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The aim of this study was to assess the diagnostic value of x-ray dark-field radiography to detect pneumothoraces in a pig model. Eight pigs were imaged with an experimental grating-based large-animal dark-field scanner before and after induction of a unilateral pneumothorax. Image contrast-to-noise ratios between lung tissue and the air-filled pleural cavity were quantified for transmission and dark-field radiograms. The projected area in the object plane of the inflated lung was measured in dark-field images to quantify the collapse of lung parenchyma due to a pneumothorax. Means and standard deviations for lung sizes and signal intensities from dark-field and transmission images were tested for statistical significance using Student’s two-tailed t-test for paired samples. The contrast-to-noise ratio between the air-filled pleural space of lateral pneumothoraces and lung tissue was significantly higher in the dark-field (3.65 ± 0.9) than in the transmission images (1.13 ± 1.1; p = 0.002). In case of dorsally located pneumothoraces, a significant decrease (−20.5%; p > 0.0001) in the projected area of inflated lung parenchyma was found after a pneumothorax was induced. Therefore, the detection of pneumothoraces in x-ray dark-field radiography was facilitated compared to transmission imaging in a large animal model.

Contains fulltext : 196944.pdf (Publisher’s version ) (Open Access) Disorders of the lungs such as chronic obstructive pulmonary disease (COPD) are a major cause of chronic morbidity and mortality and the third leading cause of death in the world. The absence of sensitive diagnostic tests for early disease stages of COPD results in under-diagnosis of this treatable disease in an estimated 60-85% of the patients. In recent years a grating-based approach to X-ray dark-field contrast imaging has shown to be very sensitive for the detection and quantification of pulmonary emphysema in small animal models. However, translation of this technique to imaging systems suitable for humans remains challenging and has not yet been reported. In this manuscript, we present the first X-ray dark-field images of in-situ human lungs in a deceased body, demonstrating the feasibility of X-ray dark-field chest radiography on a human scale. Results were correlated with findings of computed tomography imaging and autopsy. The performance of the experimental radiography setup allows acquisition of multi-contrast chest X-ray images within clinical boundary conditions, including radiation dose. Upcoming clinical studies will have to demonstrate that this technology has the potential to improve early diagnosis of COPD and pulmonary diseases in general.

Background Currently, the detection of retained wood is a frequent but challenging task in emergency care. The purpose of this study is to demonstrate improved foreign-body detection with the novel approach of preclinical X-ray dark-field radiography. Methods At a preclinical dark-field x-ray radiography, setup resolution and sensitivity for simultaneous detection of wooden and metallic particles have been evaluated in a phantom study. A clinical setting has been simulated with a formalin fixated human hand where different typical foreign-body materials have been inserted. Signal-to-noise ratios (SNR) have been determined for all test objects. Results On the phantom, the SNR value for wood in the dark-field channel was strongly improved by a factor 6 compared to conventional radiography and even compared to the SNR of an aluminium structure of the same size in conventional radiography. Splinters of wood

X-ray chest radiography is an inexpensive and broadly available tool for initial assessment of the lung in clinical routine, but typically lacks diagnostic sensitivity for detection of pulmonary diseases in their early stages. Recent X-ray dark-field (XDF) imaging studies on mice have shown significant improvements in imaging-based lung diagnostics. Especially in the case of early diagnosis of chronic obstructive pulmonary disease (COPD), XDF imaging clearly outperforms conventional radiography. However, a translation of this technique towards the investigation of larger mammals and finally humans has not yet been achieved. In this letter, we present the first in-vivo XDF full-field chest radiographs (32 × 35 cm2) of a living pig, acquired with clinically compatible parameters (40 s scan time, approx. 80 µSv dose). For imaging, we developed a novel high-energy XDF system that overcomes the limitations of currently established setups. Our XDF radiographs yield sufficiently high image quality to enable radiographic evaluation of the lungs. We consider this a milestone in the bench-to-bedside translation of XDF imaging and expect XDF imaging to become an invaluable tool in clinical practice, both as a general chest X-ray modality and as a dedicated tool for high-risk patients affected by smoking, industrial work and indoor cooking.

Purpose: To evaluate the performance of an experimental X-ray dark-field radiography system for chest imaging in humans and to compare with conventional diagnostic imaging. Materials and Methods: The study was institutional review board (IRB) approved. A single human cadaver (52 years, female, height: 173 cm, weight: 84 kg, chest circumference: 97 cm) was imaged within 24 hours post mortem on the experimental x-ray dark-field system. In addition, the cadaver was imaged on a clinical CT system to obtain a reference scan. The grating-based dark-field radiography setup was equipped with a set of three gratings to enable grating-based dark-field contrast x-ray imaging. The prototype operates at an acceleration voltage of up to 70 kVp and with a field-of-view large enough for clinical chest x-ray (>35 x 35 cm2). Results: It was feasible to extract x-ray dark-field signal of the whole human thorax, clearly demonstrating that human x-ray dark-field chest radiography is feasible. Lung tissue produced strong scattering, reflected in a pronounced x-ray dark-field signal. The ribcage and the backbone are less prominent than the lung but are also distinguishable. Finally, the soft tissue is not present in the dark-field radiography. The regions of the lungs affected by edema, as verified by CT, showed less dark-field signal compared to healthy lung tissue. Conclusion: Our results reveal the current status of translating dark-field imaging from a micro (small animal) scale to a macro (patient) scale. The performance of the experimental x-ray dark-field radiography setup offers, for the first time, obtaining multi-contrast chest x-ray images (attenuation and dark-field signal) from a human cadaver.

X-ray grating-based interferometry promises unique new diagnostic possibilities in medical imaging and materials analysis. To transfer this method from scientific laboratories or small-animal applications to clinical radiography applications, compact setups with a large field of view (FoV) are required. Currently the FoV is limited by the grating area, which is restricted due to the complex manufacturing process. One possibility to increase the FoV is tiling individual grating tiles to create one large area grating mounted on a carrier substrate. We investigate theoretically the accuracy needed for a tiling process in all degrees of freedom by applying a simulation approach. We show how the resulting precision requirements can be met using a custom-built frame for exact positioning. Precise alignment is achieved by comparing the fringe patterns of two neighboring grating tiles in a grating interferometer. With this method, the FoV can be extended to practically any desired length in one dimension. First results of a phase-contrast scanning setup with a full FoV of 384 mm × 24 mm show the suitability of this method.

Purpose: The purpose of the present study was to evaluate if x-ray dark-field imaging can help to visualize lung cancer in mice. Materials and Methods: The experiments were performed using mutant mice with high-grade adenocarcinomas. Eight animals with pulmonary carcinoma and eight control animals were imaged in radiography mode using a prototype small-animal x-ray dark-field scanner and three of the cancerous ones additionally in CT mode. After imaging, the lungs were harvested for histological analysis. To determine their diagnostic value, x-ray dark-field and conventional attenuation images were analyzed by three experienced readers in a blind assessment. Results radiographic imaging: The lung nodules were much clearer visualized on the dark-field radiographs compared to conventional radiographs. The loss of air-tissue interfaces in the tumor leads to a significant loss of x-ray scattering, reflected in a strong dark-field signal change. The difference between tumor and healthy tissue in terms of x-ray attenuation is significantly less pronounced. Furthermore, the signal from the overlaying structures on conventional radiographs complicates the detection of pulmonary carcinoma. Results CT imaging: The very first in-vivo CT-imaging results are quite promising as smaller tumors are often better visible in the dark-field images. However the imaging quality is still quite low, especially in the attenuation images due to un-optimized scanning parameters. Conclusion: We found a superior diagnostic performance of dark-field imaging compared to conventional attenuation based imaging, especially when it comes to the detection of small lung nodules. These results support the motivation to further develop this technique and translate it towards a clinical environment.

Background: Mechanical ventilation (MV) and the supplementation of oxygen-rich gas, often needed in postnatal resuscitation procedures, are known to be main risk factors for impaired pulmonary development in the preterm and term neonates. We analyzed whether the advance from conventional x-ray technology to x-ray dark-field radiography can improve visualization of early lung injury induced by MV and hyperoxia in neonatal mice. Methods: 5-7-day-old wild type C57BL/6 mice were mechanically ventilated with oxygen-enriched gas (MV-O 2 ; FiO 2 0.4) for 2 or 8 hours. Unventilated, spontaneously breathing littermates were kept in FiO 2 0.4 for 2 and 8 hours or in room air. After pulmonary function testing, the animals were imaged using a prototype small-animal x-ray dark-field scanner before standardized fixation for histologic analysis. Results: X-ray dark field of neonatal mice undergoing hyperoxia and MV-O2 revealed increasing loss of x-ray small-angle scattering when compared to the images obtained from animals kept in room air. The observed changes assessed by imaging correlated well with results of histologic analysis and were found to yield superior differentiation than lung function testing. Conclusion: The present study was able to show, that X-ray dark-field radiography acquired with a grating interferometer visualizes already minor changes in the morphology of the developing lung, caused by hyperoxia or MV-O 2 . In the future, this imaging technique can be applied to provide early diagnosis and monitor treatment regimen in neonatal lung injury by appropriate surveillance protocols.

Accounting for about 1.5 million deaths annually, lung cancer is the prevailing cause of cancer deaths worldwide, mostly associated with long-term smoking effects. Numerous small-animal studies are performed currently in order to better understand the pathogenesis of the disease and to develop treatment strategies. Within this letter, we propose to exploit X-ray dark-field imaging as a novel diagnostic tool for the detection of lung cancer on projection radiographs. Here, we demonstrate in living mice bearing lung tumors, that X-ray dark-field radiography provides significantly improved lung tumor detection rates without increasing the number of false-positives, especially in the case of small and superimposed nodules, when compared to conventional absorption-based imaging. While this method still needs to be adapted to larger mammals and finally humans, the technique presented here can already serve as a valuable tool in evaluating novel lung cancer therapies, tested in mice and other small animal models.

Differential phase-contrast X-ray imaging using a Talbot-Lau interferometer has recently shown promising results for applications in medical imaging. However, reducing the applied radiation dose remains a major challenge. In this study, we consider the realization of a Talbot-Lau interferometer in a high Talbot order to increase the signal-to-noise ratio for low-dose applications. The quantitative performance of π and π/2 systems at high Talbot orders is analyzed through simulations, and the design energy and X-ray spectrum are optimized for mammography. It is found that operation even at very high Talbot orders is feasible and beneficial for image quality. As long as the X-ray spectrum is matched to the visibility spectrum, the SNR continuously increases with the Talbot order for π-systems. We find that the optimal X-ray spectra and design energies are almost independent of the Talbot order and that the overall imaging performance is robust against small variations in these parameters. Discontinuous spectra, such as that from molybdenum, are less robust because the characteristic lines may coincide with minima in the visibility spectra; however, they may offer slightly better performance. We verify this hypothesis by realizing a prototype system with a mean fringe visibility of above 40% at the seventh Talbot order. With this prototype, a proof-of-principle measurement of a freshly dissected breast at reasonable compression to 4 cm is conducted with a mean glandular dose of only 3 mGy but with a high SNR.

Phase-contrast mammography using laboratory X-ray sources is a promising approach to overcome the relatively low sensitivity and specificity of clinical, absorption-based screening. Current research is mostly centered on identifying potential diagnostic benefits arising from phase-contrast and dark-field mammography and benchmarking the latter with conventional state-of-the-art imaging methods. So far, little effort has been made to adjust this novel imaging technique to clinical needs. In this article, we address the key points for a successful implementation to a clinical routine in the near future and present the very first dose-compatible and rapid scan-time phase-contrast mammograms of both a freshly dissected, cancer-bearing mastectomy specimen and a mammographic accreditation phantom.