Search

Pleural epithelial adaptations to mechanical stress are relevant to both normal lung function and parenchymal lung diseases. Assessing regional differences in mechanical stress, however, has been complicated by the nonlinear stress-strain properties of the lung and the large displacements with ventilation. Moreover, there is no reliable method of isolating pleural epithelium for structural studies. To define the topographic variation in pleural structure, we developed a method of en face harvest of murine pleural epithelium. Silver-stain was used to highlight cell borders and facilitate imaging with light microscopy. Machine learning and watershed segmentation were used to define the cell area and cell perimeter of the isolated pleural epithelial cells. In the deflated lung at residual volume, the pleural epithelial cells were significantly larger in the apex (624 ± 247 μm

Mammalian pulmonary arteries divide multiple times before reaching the vast capillary network of the alveoli. Morphological analyses of the arterial branches can be challenging because more proximal branches are likely biologically distinct from more peripheral parts. Thus, it is useful to group the arterial branches into groups of coherent biology. While the generational approach of dichotomous branching is straightforward, the grouping of arterial branches in the asymmetrically branching monopodial lung is less clear. Several established classification methods return highly dissimilar groupings when employed on the same organ. Here, we established a workflow allowing the quantification of grouping results for the monopodial lung and tested various methods to group the branches of the arterial tree into coherent groups. A mouse lung was imaged by synchrotron x-ray microcomputed tomography, and the arteries were digitally segmented. The arterial tree was divided into its individual segments, morphological properties were assessed from corresponding light microscopic scans, and different grouping methods were employed, such as (fractal) generation or (Strahler) order. The results were ranked by the morphological similarity within and dissimilarity between the resulting groups. Additionally, a method from the mathematical field of cluster analysis was employed for creating a reference classification. In conclusion, there were significant differences in method performance. The Strahler order was significantly superior to the generation system commonly used to classify human lung structure. Furthermore, a clustering approach indicated more precise ways to classify the monopodial lung vasculature exist.

Improving the scalability of tissue imaging throughput with bright, coherent X-rays requires identifying and mitigating artifacts resulting from the interactions between X-rays and matter. At synchrotron sources, long-term imaging of soft tissues in solution can result in gas bubble formation or cavitation, which dramatically compromises image quality and integrity of the samples. By combining in-line phase-contrast cineradiography withoperandogas chromatography, we were able to track the onset and evolution of high-energy X-ray-induced gas bubbles in ethanol-embedded soft tissue samples for tens of minutes (2 to 3 times the typical scan times). We demonstrate quantitatively that vacuum degassing of the sample during preparation can significantly delay bubble formation, offering up to a twofold improvement in dose tolerance, depending on the tissue type. However, once nucleated, bubble growth is faster in degassed than undegassed samples, indicating their distinct metastable states at bubble onset. Gas chromatography analysis shows increased solvent vaporization concurrent with bubble formation, yet the quantities of dissolved gases remain unchanged. Coupling features extracted from the radiographs with computational analysis of bubble characteristics, we uncover dose-controlled kinetics and nucleation site-specific growth. These hallmark signatures provide quantitative constraints on the driving mechanisms of bubble formation and growth. Overall, the observations highlight bubble formation as a critical, yet often overlooked hurdle in upscaling X-ray imaging for biological tissues and soft materials and we offer an empirical foundation for their understanding and imaging protocol optimization. More importantly, our approaches establish a top-down scheme to decipher the complex, multiscale radiation-matter interactions in these applications.Significance statementBetter probing the X-ray radiation dose limit of bubble formation in biological tissue and developing mitigation methods is essential for improving imaging techniques involving X-ray, such as synchrotron X-ray tomography or crystallography. Here, we combinedoperandogas chromatography with in-line X-ray phase-contrast radiography on human lung and brain tissue to investigate bubble formation under high-energy X-ray irradiation. We demonstrate that vacuum degassing delays bubble nucleation up to a factor two, depending on the tissue type. Gas chromatography analysis showed increased solvent vaporization during bubble formation; however, the quantities of dissolved gases remained unchanged. Moreover, depending on the nucleation site, bubble growth can be geometrically constrained by sample microstructure, which influence its dynamics.

Klinisch wird COVID-19 („corona virus disease“ 2019) zunehmend als systemische Erkrankung gesehen, in deren Zentrum eine Multiorganbeteiligung durch einen hyperkoagulatorischen Zustand im Sinne einer Vaskulopathie steht. Eine Behandlung mit Thrombozytenfunktionshemmern oder Heparinen erscheint die logische Konsequenz. Die aktuelle Studienlage, zumindest fur ASS, ergibt allerdings keine Hinweise auf eine Wirksamkeit. Entsprechend der zu nennenswerten Anteilen primar mikrostrukturellen Gefasveranderungen sollte die radiologische Diagnostik nicht nur Makrogefaspathologien, sondern auch Hinweise auf diffuse Perfusionsstorungen darstellen. In der Lunge sind beispielsweise Perfusionsausfalle nachweisbar, die nur teilweise durch pulmonalarterielle Fullungsdefekte zu erklaren sind. Ahnliche Befunde zeigen sich in fast allen Organsystemen. Eine therapeutische Intervention mittels niedermolekularer Heparine bei hospitalisierten Patienten in situationsadaptierter Dosierung ist indiziert und wird ausfuhrlich besprochen. Bei Nachweis von Mikro- und Makrogefasthrombosierung im Rahmen von COVID-19 spielt die erweiterte radiologische Diagnostik eine zentrale Rolle und ist die Basis der Therapie und Sekundarpravention.

Hydrogels provide a promising method for the targeted delivery of protein drugs. Loading the protein drug into the hydrogel free volume can be challenging due to limited quantities of the drug (e.g., growth factor) and complex physicochemical properties of the hydrogel. Here, we investigated both passive and active loading of the heteropolysaccharide hydrogel pectin. Passive loading of glass phase pectin films was evaluated by contact angles and fractional thickness of the pectin films. Four pectin sources demonstrated mean contact angles of 88° with water and 122° with pleural fluid (p < 0.05). Slow kinetics and evaporative losses precluded passive loading. In contrast, active loading of the translucent pectin films was evaluated with the colorimetric tracer methylene blue. Active loading parameters were systematically varied and recorded at 500 points/s. The distribution of the tracer was evaluated by image morphometry. Active loading of the tracer into the pectin films required the optimization of probe velocity, compression force, and contact time. We conclude that active loading using pectin-specific conditions is required for the efficient embedding of low viscosity liquids into pectin hydrogels.

Pectin is a plant-derived heteropolysaccharide that has been implicated in drug development, tissue engineering, and visceral organ repair. Pectin demonstrates remarkable biostability in a variety of physiologic environments but is biodegradable in water. To understand the dynamics of pectin biodegradation in basic environments, we developed a microfluidics system that facilitated the quantitative comparison of pectin films exposed to facial erosion. Pectin biodegradation was assessed using fluorescein tracer embedded in pectin, trypan blue quenching of released fluorescence, and highly sensitive microfluorimetry. The microfluidic perfusate, delivered through 6 um-pore synthetic membrane interface, demonstrated nonlinear erosion of the pectin film; 75% of tracer was released in 28 h. The microfluidics system was used to identify potential modifiers of pectin erosion. The polyphenolic compound tannic acid, loaded into citrus pectin films, demonstrated a dose-dependent decrease in pectin erosion. Tannic acid had no detectable impact on the physical properties of citrus pectin including adhesivity and cohesion. In contrast, tannic acid weakened the burst strength and cohesion of pectins derived from soy bean and potato sources. We conclude that facial erosion may explain the biostability of citrus pectin on visceral organ surfaces as well as provide a useful method for identifying modifiers of citrus pectin biodegradation.

Over the last decade, a fundamentally new type of computed tomography (CT) detectors has proved its superior capabilities in both physical and preclinical evaluations and is now approaching the stage of clinical practice. These detectors are able to discriminate single photons and quantify their energy and are hence called photon-counting detectors. Among the promising benefits of this technology are improved radiation dose efficiency, increased contrast-to-noise ratio, reduced metal artifacts, improved spatial resolution, simultaneous multi-energy acquisitions, and the prospect of multi-phase imaging within a single acquisition using multiple contrast agents. Taking the conventional energy-integrating detectors as a reference, the authors demonstrate the technical principles of this new technology and provide phantom and patient images acquired by a whole-body photon-counting CT. These images serve as a basis for discussing the potential future of clinical CT.

Cirrhosis describes the development of excess fibrous tissue around regenerative nodules in response to chronic liver injury and usually leads to irreversible organ damage and end-stage liver disease. During the development of cirrhosis, the formation of collagenous scar tissue is paralleled by a reorganization and remodeling of the hepatic vascular system. To date, macrovascular remodeling in various cirrhosis models has been examined using three-dimensional (3D) imaging modalities, while microvascular changes have been studied mainly by two-dimensional (2D) light microscopic and electron microscopic imaging. Here, we report on the application of high-resolution 3D synchrotron radiation-based microtomography (SRμCT) for the study of the sinusoidal and capillary blood vessel system in three murine models of advanced parenchymal and biliary hepatic fibrosis. SRμCT facilitates the characterization of microvascular architecture and identifies features of intussusceptive angiogenesis in progressive liver fibrosis in a non-destructive 3D manner.

Hintergrund Klinisch ist COVID-19 (Corona Virus Disease 2019) mit einem breiten Spektrum an Symptomen verbunden, das von milden Beschwerden eines oberen Atemwegsinfekts bis zur lebensbedrohlichen hypoxischen respiratorischen Insuffizienz und Multiorganversagen reichen kann. Fragestellung Zu den initial identifizierten pulmonalen Schädigungsmustern, wie dem diffusen Alveolarschaden bei akutem Lungenversagen, gesellen sich neue Erkenntnisse, die ein komplexeres Szenario zeichnen. Hierzu gehören Mikrogefäßbeteiligungen und ein breites Spektrum assoziierter Pathologien multipler Organsysteme. Eine Rückskalierung mikrostruktureller Gefäßveränderungen ist durch gezielte Korrelation pathologischer Obduktionsergebnisse mit radiologischer Bildgebung möglich. Material und Methoden Radiologisch-pathologische Korrelation und mikroradiologische Bildgebung zur Untersuchung der Mikrogefäßbeteiligung bei letaler COVID-19. Ergebnisse Die Fälle zweier COVID-19-Patienten werden präsentiert. Patient 1 zeigte eine relative Minderperfusion in Lungenarealen, die radiologisch keine COVID-19-typischen Infiltrate aufwiesen; die gezielte autoptische Korrelation ergab auch in diesen Lungenabschnitten bereits subtile Zeichen eines Mikrogefäßschadens. Patient 2 zeigte radiologisch und pathologisch eine fortgeschrittene COVID-19-typische Lungenstrukturdestruktion; der Fall illustriert die Schädigungsmuster der Blut-Luft-Schranke. Die CT-morphologisch perfusionsgestörte Darmwand von Patient 2 konnte letztendlich mikroskopisch nicht eindeutig auf einen intestinalen Mikrogefäßschäden zurückgeführt werden. Schlussfolgerung Die Ergebnisse weisen neben der Mikrogefäßthrombosierung auf eine funktionelle pulmonale Vasodysregulation im Rahmen der vaskulären Phase von COVID-19 hin. Hervorzuheben sind die klinische Relevanz von Obduktionen und eine enge Verzahnung von radiologischen Bildbefunden mit histopathologischen Schädigungsmustern zum besseren Verständnis von COVID-19.

Pectin’s unique physicochemical properties have been linked to a variety of reparative and regenerative processes in nature. To investigate the effect of water on pectin repair, we used a 5 mm stainless-steel uniaxial load to fracture glass phase pectin films. The fractured gel phase films were placed on a 1.5–1.8 mm thick layer of water and incubated for 8 h at room temperature and ambient humidity. There was no immersion or agitation. The repaired pectin film was subsequently assessed for its optical and mechanical properties. Light microscopy demonstrated repair of the detectable fracture area and restoration of the films’ optical properties. The burst strength of the repaired film declined to 55% of the original film. However, its resilience was restored to 87% of the original film. Finally, a comparison of the initial and post-repair fracture patterns demonstrated no recurrent fissures in the repaired glass phase films. The water-induced repair of the pectin film was superior to the optical and mechanical properties of the repaired films composed of nanocellulose fibers, sodium hyaluronate, and oxidized cellulose. We conclude that the unique physicochemical properties of pectin facilitate the water-induced self-repair of fractured pectin films.

Pectin is a heteropolysaccharide responsible for the structural integrity of the cell walls of terrestrial plants. When applied to the surface of mammalian visceral organs, pectin films form a strong physical bond with the surface glycocalyx. A potential mechanism of pectin adhesion to the glycocalyx is the water-dependent entanglement of pectin polysaccharide chains with the glycocalyx. A better understanding of such fundamental mechanisms regarding the water transport dynamics in pectin hydrogels is of importance for medical applications, e.g., surgical wound sealing. We report on the water transport dynamics in hydrating glass-phase pectin films with particular emphasis on the water content at the pectin-glycocalyceal interface. We used label-free 3D stimulated Raman scattering (SRS) spectral imaging to provide insights into the pectin-tissue adhesive interface without the confounding effects of sample fixation, dehydration, shrinkage, or staining.

Technological advancements in X-ray imaging using bright and coherent synchrotron sources now allows to decouple sample size and resolution, while maintaining high sensitivity to the microstructure of soft, partially dehydrated tissues. The recently developed imaging technique, hierarchical phase-contrast tomography, is a comprehensive approach to address the challenge of organ-scale (up to tens of centimeters) soft tissue imaging with resolution and sensitivity down to the cellular level. Using this technique, we imaged ex vivo an entire human left lung at an isotropic voxel size of 25.08 μm along with local zooms down to 6.05 - 6.5 μm and 2.45 - 2.5 μm in voxel size. The high tissue contrast offered by the fourth-generation synchrotron source at the European Synchrotron Radiation Facility reveals complex multiscale anatomical constitution of the human lung from the macroscopic (centimeter) down to the microscopic (micrometer) scale. The dataset provides complete organ-scale 3D information of the secondary pulmonary lobules and delineates the microstructure of lung nodules with unprecedented detail.

American journal of respiratory and critical care medicine : AJRCCM 205(1), 121-125 (2022). doi:10.1164/rccm.202103-0594IM, Published by American Thoracic Society, New York, NY

Imaging intact human organs from the organ to the cellular scale in three dimensions is a goal of biomedical imaging. To meet this challenge, we developed hierarchical phase-contrast tomography (HiP-CT), an X-ray phase propagation technique using the European Synchrotron Radiation Facility (ESRF)’s Extremely Brilliant Source (EBS). The spatial coherence of the ESRF-EBS combined with our beamline equipment, sample preparation and scanning developments enabled us to perform non-destructive, three-dimensional (3D) scans with hierarchically increasing resolution at any location in whole human organs. We applied HiP-CT to image five intact human organ types: brain, lung, heart, kidney and spleen. HiP-CT provided a structural overview of each whole organ followed by multiple higher-resolution volumes of interest, capturing organotypic functional units and certain individual specialized cells within intact human organs. We demonstrate the potential applications of HiP-CT through quantification and morphometry of glomeruli in an intact human kidney and identification of regional changes in the tissue architecture in a lung from a deceased donor with coronavirus disease 2019 (COVID-19).

Pleural injuries and the associated “air leak” are the most common complications after pulmonary surgery. Air leaks are the primary reason for prolonged chest tube use and increased hospital length of stay. Pectin, a plant-derived heteropolysaccharide, has been shown to be an air-tight sealant of pulmonary air leaks. Here, we investigate the morphologic and mechanical properties of pectin adhesion to the visceral pleural surface of the lung. After the application of high-methoxyl citrus pectin films to the murine lung, we used scanning electron microscopy to demonstrate intimate binding to the lung surface. To quantitatively assess pectin adhesion to the pleural surface, we used a custom adhesion test with force, distance, and time recordings. These assays demonstrated that pectin–glycocalyceal tensile adhesive strength was greater than nanocellulose fiber films or pressure-sensitive adhesives (p &lt, 0.001). Simultaneous videomicroscopy recordings demonstrated that pectin–glycocalyceal adhesion was also stronger than the submesothelial connective tissue as avulsed surface remnants were visualized on the separated pectin films. Finally, pleural abrasion and hyaluronidase enzyme digestion confirmed that pectin binding was dependent on the pleural glycocalyx (p &lt, 0.001). The results indicate that high methoxyl citrus pectin is a promising sealant for the treatment of pleural lung injuries.

Pulmonary veno‐occlusive disease (PVOD) is a rare lung disease characterized by fibrotic narrowing of pulmonary veins leading to pulmonary hypertension (PH) and finally to death by right heart failure. PVOD is often accompanied by pulmonary capillary hemangiomatosis (PCH), a marked abnormal proliferation of pulmonary capillaries. Both morphological patterns often occur together and are thought to be distinct manifestations of the same disease process and accordingly are classified together in group 1′ of the Nice classification of PH. The underlying mechanisms of these aberrant remodeling processes remain poorly understood. In this study, we investigated the three‐dimensional structure of these vascular lesions in the lung explant of a patient diagnosed with PVOD by μ‐computed tomography, microvascular corrosion casting, electron microscopy, immunohistochemistry, correlative light microscopy and gene expression analysis. We were able to describe multifocal intussusceptive neoangiogenesis and vascular sprouting as the three‐dimensional correlate of progressive PCH, a process dividing pre‐existing vessels by intravascular pillar formation previously only known from embryogenesis and tumor neoangiogenesis. Our findings suggest that venous occlusions in PVOD increase shear and stretching forces in the pulmonary capillary bloodstream and thereby induce intussusceptive neoangiogenesis. These findings can serve as a basis for novel approaches to the analysis of PVOD.

Anastomotic leakage is a frequent complication of intestinal surgery and a major source of surgical morbidity. The timing of anastomotic failures suggests that leaks are the result of inadequate mechanical support during the vulnerable phase of wound healing. To identify a biomaterial with physical and mechanical properties appropriate for assisted anastomotic healing, we studied the adhesive properties of the plant-derived structural heteropolysaccharide called pectin. Specifically, we examined high methoxyl citrus pectin films at water contents between 17–24% for their adhesivity to ex vivo porcine small bowel serosa. In assays of tensile adhesion strength, pectin demonstrated significantly greater adhesivity to the serosa than either nanocellulose fiber (NCF) films or pressure sensitive adhesives (PSA) (p &lt, 0.001). Similarly, in assays of shear resistance, pectin demonstrated significantly greater adhesivity to the serosa than either NCF films or PSA (p &lt, 0.001). Finally, the pectin films were capable of effectively sealing linear enterotomies in a bowel simulacrum as well as an ex vivo bowel segment. We conclude that pectin is a biomaterial with physical and adhesive properties capable of facilitating anastomotic healing after intestinal surgery.

Bronchiectasis is a chronic pathological condition characterised by abnormal enlargement of the lung's conductive airways. It is associated with a lack of ciliary motility and restricted mucociliary clearance in diseases such as primary ciliary dyskinesia (PCD) or “immotile cilia syndrome”. Recent studies have shown an increase in the prevalence of bronchiectasis, causing a significant burden on public healthcare systems [1, 2]. The mechanisms that trigger and drive the development of bronchiectasis have yet to be fully elucidated. Murine models of immotile cilia or reduced mucociliary clearance failed to display signs of bronchiectasis in multiple studies, raising questions about the suitability of murine models for non-cystic fibrosis (CF) bronchiectasis and hindering the development of targeted therapies [3]., Synchrotron-based imaging allows for detection of bronchiectasis-like phenotypes in mice with mucociliary clearance disorders https://bit.ly/3gXGdP3

Human organs are complex, three-dimensional and multiscale systems. Spatially mapping the human body down through its hierarchy, from entire organs to their individual functional units and specialised cells, is a major obstacle to fully understanding health and disease. To meet this challenge, we developed hierarchical phase-contrast tomography (HiP-CT), an X-ray phase propagation technique utilising the European Synchrotron Radiation Facility’s Extremely Brilliant Source: the world’s first high-energy 4th generation X-ray source. HiP-CT enabled three-dimensional and non-destructive imaging at near-micron resolution in soft tissues at one hundred thousand times the voxel size whilst maintaining the organ’s structure. We applied HiP-CT to image five intact human parenchymal organs: brain, lung, heart, kidney and spleen. These were hierarchically assessed with HiP-CT, providing a structural overview of the whole organ alongside detail of the organ’s individual functional units and cells. The potential applications of HiP-CT were demonstrated through quantification and morphometry of glomeruli in an intact human kidney, and identification of regional changes to the architecture of the air-tissue interface and alveolar morphology in the lung of a deceased COVID-19 patient. Overall, we show that HiP-CT is a powerful tool which can provide a comprehensive picture of structural information for whole intact human organs, encompassing precise details on functional units and their constituent cells to better understand human health and disease.

Here we present the specifications and capabilities of the SYRMEP (SYnchrotron Radiation for MEdical Physics) beamline of the Italian Synchrotron “Elettra” in Trieste. SYRMEP was designed to provide X-ray imaging in an energy range that fits both biomedical research and clinical applications on patients. Additionally, SYRMEP covers a spatial resolution range of 100 μm down to 1 μm (1/50th the width of a human hair) with a comparably wide field-of-view (FOV), which enables studies in large specimens and therefore closes the gap between micro computed tomography (CT) in biomedical research and clinical CT imaging. Moreover, the possible long sample-to-detector distance allows for an effective use of free-propagation phase contrast that increases dose efficacy and soft-tissue contrast. These parameters and their function are further discussed on a set of examples of biomedical applications.

Fibrosis represents a relevant response to the implantation of biomaterials, which occurs not only at the tissue-material interface (fibrotic encapsulation) but also within the void fraction of complex three-dimensional (3D) biomaterial constructions (fibrotic ingrowth). Usual evaluation of the biocompatibility mostly depicts fibrosis at the interface of the biomaterial using semiquantitative scores. Here, the relations between encapsulation and infiltrating fibrotic growth are poorly represented. Virtual pathology and digital image analysis provide new strategies to assess fibrosis in a more differentiated way. In this study, we adopted a method previously used to quantify fibrosis in visceral organs to the quantification of fibrosis to 3D biomaterials. In a proof-of-concept study, we transferred the "Collagen Proportionate Area" (CPA) analysis from hepatology to the field of biomaterials. As one task of an experimental animal study, we used CPA analysis to quantify the fibrotic ingrowth into a filamentous scaffold after subcutaneous implantation. We were able to demonstrate that the application of the CPA analysis is well suited as an additional fibrosis evaluation strategy for new biomaterial constructions. The CPA method can contribute to a better understanding of the fibrotic interactions between 3D scaffolds and the host tissue responses.

Various lung diseases, including pulmonary hypertension, chronic obstructive pulmonary disease or bronchopulmonary dysplasia, are associated with structural and architectural alterations of the pulmonary vasculature. The light microscopic (LM) analysis of the blood vessels is limited by the fact that it is impossible to identify which generation of the arterial tree an arterial profile within a LM microscopic section belongs to. Therefore, we established a workflow that allows for the generation-specific quantitative (stereological) analysis of pulmonary blood vessels. A whole left rabbit lung was fixed by vascular perfusion, embedded in glycol methacrylate and imaged by micro-computed tomography (µCT). The lung was then exhaustively sectioned and 20 consecutive sections were collected every 100 µm to obtain a systematic uniform random sample of the whole lung. The digital processing involved segmentation of the arterial tree, generation analysis, registration of LM sections with the µCT data as well as registration of the segmentation and the LM images. The present study demonstrates that it is feasible to identify arterial profiles according to their generation based on a generation-specific color code. Stereological analysis for the first three arterial generations of the monopodial branching of the vasculature included volume fraction, total volume, lumen-to-wall ratio and wall thickness for each arterial generation. In conclusion, the correlative image analysis of µCT and LM-based datasets is an innovative method to assess the pulmonary vasculature quantitatively. ispartof: HISTOCHEMISTRY AND CELL BIOLOGY vol:155 issue:2 pages:227-239 ispartof: location:Germany status: published

Objectives To investigate the value of spectral-detector computed tomography (SDCT) parameters for the quantitative differentiation between atelectasis and pneumonia on contrast-enhanced chest CT. Material and methods Sixty-three patients, 22 clinically diagnosed with pneumonia and 41 with atelectasis, underwent contrast-enhanced SDCT scans during the venous phase. CT numbers (Hounsfield Units [HU]) were measured on conventional reconstructions (CON120kVp) and the iodine concentration (Ciodine, [mg/ml]), and effective atomic number (Zeff) on spectral reconstructions, using region-of-interest (ROI) analysis. Receiver operating characteristics (ROC) and contrast-to-noise ratios (CNRs) were calculated to assess each reconstruction's potential to differentiate between atelectasis and pneumonia. Results On contrast-enhanced SDCT, the difference between atelectasis and pneumonia was significant on CON120kVp, Ciodine, and Zeff images (p < 0.001). On CON120kVp images, a threshold of 81 HU achieved a sensitivity of 93 % and a specificity of 95 % for identifying pneumonia, while Ciodine and Zeff images reached the same sensitivity but lower specificities of 85 % and 83 %. CON120kVp images showed significantly higher CNRs between normal lung and atelectasis or pneumonia with 30.63 and 27.69 compared to Ciodine images with 3.54 and 1.27 and Zeff images with 4.22 and 7.63 (p < 0.001). None of the parameters could differentiate atelectasis and pneumonia without contrast media. Conclusions Contrast-enhanced SDCT can differentiate atelectasis and pneumonia based on the spectral parameters Ciodine, and Zeff. However, they had no added value compared to CT number measurement on CON120kVp images. Furthermore, contrast media is still needed for a differentiation based on quantitative SDCT parameters., Highlights • Spectral CT parameters Ciodine and Zeff can differentiate atelectasis from pneumonia on contrast-enhanced images. • Spectral CT parameters Ciodine and Zeff have no added value compared to CT number measurement on CON120kVp images. • CNRs between normal and consolidated lung were higher on conventional on spectral images., Pneumonia, Atelectasis, Diagnosis, SDCT

In this report, we investigated the physical conditions for creating pectin polymer-polymer (homopolymer) entanglement. The potential role of water movement in creating pectin entanglement was investigated by placing water droplets-equivalent to the water content of two gel phase films-between two glass phase films and compressing the films at variable probe velocities. Slow probe velocity (0.5 mm/sec) demonstrated no significant debonding. Corresponding videomicroscopy demonstrated an occasional water bridge, but no evidence of stranding or polymer entanglement. In contrast, fast probe velocity (5 mm/sec) resulted in 1) an increase in peak adhesion strength, 2) a progressive debonding curve, and 3) increased work of cohesion (p

BACKGROUND: The histomorphological changes of lung damage in severe coronavirus disease 2019 (COVID-19) have not yet been adequately characterized. In this article, we describe the sequence of pathological changes in COVID-19 and discuss the implications for approaches to treatment. METHODS: Standardized autopsies were performed on thirteen patients who had died of COVID-19. The findings were analyzed together with clinical data from the patients’ medical records. RESULTS: Most (77%) of the deceased patients were men. Their median age at death was 78 years (range, 41–90). Most of them had major pre-existing chronic diseases, most commonly arterial hypertension. The autopsies revealed characteristic COVID-19-induced pathological changes in the lungs, which were regarded as the cause of death in most patients. The main histological finding was sequential alveolar damage, apparently due in large measure to focal capillary microthrombus formation. Alveolar damage leads to the death of the patient either directly or by the induction of pulmonary parenchymal fibrosis. Diffuse lung damage was seen exclusively in invasively ventilated patients. CONCLUSION: Autopsies are crucial for the systematic assessment of new diseases such as COVID-19: they provide a basis for further investigations of disease mechanisms and for the devising of potentially effective modes of treatment. The autopsy findings suggest that focal damage of the microvascular pulmonary circulation is a main mechanism of lethal lung disease due to the SARS-CoV-2 virus. It may also be a cause of persistent lung damage in patients who recover from severe COVID-19.

Aim Light microscopy is used as template in the evaluation and further development of medical imaging methods. Tissue shrinkage caused by histological processing is known to influence lung tissue dimensions. In diagnosis of COPD, computed tomography (CT) is widely used for automated airway measurement. The aim of this study was to compare histological and computed tomographic measurements of pig lung bronchi. Methods Airway measurements of pig lungs were performed after freezing under controlled inflation pressure in a liquid nitrogen bath. The wall thickness of seven bronchi was measured via Micro-CT and CT using the integral-based method (IBM) and the full-width-at-half-maximum method (FWHM) automatically and histologically on frozen and paraffin sections. Statistical analysis was performed using the Wilcoxon test, Pearson's correlation coefficient with a significance level at p, Automated measurement techniques advance diagnosis of lung diseases. Pig bronchi wall size varies between Micro-CT, CT IBM, CT FWHM and histology. CT IBM is closest to histological results, followed by Micro-CT. CT FWHM differs highly from all other groups. https://bit.ly/3iRXSrv

Lung regeneration occurs in a variety of adult mammals after surgical removal of one lung (pneumonectomy). Previous studies of murine post-pneumonectomy lung growth have identified regenerative “hotspots” in subpleural alveolar ducts; however, the cell-types participating in this process remain unclear. To identify the single cells participating in post-pneumonectomy lung growth, we used laser microdissection, enzymatic digestion and microfluidic isolation. Single-cell transcriptional analysis of the murine alveolar duct cells was performed using the C1 integrated fluidic circuit (Fluidigm) and a custom PCR panel designed for lung growth and repair genes. The multi-dimensional data set was analyzed using visualization software based on the tSNE algorithm. The analysis identified 6 cell clusters; 1 cell cluster was present only after pneumonectomy. This post-pneumonectomy cluster was significantly less transcriptionally active than 3 other clusters and may represent a transitional cell population. A provisional cluster identity for 4 of the 6 cell clusters was obtained by embedding bulk transcriptional data into the tSNE analysis. The transcriptional pattern of the 6 clusters was further analyzed for genes associated with lung repair, matrix production, and angiogenesis. The data demonstrated that multiple cell-types (clusters) transcribed genes linked to these basic functions. We conclude that the coordinated gene expression across multiple cell clusters is likely a response to a shared regenerative microenvironment within the subpleural alveolar ducts.

Biodegradable pectin polymers have been recommended for a variety of biomedical applications, ranging from the delivery of oral drugs to the repair of injured visceral organs. A promising approach to regulate pectin biostability is the blending of pectin films. To investigate the development of conjoined films, we examined the physical properties of high-methoxyl pectin polymer-polymer (homopolymer) interactions at the adhesive interface. Pectin polymers were tested in glass phase (10&ndash, 13% w/w water content) and gel phase (38&ndash, 41% w/w water content). The tensile strength of polymer-polymer adhesion was measured after variable development time and compressive force. Regardless of pretest parameters, the adhesive strength of two glass phase films was negligible. In contrast, adhesion testing of two gel phase films resulted in significant tensile adhesion strength (p &lt, 0.01). Adhesion was also observed between glass phase and gel phase films&mdash, likely reflecting the diffusion of water from the gel phase to the glass phase films. In studies of the interaction between two gel phase films, the polymer-polymer adhesive strength increased linearly with increasing compressive force (range 10&ndash, 80 N) (R2 = 0.956). In contrast, adhesive strength increased logarithmically with time (range 10&ndash, 10,000 s) (R2 = 0.913), most of the adhesive strength was observed within minutes of contact. Fracture mechanics demonstrated that the adhesion of two gel phase films resulted in a conjoined film with distinctive physical properties including increased extensibility, decreased stiffness and a 30% increase in the work of cohesion relative to native polymers (p &lt, 0.01). Scanning electron microscopy of the conjoined films demonstrated cross-grain adhesion at the interface between the adhesive homopolymers. These structural and functional data suggest that blended pectin films have emergent physical properties resulting from the cross-grain intermingling of interfacial pectin chains.

In-line free propagation phase-contrast synchrotron tomography of the lungs has been shown to provide superior image quality compared with attenuation-based computed tomography (CT) in small-animal studies. The present study was performed to prove the applicability on a human-patient scale using a chest phantom with ventilated fresh porcine lungs. Local areas of interest were imaged with a pixel size of 100 µm, yielding a high-resolution depiction of anatomical hallmarks of healthy lungs and artificial lung nodules. Details like fine spiculations into surrounding alveolar spaces were shown on a micrometre scale. Minor differences in artificial lung nodule density were detected by phase retrieval. Since we only applied a fraction of the X-ray dose used for clinical high-resolution CT scans, it is believed that this approach may become applicable to the detailed assessment of focal lung lesions in patients in the future.

Bronchial thermoplasty (BT) can be considered in the treatment of severe asthma to reduce airway smooth muscle mass and bronchoconstriction. We hypothesized that BT may thus have long-term effects on airway dimensions and air-trapping detectable by quantitative computed tomography (QCT).Paired in- and expiratory CT and inspiratory CT were acquired in 17 patients with severe asthma before and up to two years after bronchial thermoplasty and in 11 additional conservatively treated patients with serve asthma, respectively. A fully automatic software calculated the airways metrics for wall thickness (WT), wall percentage (WP), lumen area (LA) and total diameter (TD). Furthermore, lung air-trapping was quantified by determining the quotient of mean lung attenuation in expiration vs. inspiration (E/I MLA) and relative volume change in the Hounsfield interval -950 to -856 in expiration to inspiration (RVCBT reduced WT for the combined analysis of the 2nd-7th airway generation significantly by 0.06 mm (p = 0.026) and WP by 2.05% (p 0.001), whereas LA and TD did not change significantly (p = 0.147, p = 0.706). No significant changes were found in the control group. Furthermore, E/I MLA and RVCBT significantly reduced airway narrowing and air-trapping in patients with severe asthma. This can be interpreted as direct therapeutic effects caused by a reduction in airway-smooth muscle mass and changes in innervation. A reduction in air-trapping indicates an influence on more peripheral airways not directly treated by the BT procedure.

Pulmonary "air leaks," typically the result of pleural injury caused by lung surgery or chest trauma, result in the accumulation of air in the pleural space (pneumothorax). Air leaks are a major source of morbidity and prolonged hospitalization after pulmonary surgery. Previous work has demonstrated structural heteropolysaccharide (pectin) binding to the mouse pleural glycocalyx. The similar lectin-binding characteristics and ultrastructural features of the human and mouse pleural glycocalyx suggested the potential application of these polymers in humans. To investigate the utility of pectin-based polymers, we developed a simulacrum using freshly obtained human pleura. Pressure-decay leak testing was performed with an inflation maneuver that involved a 3 s ramp to a 3 s plateau pressure; the inflation was completely abrogated after needle perforation of the pleura. Using nonbiologic materials, pressure-decay leak testing demonstrated an exponential decay with a plateau phase in materials with a Young's modulus less than 5. In human pleural testing, the simulacrum was used to test the sealant function of four mixtures of pectin-based polymers. A 50% high-methoxyl pectin and 50% carboxymethylcellulose mixture demonstrated no sealant failures at transpleural pressures of 60 cmH2 O. In contrast, pectin mixtures containing 50% low-methoxyl pectin, 50% amidated low-methoxyl pectins, or 100% carboxymethylcellulose demonstrated frequent sealant failures at transpleural pressures of 40-50 cmH2 O (p