Improved In vivo Assessment of Pulmonary Fibrosis in Mice using X-Ray Dark-Field Radiography

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with a median life expectancy of 4-5 years after initial diagnosis. Early diagnosis and accurate monitoring of IPF are limited by a lack of sensitive imaging techniques that are able to visualize early fibrotic changes at the epithelial-mesenchymal interface. Here, we report a new x-ray imaging approach that directly visualizes the air-tissue interfaces in mice in vivo. This imaging method is based on the detection of small-angle x-ray scattering that occurs at the air-tissue interfaces in the lung. Small-angle scattering is detected with a Talbot-Lau interferometer, which provides the so-called x-ray dark-field signal. Using this imaging modality, we demonstrate-for the first time-the quantification of early pathogenic changes and their correlation with histological changes, as assessed by stereological morphometry. The presented radiography method is significantly more sensitive in detecting morphological changes compared with conventional x-ray imaging, and exhibits a significantly lower radiation dose than conventional x-ray CT. As a result of the improved imaging sensitivity, this new imaging modality could be used in future to reduce the number of animals required for pulmonary research studies

Depiction of pneumothoraces in a large animal model using x-ray dark-field radiography

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

Depiction of pneumothoraces in a large animal model using x-ray dark-field radiography

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-tonoise 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

In-vivo X-ray Dark-Field Chest Radiography of a Pig

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 x 35 cm(2)) of a living pig, acquired with clinically compatible parameters (40 s scan time, approx. 80 mu Sv 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

X-ray dark-field imaging of the human lung-A feasibility study on a deceased body

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

Grating-based X-ray dark-field imaging : a new paradigm in radiography

Grating-based X-ray dark-field contrast is an emerging new imaging modality that is demonstrating particularly high potential for radiography. The signal in dark-field X-ray imaging is determined by small-angle X-ray scattering at structures typically below the spatial resolution of the imaging setup. Thus, this technique not only yields complementary information but also visualizes information that lies under the resolution limit for conventional, absorption-based radiography. Grating-based X-ray dark-field imaging has been shown to be feasible with both synchrotron radiation and conventional X-ray tubes. Lung, breast, and bone imaging have been identified as the applications promising the main impact, but other applications are on the horizon. Specifically, dark-field radiography has been used to detect pulmonary emphysema and assesses its regional distribution in mice and holds promise to improve the visualization of micro-calcifications in mammography and yields information about bone microstructure. Further technical developments are required to make the technique suitable for clinical use

Contrast-to-noise ratio optimization for a prototype phase-contrast computed tomography scanner.

In the field of biomedical X-ray imaging, novel techniques, such as phase-contrast and dark-field imaging, have the potential to enhance the contrast and provide complementary structural information about a specimen. In this paper, a first prototype of a preclinical X-ray phase-contrast CT scanner based on a Talbot-Lau interferometer is characterized. We present a study of the contrast-to-noise ratios for attenuation and phase-contrast images acquired with the prototype scanner. The shown results are based on a series of projection images and tomographic data sets of a plastic phantom in phase and attenuation-contrast recorded with varying acquisition settings. Subsequently, the signal and noise distribution of different regions in the phantom were determined. We present a novel method for estimation of contrast-to-noise ratios for projection images based on the cylindrical geometry of the phantom. Analytical functions, representing the expected signal in phase and attenuation-contrast for a circular object, are fitted to individual line profiles of the projection data. The free parameter of the fit function is used to estimate the contrast and the goodness of the fit is determined to assess the noise in the respective signal. The results depict the dependence of the contrast-to-noise ratios on the applied source voltages, the number of steps of the phase stepping routine, and the exposure times for an individual step. Moreover, the influence of the number of projection angles on the image quality of CT slices is investigated. Finally, the implications for future imaging purposes with the scanner are discussed

Results from the first preclinical CT scanner with grating based phase contrast and a rotating gantry

After successful demonstrations of soft-tissue phase-contrast imaging with grating interferometers at synchrotron radiation sources and at laboratory based x-ray tubes, a first preclinical CT scanner with grating based phase contrast imaging modality has been constructed. The rotating gantry is equipped with a three-grating interferometer, a 50 watt tungsten anode source and a Hamamatsu flat panel detector. The total length of the interferometer is 45 cm, and the bed of the scanner is optimized for mice, with a scanning diameter of 35 mm. From one single scan both phase-contrast and standard attenuation based tomography can be attained, providing an overall gain in image contrast

Non-binary phase gratings for x-ray imaging with a compact Talbot interferometer

X-ray imaging using a Talbot-Lau interferometer, consisting of three binary gratings, is a well-established approach to acquire x-ray phase-contrast and dark-field images with a polychromatic source. However, challenges in the production of high aspect ratio gratings limit the construction of a compact setup for high x-ray energies. In this study we consider the use of phase gratings with triangular-shaped structures in an x-ray interferometer and show that such gratings can yield high visibilities for significantly shorter propagation distances than conventional gratings with binary structures. The findings are supported by simulation and experimental results for both cases of a monochromatic and a polychromatic source