structures of different electron density—eg, at air and tissue interfaces in the lung, making the lung an organ of special interest for x-ray dark-field imaging.

Simulation study towards quantitative X-ray and neutron tensor tomography regarding the validity of linear approximations of dark-field anisotropy

Tensor tomography is fundamentally based on the assumption of a both anisotropic and linear contrast mechanism. While the X-ray or neutron dark-field contrast obtained with Talbot(-Lau) interferometers features the required anisotropy, a preceding detailed study of dark-field signal origination however found its specific orientation dependence to be a non-linear function of the underlying anisotropic mass distribution and its orientation, especially challenging the common assumption that dark-field signals are describable by a function over the unit sphere. Here, two approximative linear tensor models with reduced orientation dependence are investigated in a simulation study with regard to their applicability to grating based X-ray or neutron dark-field tensor tomography. By systematically simulating and reconstructing a large sample of isolated volume elements covering the full range of feasible anisotropies and orientations, direct correspondences are drawn between the respective tensors characterizing the physically based dark-field model used for signal synthesization and the mathematically motivated simplified models used for reconstruction. The anisotropy of freely rotating volume elements is thereby confirmed to be, for practical reconstruction purposes, approximable both as a function of the optical axis’ orientation or as a function of the interferometer’s grating orientation. The eigenvalues of the surrogate models’ tensors are found to exhibit fuzzy, yet almost linear relations to those of the synthesization model. Dominant orientations are found to be recoverable with a margin of error on the order of magnitude of 1^{circ }. Although the input data must adequately address the full orientation dependence of dark-field anisotropy, the present results clearly support the general feasibility of quantitative X-ray dark-field tensor tomography within an inherent yet acceptable statistical margin of uncertainty.

Toward Compositional Contrast by Cryo-STEM.

Electron microscopy (EM) is the most versatile tool for the study of matter at scales ranging from subatomic to visible. The high vacuum environment and the charged irradiation require careful stabilization of many specimens of interest. Biological samples are particularly sensitive due to their composition of light elements suspended in an aqueous medium. Early investigators developed techniques of embedding and staining with heavy metal salts for contrast enhancement. Indeed, the Nobel Prize in 1974 recognized Claude, de Duve, and Palade for establishment of the field of cell biology, largely due to their developments in separation and preservation of cellular components for electron microscopy. A decade later, cryogenic fixation was introduced. Vitrification of the water avoids the need for dehydration and provides an ideal matrix in which the organic macromolecules are suspended; the specimen represents a native state, suddenly frozen in time at temperatures below -150 °C. The low temperature maintains a low vapor pressure for the electron microscope, and the amorphous nature of the medium avoids diffraction contrast from crystalline ice. Such samples are extremely delicate, however, and cryo-EM imaging is a race for information in the face of ongoing damage by electron irradiation. Through this journey, cryo-EM enhanced the resolution scale from membranes to molecules and most recently to atoms. Cryo-EM pioneers, Dubochet, Frank, and Henderson, were awarded the Nobel Prize in 2017 for high resolution structure determination of biological macromolecules.A relatively untapped feature of cryo-EM is its preservation of composition. Nothing is added and nothing removed. Analytical spectroscopies based on electron energy loss or X-ray emission can be applied, but the very small interaction cross sections conflict with the weak exposures required to preserve sample integrity. To what extent can we interpret quantitatively the pixel intensities in images themselves? Conventional cryo-transmission electron microscopy (TEM) is limited in this respect, due to the strong dependence of the contrast transfer on defocus and the absence of contrast at low spatial frequencies.Inspiration comes largely from a different modality for cryo-tomography, using soft X-rays. Contrast depends on the difference in atomic absorption between carbon and oxygen in a region of the spectrum between their core level ionization energies, the so-called water window. Three dimensional (3D) reconstruction provides a map of the local X-ray absorption coefficient. The quantitative contrast enables the visualization of organic materials without stain and measurement of their concentration quantitatively. We asked, what aspects of the quantitative contrast might be transferred to cryo-electron microscopy?Compositional contrast is accessible in scanning transmission EM (STEM) via incoherent elastic scattering, which is sensitive to the atomic number Z. STEM can be regarded as a high energy, low angle diffraction measurement performed pixel by pixel with a weakly convergent beam. When coherent diffraction effects are absent, that is, in amorphous materials, a dark field signal measures quantitatively the flux scattered from the specimen integrated over the detector area. Learning to interpret these signals will open a new dimension in cryo-EM. This Account describes our efforts so far to introduce STEM for cryo-EM and tomography of biological specimens. We conclude with some thoughts on further developments.

Quantitative analysis of speckle-based X-ray dark-field imaging using numerical wave-optics simulations

The dark-field signal measures the small-angle scattering strength and provides complementary diagnostic information. This is of particular interest for lung imaging due to the pronounced small-angle scatter from the alveolar microstructure. However, most dark-field imaging techniques are relatively complex, dose-inefficient, and require sophisticated optics and highly coherent X-ray sources. Speckle-based imaging promises to overcome these limitations due to its simple and versatile setup, only requiring the addition of a random phase modulator to conventional X-ray equipment. We investigated quantitatively the influence of sample structure, setup geometry, and source energy on the dark-field signal in speckle-based X-ray imaging with wave-optics simulations for ensembles of micro-spheres. We show that the dark-field signal is accurately predicted via a model originally derived for grating interferometry when using the mean frequency of the speckle pattern power spectral density as the characteristic speckle size. The size directly reflects the correlation length of the diffuser surface and did not change with energy or propagation distance within the near-field. The dark-field signal had a distinct dependence on sample structure and setup geometry but was also affected by beam hardening-induced modifications of the visibility spectrum. This study quantitatively demonstrates the behavior of the dark-field signal in speckle-based X-ray imaging.

Correlation of image quality parameters with tube voltage in X-ray dark-field chest radiography: a phantom study

Grating-based X-ray dark-field imaging is a novel imaging modality with enormous technical progress during the last years. It enables the detection of microstructure impairment as in the healthy lung a strong dark-field signal is present due to the high number of air-tissue interfaces. Using the experience from setups for animal imaging, first studies with a human cadaver could be performed recently. Subsequently, the first dark-field scanner for in-vivo chest imaging of humans was developed. In the current study, the optimal tube voltage for dark-field radiography of the thorax in this setup was examined using an anthropomorphic chest phantom. Tube voltages of 50–125 kVp were used while maintaining a constant dose-area-product. The resulting dark-field and attenuation radiographs were evaluated in a reader study as well as objectively in terms of contrast-to-noise ratio and signal strength. We found that the optimum tube voltage for dark-field imaging is 70 kVp as here the most favorable combination of image quality, signal strength, and sharpness is present. At this voltage, a high image quality was perceived in the reader study also for attenuation radiographs, which should be sufficient for routine imaging. The results of this study are fundamental for upcoming patient studies with living humans.

Label-Free Analyses of Minimal Residual Disease in ALL Using Deep Learning and Imaging Flow Cytometry

MD/MC and PR/JI contributed equallyMinimal residual disease is an important response biomarker for risk stratification in acute lymphoblastic leukaemia (ALL) and is assessed by two methodologies, molecular analyses of patient-specific, clonal antigen receptor rearrangements or flow cytometric analyses of aberrant leukaemia-associated immunophenotypes. Some clinical regimens use both methodologies and sequential samples of bone marrow and/or peripheral blood are assessed during, at the end of induction therapy and at time points beyond. Both MRD methods are highly specialised, laborious and for resource poor countries, are not affordable. In addition, a proportion of patients are not evaluable by either method.Technological advances in cytometry have led to imaging flow cytometers (IFC) which deliver all standard flow cytometric parameters, as well as a high quality image of each cell. We have previously shown that machine learning of IFC data can classify cell cycle phases within a cell, using only data from bright field (BF) and dark field (DF)1 and we hypothesised that this might be possible in the MRD setting. Thus, paired diagnostic and follow up bone marrow aspirates taken during remission induction from children with ALL (n=23, 6 at day 8 or day 15 or day 28 following the start of treatment) were stained with CD19 APC, CD10PE, CD34Texas Red, CD45APCH7 and DAPI and ran on an imaging flow cytometer (Amnis, Imagestream X Mark II) at x40 magnification. A standard sequential gating technique identified ALL cells and levels (range 90-0.01%) correlated with that assessed by traditional flow cytometry. Next, 200 morphological features were extracted from BF and DF images of cells including pixel intensities, size, shapes, textures and subcellular components and both supervised machine and deep learning algorithms were developed to correctly classify ALL cells in clinical samples. The classifiers were trained initially using all fluorescent and BF and DF parameters but then with a sequential leave-one-parameter-out. In parallel, iteration of the training-testing sets on 23 datasets, with a leave-one-sample-out approach was performed, to ensure prediction accuracy across samples. Correct cell classifiers peaked at 98.21% when all parameters were considered but even without antibody-conjugated signals, relying only in DAPI, DF and BF signals, correct cell classification averaged 85.36%. Finally, DF/BF in combination and BF alone still gave rise to correct cell call rates of 81.62% and 71.26% respectively.Thus, we report a new MRD detection method that is label free, using only the morphological features extracted from BF and DF cell images. The method is cheap, quick, and highly applicable and with a technology that could be simplified to be laser-free and allow point of care testing. Transferability of this unique methodological approach to other types of leukaemia is also feasible and may be further developed to give functional information e.g. cell cycle status.

Direct Differentiation of Pathological Changes in the Human Lung Parenchyma With Grating-Based Spectral X-ray Dark-Field Radiography.

Diagnostic lung imaging is often associated with high radiation dose and lacks sensitivity, especially for diagnosing early stages of structural lung diseases. Therefore, diagnostic imaging methods are required which provide sound diagnosis of lung diseases with a high sensitivity as well as low patient dose. In small animal experiments, the sensitivity of grating-based X-ray dark-field imaging to structural changes in the lung tissue was demonstrated. The energy-dependence of the X-ray dark-field signal of lung tissue is a function of its microstructure and not yet known. Furthermore, conventional X-ray dark-field imaging is not capable of differentiating different types of pathological changes, such as fibrosis and emphysema. Here we demonstrate the potential diagnostic power of grating-based X-ray dark-field in combination with spectral imaging in human chest radiography for the direct differentiation of lung diseases. We investigated the energy-dependent linear diffusion coefficient of simulated lung tissue with different diseases in wave-propagation simulations and validated the results with analytical calculations. Additionally, we modeled spectral X-ray dark-field chest radiography scans to exploit these differences in energy-dependency. The results demonstrate the potential to directly differentiate structural changes in the human lung. Consequently, grating-based spectral X-ray dark-field imaging potentially contributes to the differential diagnosis of structural lung diseases at a clinically relevant dose level.

Dual-Energy X-Ray Dark-Field Material Decomposition.

Dual-energy imaging is a clinically well-established technique that offers several advantages over conventional X-ray imaging. By performing measurements with two distinct X-ray spectra, differences in energy-dependent attenuation are exploited to obtain material-specific information. This information is used in various imaging applications to improve clinical diagnosis. In recent years, grating-based X-ray dark-field imaging has received increasing attention in the imaging community. The X-ray dark-field signal originates from ultra small-angle scattering within an object and thus provides information about the microstructure far below the spatial resolution of the imaging system. This property has led to a number of promising future imaging applications that are currently being investigated. However, different microstructures can hardly be distinguished with current X-ray dark-field imaging techniques, since the detected dark-field signal only represents the total amount of ultra small-angle scattering. To overcome these limitations, we present a novel concept called dual-energy X-ray dark-field material decomposition, which transfers the basic material decomposition approach from attenuation-based dual-energy imaging to the dark-field imaging modality. We develop a physical model and algorithms for dual-energy dark-field material decomposition and evaluate the proposed concept in experimental measurements. Our results suggest that by sampling the energy-dependent dark-field signal with two different X-ray spectra, a decomposition into two different microstructured materials is possible. Similar to dual-energy imaging, the additional microstructure-specific information could be useful for clinical diagnosis.

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

BackgroundGrating-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.MethodsAfter 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.ResultsCombined 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.ConclusionWe 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.

Suppression of artifacts in X-ray phase-contrast images retrieved by Fourier transform

Over the last two decades, the grating-based phase-contrast imaging has aroused the interest of a number of researchers. It could provide an access to three complementary signals simultaneously: the conventional absorption contrast, the differential phase contrast related to refraction of incident wave, and the dark-field contrast that relates to ultra small angle scattering in a sample. The grating-based phase-contrast signals have higher contrast sensitivity for some types of soft samples than the absorption signals. Dark-field signals have better diagnostic effects in the detection of lung tumors, pneumothorax and the identification of microcalcifications in breast. There are two main phase retrieval methods in grating-based X-ray phase-contrast imaging, i.e. phase stepping method and Fourier transform method. The phase signals retrieved by phase stepping is high precise and has low noise. But the sample suffers high dose due to at least three exposures. The phase signals retrieved by Fourier transform is low-dose due to the fact that only one image with sample is needed, but it is easily affected by artifacts when the size of the filtering window is too large. However, when the size of the filtering window is too small, the high-frequency information of the phase-contrast image will be lost, and the image will become blurred. A trade-off between definitions of the image and artifacts should be made. Since the phase-contrast signal and the dark-field signal of the sample are modulated by carrier fringes, the frequency spectrum of the detected image consists of many different harmonics. The artifacts in the retrieved signals originate from the spectrum aliasing between primary peak around zero spatial frequency and first-order harmonic peaks. Therefore, the subtraction between two images with phase difference can remove the primary peak, and the artifacts in the phase-contrast signals and dark-field signals will be suppressed. In order to further suppress the artifacts, we increase the frequency of carrier fringes, which results in a larger distance between first-order harmonic peaks in frequency domain. We finally attain artifact-free phase-contrast images and dark-field images while maintaining high definition of the images. The method proposed here is not only applicable to incoherent imaging system, but also to Talbot-Lau interferometer, and it would be useful in fast and low-dose X-ray phase-contrast and dark-field imaging.

X-Ray Dark-Field Chest Imaging Can Detect and Quantify Emphysema in COPD Patients

Background: Diseases of the respiratory system are leading global causes of chronic morbidity and mortality. While advanced medical imaging technologies of today deliver detailed diagnostic information, a low-dose, fast, and inexpensive option for early detection and/or follow-ups is still lacking. Here, we report on the first human application of a novel modality, namely X-ray dark-field chest imaging, which might fill this gap. 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 computed tomography (CT). Methods: For this first clinical evaluation, we have built a novel dark-field chest X-ray system, which is also capable of simultaneously acquiring a conventional thorax radiograph (7 seconds, 0·035 mSv effective dose). Representing a major medical condition, we selected chronic obstructive pulmonary disease as study subject to obtain a first impression of potential diagnostic benefits relevant to humans. For a collective of 77 patients with different disease stages, X-ray dark-field- and CT-images were acquired and visually assessed by 5 readers. In addition, pulmonary function tests were performed for every patient. The individual data sets were evaluated in a statistical work-up using correlation testing, rank-based analysis of variance, and pair-wise post-hoc comparison. Findings: Compared to CT-based parameters (quantitative emphysema: ρ=–0·27, p=0·0893 and visual emphysema: ρ=–0·45, p=0·0028), the dark-field signal (ρ=0·62, p<0·0001) yields a stronger correlation with diffusion capacity in the evaluated collective. 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 in comparison to conventional clinical tests characterizing emphysema. Interpretation: X-ray dark-field chest imaging allows the diagnosis of pulmonary emphysema as it provides relevant information representing the structural condition of lung parenchyma. Significant diagnostic benefits are also expected for other lung disorders. Funding Statement: We acknowledge financial support through the European Research Council, Royal Philips, Karlsruhe Nano Micro Facility. Declaration of Interests: T.K., A.Y., and T.P. are employees of Royal Philips. The remaining authors declare no competing interests. Ethics Approval Statement: The study was approved by the institutional ethics review board and the German Federal Office for Radiation Protection (Bundesamt fur Strahlenschutz, BfS) and the permission from authorities to operate the demonstrator system for first human applications was obtained. All participants gave written informed consent.

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 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 μ. 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.

Review and experimental verification of x-ray dark-field signal interpretations with respect to quantitative isotropic and anisotropic dark-field computed tomography

Talbot(-Lau) interferometric x-ray and neutron dark-field imaging has, over the past decade, gained substantial interest for its ability to provide insights into a sample’s microstructure below the imaging resolution by means of ultra small angle scattering effects. Quantitative interpretations of such images depend on models of the signal origination process that relate the observable image contrast to underlying physical processes. A review of such models is given here and their relation to the wave optical derivations by Yashiro et al and Lynch et al as well as to small angle scattering is discussed. Fresnel scaling is introduced to explain the characteristic distance dependence observed in cone beam geometries. Moreover, a model describing the anisotropic signals of fibrous objects is derived. The Yashiro-Lynch model is experimentally verified both in radiographic and tomographic imaging in a monochromatic synchrotron setting, considering both the effects of material and positional dependence of the resulting dark-field contrast. The effect of varying sample–detector distance on the dark-field signal is shown to be non-negligible for tomographic imaging, yet can be largely compensated for by symmetric acquisition trajectories. The derived orientation dependence of the dark-field contrast of fibrous materials both with respect to variations in autocorrelation width and scattering cross section is experimentally validated using carbon fiber reinforced rods.

Dark-field signal extraction in propagation-based phase-contrast imaging

A method for extracting the dark-field signal in propagation-based phase-contrast imaging is proposed. In the case of objects consisting predominantly of a single material, or several different materials with similar ratios of the real decrement to the imaginary part of the complex refractive index, the proposed method requires a single image for extraction of the dark-field signal in two-dimensional projection imaging. In the case of three-dimensional tomographic imaging, the method needs only one image to be collected at each projection angle. Initial examples using simulated and experimental data indicate that this method can improve visualization of small sharp features inside a larger object, e.g. the visualization of microcalcifications in propagation-based x-ray breast cancer imaging. It is suggested that the proposed approach may be useful in other forms of biomedical imaging, where it can help one to obtain additional small-angle scattering information without increasing the radiation dose to the sample.

Recent advances in X-ray imaging of breast tissue: From two- to three-dimensional imaging.

Breast cancer is a globally widespread disease whose detection has already been significantly improved by the introduction of screening programs. Nevertheless, mammography suffers from low soft tissue contrast and the superposition of diagnostically relevant anatomical structures as well as from low values for sensitivity and specificity especially for dense breast tissue. In recent years, two techniques for X-ray breast imaging have been developed that bring advances for the early detection of breast cancer. Grating-based phase-contrast mammography is a new imaging technique that is able to provide three image modalities simultaneously (absorption-contrast, phase-contrast and dark-field signal). Thus, an enhanced detection and delineation of cancerous structures in the phase-contrast image and an improved visualization and characterization of microcalcifications in the dark-field image is possible. Furthermore, latest studies about this approach show that dose-compatible imaging with polychromatic X-ray sources is feasible. In order to additionally overcome the limitations of projection-based imaging, efforts were also made towards the development of breast computed tomography (BCT), which recently led to the first clinical installation of an absorption-based BCT system. Further research combining the benefits of both imaging technologies is currently in progress. This review article summarizes the latest advances in phase-contrast imaging for the female breast (projection-based and three-dimensional view) with special focus on possible clinical implementations in the future.

A proof-of principal study using phase-contrast imaging for the detection of large airway pathologies after lung transplantation

In this study we aim to evaluate the assessment of bronchial pathologies in a murine model of lung transplantation with grating-based X-ray interferometry in vivo. Imaging was performed using a dedicated grating-based small-animal X-ray dark-field and phase-contrast scanner. While the contrast modality of the dark-field signal already showed several promising applications for diagnosing various types of pulmonary diseases, the phase-shifting contrast mechanism of the phase contrast has not yet been evaluated in vivo. For this purpose, qualitative analysis of phase-contrast images was performed and revealed pathologies due to previous lung transplantation, such as unilateral bronchial stenosis or bronchial truncation. Dependent lung parenchyma showed a strong loss in dark-field and absorption signal intensity, possibly caused by several post transplantational pathologies such as atelectasis, pleural effusion, or pulmonary infiltrates. With this study, we are able to show that bronchial pathologies can be visualized in vivo using conventional X-ray imaging when phase-contrast information is analysed. Absorption and dark-field images can be used to quantify the severity of lack of ventilation in the affected lung.