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.

[X-Ray Dark-field radiography: Does this carry potential for diagnosing gout in exotic pets?] / Die Dunkelfeld-Radiografie ­ ein neuer Weg zur Diagnostik von Gichterkrankungen bei Vögeln und Reptilien?

OBJECTIVE: The aim of this study is to evaluate whether X-ray dark-field (DF) radiography is useful for the diagnosis of gout in birds and reptiles and whether this preclinical model could be helpful to establish this non-invasive imaging method in human medicine. MATERIAL AND METHODS: A total of 18 limbs originating from 11 birds (7 different species) and 7 reptiles (4 different species) with and without suspected joint gout were measured using a grating-based X-ray dark-field setup and conventional X-ray examination, respectively. Each image acquisition generated a dark-field and a conventional absorption x-ray image. The results of the individual scans were compared with the results of a pathological examination and arthrocentesis. RESULTS: In 5 of the birds and 4 of the reptiles examined, gout was detected by pathologic examination. In each group, uric acid crystals were found in the joints of 3 animals by means of arthrocentesis. The uric acid crystals were detectable in 2 bird and 2 reptile limbs in the dark-field image. CONCLUSION: The study demonstrated that the urate crystals evoke a clearly visible dark field signal, whereas this was not the case in the conventional radiographs. CLINICAL RELEVANCE: The results obtained show that uric acid crystal detection using less invasive imaging methods in an animal model with birds and reptiles may expand gout diagnostics not only in veterinary medicine but also in human medicine and possibly replace arthrocentesis if a DF signal is detectable. Preclinical scanners which use X-ray dark-field and phase-contrast radiography already exist for hands and mammography.

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.

X-ray dark-field radiography for in situ gout diagnosis by means of an ex vivo animal study.

Gout is the most common form of inflammatory arthritis, caused by the deposition of monosodium urate (MSU) crystals in peripheral joints and tissue. Detection of MSU crystals is essential for definitive diagnosis, however the gold standard is an invasive process which is rarely utilized. In fact, most patients are diagnosed or even misdiagnosed based on manifested clinical signs, as indicated by the unchanged premature mortality among gout patients over the past decade, although effective treatment is now available. An alternative, non-invasive approach for the detection of MSU crystals is X-ray dark-field radiography. In our work, we demonstrate that dark-field X-ray radiography can detect naturally developed gout in animals with high diagnostic sensitivity and specificity based on the in situ measurement of MSU crystals. With the results of this study as a potential basis for further research, we believe that X-ray dark-field radiography has the potential to substantially improve gout diagnostics.

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.

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.

Grating-based spectral X-ray dark-field imaging for correlation with structural size measures.

X-ray dark-field (XDF) imaging accesses information on the small-angle scattering properties of the sample. With grating interferometry, the measured scattering signal is related to the sample's autocorrelation function, which was previously demonstrated for simple samples, such as mono-dispersed microspheres for which the autocorrelation function is mathematically given. However, in potential clinical applications of XDF imaging, complex microstructures, such as lung parenchyma are under investigation. Their bahaviour in XDF imaging is not yet known and no mathematical description of the autocorrelation function is derived so far. In this work we demonstrate the previously established correlation of the XDF data of complex sample structures with their autocorrelation function to be impractical. Furthermore, we propose an applicable correlation between XDF and the sample's structural parameter on the basis of mean chord length, a medically-approved measure for alveolar structure, known to be affected by structural lung diseases. Our findings reveal a correlation between energy-dependent XDF imaging and the sample's mean chord length. By that, a connection between a medical measure for alveoli and XDF is achieved, which is particularly important regarding potential future XDF lung imaging applications for the assessment of alveoli size in diagnostic lung imaging.

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.

Imaging features in post-mortem x-ray dark-field chest radiographs and correlation with conventional x-ray and CT.

BACKGROUND: Although x-ray dark-field imaging has been intensively investigated for lung imaging in different animal models, there is very limited data about imaging features in the human lungs. Therefore, in this work, a reader study on nine post-mortem human chest x-ray dark-field radiographs was performed to evaluate dark-field signal strength in the lungs, intraobserver and interobserver agreement, and image quality and to correlate with findings of conventional x-ray and CT. METHODS: In this prospective work, chest x-ray dark-field radiography with a tube voltage of 70 kVp was performed post-mortem on nine humans (3 females, 6 males, age range 52-88 years). Visual quantification of dark-field and transmission signals in the lungs was performed by three radiologists. Results were compared to findings on conventional x-rays and 256-slice computed tomography. Image quality was evaluated. For ordinal data, median, range, and dot plots with medians and 95% confidence intervals are presented; intraobserver and interobserver agreement were determined using weighted Cohen κ. RESULTS: Dark-field signal grading showed significant differences between upper and middle (p = 0.004-0.016, readers 1-3) as well as upper and lower zones (p = 0.004-0.016, readers 1-2). Median transmission grading was indifferent between all lung regions. Intraobserver and interobserver agreements were substantial to almost perfect for grading of both dark-field (κ = 0.793-0.971 and κ = 0.828-0.893) and transmission images (κ = 0.790-0.918 and κ = 0.700-0.772). Pulmonary infiltrates correlated with areas of reduced dark-field signal. Image quality was rated good for dark-field images. CONCLUSIONS: Chest x-ray dark-field images provide information of the lungs complementary to conventional x-ray and allow reliable visual quantification of dark-field signal strength.

Optimization of tube voltage in X-ray dark-field chest radiography.

Grating-based X-ray dark-field imaging is a novel imaging modality which has been refined during the last decade. It exploits the wave-like behaviour of X-radiation and can nowadays be implemented with existing X-ray tubes used in clinical applications. The method is based on the detection of small-angle X-ray scattering, which occurs e.g. at air-tissue-interfaces in the lung or bone-fat interfaces in spongy bone. In contrast to attenuation-based chest X-ray imaging, the optimal tube voltage for dark-field imaging of the thorax has not yet been examined. In this work, dark-field scans with tube voltages ranging from 60 to 120 kVp were performed on a deceased human body. We analyzed the resulting images with respect to subjective and objective image quality, and found that the optimum tube voltage for dark-field thorax imaging at the used setup is at rather low energies of around 60 to 70 kVp. Furthermore, we found that at these tube voltages, the transmission radiographs still exhibit sufficient image quality to correlate dark-field information. Therefore, this study may serve as an important guideline for the development of clinical dark-field chest X-ray imaging devices for future routine use.

Contrast-to-noise ratios and thickness-normalized, ventilation-dependent signal levels in dark-field and conventional in vivo thorax radiographs of two pigs.

Lung tissue causes significant small-angle X-ray scattering, which can be visualized with grating-based X-ray dark-field imaging. Structural lung diseases alter alveolar microstructure, which often causes a dark-field signal decrease. The imaging method provides benefits for diagnosis of such diseases in small-animal models, and was successfully used on porcine and human lungs in a fringe-scanning setup. Micro- and macroscopic changes occur in the lung during breathing, but their individual effects on the dark-field signal are unknown. However, this information is important for quantitative medical evaluation of dark-field thorax radiographs. To estimate the effect of these changes on the dark-field signal during a clinical examination, we acquired in vivo dark-field chest radiographs of two pigs at three ventilation pressures. Pigs were used due to the high degree of similarity between porcine and human lungs. To analyze lung expansion separately, we acquired CT scans of both pigs at comparable posture and ventilation pressures. Segmentation, masking, and forward-projection of the CT datasets yielded maps of lung thickness and logarithmic lung attenuation signal in registration with the dark-field radiographs. Upon correlating this data, we discovered approximately linear relationships between the logarithmic dark-field signal and both projected quantities for all scans. Increasing ventilation pressure strongly decreased dark-field extinction coefficients, whereas the ratio of lung dark-field and attenuation signal changed only slightly. Furthermore, we investigated ratios of dark-field and attenuation noise levels at realistic signal levels via calculations and phantom measurements. Dark-field contrast-to-noise ratio (CNR) per lung height was 5 to 10% of the same quantity in attenuation. We conclude that better CNR performance in the dark-field modality is typically due to greater anatomical noise in the conventional radiograph. Given the high physiological similarity of human and porcine lungs, the presented thickness-normalized, ventilation-dependent values allow estimation of dark-field activity of human lungs of variable size and inspiration, which facilitates the design of suitable clinical imaging setups.