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

Unmanned Aerial Systems for Investigating the Polar Atmospheric Boundary Layer—Technical Challenges and Examples of Applications

Unmanned aerial systems (UAS) fill a gap in high-resolution observations of meteorological parameters on small scales in the atmospheric boundary layer (ABL). Especially in the remote polar areas, there is a strong need for such detailed observations with different research foci. In this study, three systems are presented which have been adapted to the particular needs for operating in harsh polar environments: The fixed-wing aircraft M2AV with a mass of 6 kg, the quadrocopter ALICE with a mass of 19 kg, and the fixed-wing aircraft ALADINA with a mass of almost 25 kg. For all three systems, their particular modifications for polar operations are documented, in particular the insulation and heating requirements for low temperatures. Each system has completed meteorological observations under challenging conditions, including take-offand landing on the ice surface, low temperatures (down to-28 °C), icing, and, for the quadrocopter, under the impact of the rotor downwash. The influence on the measured parameters is addressed here in the form of numerical simulations and spectral data analysis. Furthermore, results from several case studies are discussed: With the M2AV, low-level flights above leads in Antarctic sea ice were performed to study the impact of areas of open water within ice surfaces on the ABL, and a comparison with simulations was performed. ALICE was used to study the small-scale structure and short-term variability of the ABL during a cruise of RV Polarstern to the 79° N glacier in Greenland. With ALADINA, aerosol measurements of different size classes were performed in Ny-Alesund, Svalbard, in highly complex terrain. In particular, very small, freshly formed particles are difficult to monitor and require the active control of temperature inside the instruments. The main aim of the article is to demonstrate the potential of UAS for ABL studies in polar environments, and to provide practical advice for future research activities with similar systems. © 2020 by the authors

Unmanned Aerial Systems for Investigating the Polar Atmospheric Boundary Layer—Technical Challenges and Examples of Applications

Unmanned aerial systems (UAS) fill a gap in high-resolution observations of meteorological parameters on small scales in the atmospheric boundary layer (ABL). Especially in the remote polar areas, there is a strong need for such detailed observations with different research foci. In this study, three systems are presented which have been adapted to the particular needs for operating in harsh polar environments: The fixed-wing aircraft M^2AV with a mass of 6 kg, the quadrocopter ALICE with a mass of 19 kg, and the fixed-wing aircraft ALADINA with a mass of almost 25 kg. For all three systems, their particular modifications for polar operations are documented, in particular the insulation and heating requirements for low temperatures. Each system has completed meteorological observations under challenging conditions, including take-off and landing on the ice surface, low temperatures (down to −28 °C), icing, and, for the quadrocopter, under the impact of the rotor downwash. The influence on the measured parameters is addressed here in the form of numerical simulations and spectral data analysis. Furthermore, results from several case studies are discussed: With the M^2AV, low-level flights above leads in Antarctic sea ice were performed to study the impact of areas of open water within ice surfaces on the ABL, and a comparison with simulations was performed. ALICE was used to study the small-scale structure and short-term variability of the ABL during a cruise of RV Polarstern to the 79°N glacier in Greenland. With ALADINA, aerosol measurements of different size classes were performed in Ny-Ålesund, Svalbard, in highly complex terrain. In particular, very small, freshly formed particles are difficult to monitor and require the active control of temperature inside the instruments. The main aim of the article is to demonstrate the potential of UAS for ABL studies in polar environments, and to provide practical advice for future research activities with similar systems

X-Ray Phase-Contrast Tomography of Renal Ischemia-Reperfusion Damage

Purpose: The aim of the study was to investigate microstructural changes occurring in unilateral renal ischemia-reperfusion injury in a murine animal model using synchrotron radiation. Material and Methods: The effects of renal ischemia-reperfusion were investigated in a murine animal model of unilateral ischemia. Kidney samples were harvested on day 18. Grating-Based Phase-Contrast Imaging (GB-PCI) of the paraffin-embedded kidney samples was performed at a Synchrotron Radiation Facility (beam energy of 19 keV). To obtain phase information, a two-grating Talbot interferometer was used applying the phase stepping technique. The imaging system provided an effective pixel size of 7.5 mu m. The resulting attenuation and differential phase projections were tomographically reconstructed using filtered back-projection. Semi-automated segmentation and volumetry and correlation to histopathology were performed. Results: GB-PCI provided good discrimination of the cortex, outer and inner medulla in non-ischemic control kidneys. Post-ischemic kidneys showed a reduced compartmental differentiation, particularly of the outer stripe of the outer medulla, which could not be differentiated from the inner stripe. Compared to the contralateral kidney, after ischemia a volume loss was detected, while the inner medulla mainly retained its volume (ratio 0.94). Post-ischemic kidneys exhibited severe tissue damage as evidenced by tubular atrophy and dilatation, moderate inflammatory infiltration, loss of brush borders and tubular protein cylinders. Conclusion: In conclusion GB-PCI with synchrotron radiation allows for non-destructive microstructural assessment of parenchymal kidney disease and vessel architecture. If translation to lab-based approaches generates sufficient density resolution, and with a time-optimized image analysis protocol, GB-PCI may ultimately serve as a non-invasive, non-enhanced alternative for imaging of pathological changes of the kidney

Non-specific alterations of craniocervical venous drainage in multiple sclerosis revealed by cardiac-gated phase-contrast MRI

Objective: There is an on-going controversy about venous drainage abnormalities in multiple sclerosis (MS). We applied cardiac-gated phase-contrast and venographic magnetic resonance (MR) techniques to compare venous drainage patterns in patients with MS, healthy controls, and subjects with migraine. Methods: A total of 27 patients with MS (21 female, age 12–59 years, mean disease duration 8.4 ± 8.5 years) and 27 age- and gender-matched healthy controls (21 female, age 12–60 years) were investigated with velocity-encoded cine-phase contrast MR sequences and a 2D time-of-flight MR venography of the cervicocranial region on a 3-T MRI. The data were compared with 26 patients with chronic migraine headaches (19 female, age 17–62 years), previously investigated with the same protocol. The degree of primary and secondary venous outflow in relation to the total cerebral blood flow (tCBF) was compared both quantitatively and qualitatively. Statistical analyses were performed using linear regression models. Results: Secondary venous outflow was significantly increased in patients with MS compared with healthy controls, both qualitatively ( p < 0.001) and quantitatively ( p < 0.013). The observed changes were independent of age and disease duration. Very similar alterations of venous drainage were detectable with the same approach in patients with migraine, without significant differences between MS and migraine patients ( p = 0.65). Conclusion: Our MRI-based study suggests that patients with MS have alterations of cerebral venous drainage similar to subjects with chronic migraine. These non-disease-specific changes seem to a secondary phenomenon rather than being of primary pathogenic importance

Ex Vivo Perfusion-Simulation Measurements of Microbubbles as a Scattering Contrast Agent for Grating-Based X-Ray Dark-Field Imaging.

The investigation of dedicated contrast agents for x-ray dark-field imaging, which exploits small-angle scattering at microstructures for contrast generation, is of strong interest in analogy to the common clinical use of high-atomic number contrast media in conventional attenuation-based imaging, since dark-field imaging has proven to provide complementary information. Therefore, agents consisting of gas bubbles, as used in ultrasound imaging for example, are of particular interest. In this work, we investigate an experimental contrast agent based on microbubbles consisting of a polyvinyl-alcohol shell with an iron oxide coating, which was originally developed for multimodal imaging and drug delivery. Its performance as a possible contrast medium for small-animal angiography was examined using a mouse carcass to realistically consider attenuating and scattering background signal. Subtraction images of dark field, phase contrast and attenuation were acquired for a concentration series of 100%, 10% and 1.3% to mimic different stages of dilution in the contrast agent in the blood vessel system. The images were compared to the gold-standard iodine-based contrast agent Solutrast, showing a good contrast improvement by microbubbles in dark-field imaging. This study proves the feasibility of microbubble-based dark-field contrast-enhancement in presence of scattering and attenuating mouse body structures like bone and fur. Therefore, it suggests a strong potential of the use of polymer-based microbubbles for small-animal dark-field angiography

X-Ray Dark-field Imaging to Depict Acute Lung Inflammation in Mice

Abstract The aim of this study was to evaluate the feasibility of early stage imaging of acute lung inflammation in mice using grating-based X-ray dark-field imaging in vivo. Acute lung inflammation was induced in mice by orotracheal instillation of porcine pancreatic elastase. Control mice received orotracheal instillation of PBS. Mice were imaged immediately before and 1 day after the application of elastase or PBS to assess acute changes in pulmonary structure due to lung inflammation. Subsequently, 6 mice from each group were sacrificed and their lungs were lavaged and explanted for histological analysis. A further 7, 14 and 21 days later the remaining mice were imaged again. All images were acquired with a prototype grating-based small-animal scanner to generate dark-field and transmission radiographs. Lavage confirmed that mice in the experimental group had developed acute lung inflammation one day after administration of elastase. Acute lung inflammation was visible as a striking decrease in signal intensity of the pulmonary parenchyma on dark-field images at day 1. Quantitative analysis confirmed that dark-field signal intensity at day 1 was significantly lower than signal intensities measured at the remaining timepoints, confirming that acute lung inflammation can be depicted in vivo with dark-field radiography

Computer-aided diagnosis of pulmonary diseases using x-ray darkfield radiography

In this work we develop a computer-aided diagnosis (CAD) scheme for classification of pulmonary disease for grating-based x-ray radiography. In addition to conventional transmission radiography, the grating-based technique provides a dark-field imaging modality, which utilizes the scattering properties of the x-rays. This modality has shown great potential for diagnosing early stage emphysema and fibrosis in mouse lungs in vivo. The CAD scheme is developed to assist radiologists and other medical experts to develop new diagnostic methods when evaluating grating-based images. The scheme consists of three stages: (i) automatic lung segmentation; (ii) feature extraction from lung shape and dark-field image intensities; (iii) classification between healthy, emphysema and fibrosis lungs. A study of 102 mice was conducted with 34 healthy, 52 emphysema and 16 fibrosis subjects. Each image was manually annotated to build an experimental dataset. System performance was assessed by: (i) determining the quality of the segmentations; (ii) validating emphysema and fibrosis recognition by a linear support vector machine using leave-one-out cross-validation. In terms of segmentation quality, we obtained an overlap percentage (&Omega;) 92.63 &plusmn; 3.65%, Dice Similarity Coefficient (DSC) 89.74 &plusmn; 8.84% and Jaccard Similarity Coefficient 82.39 &plusmn; 12.62%. For classification, the accuracy, sensitivity and specificity of diseased lung recognition was 100%. Classification between emphysema and fibrosis resulted in an accuracy of 93%, whilst the sensitivity was 94% and specificity 88%. In addition to the automatic classification of lungs, deviation maps created by the CAD scheme provide a visual aid for medical experts to further assess the severity of pulmonary disease in the lung, and highlights regions affected