Quantitative analysis of airway obstruction in lymphangioleiomyomatosis

Lymphangioleiomyomatosis (LAM) is a rare, cystic lung disease with progressive pulmonary function loss caused by progressively proliferating LAM cells. The degree of airway obstruction has not been well investigated within the pathogenesis of LAM. Using a combination of ex vivo computed tomography (CT), microCT and histology, the site and nature of airway obstruction in LAM explant lungs was compared with matched control lungs (n=5 each). The total number of airways per generation, total airway counts, terminal bronchioles number and surface density were compared in LAM versus control. Ex vivo CT analysis demonstrated a reduced number of airways from generation 7 on (p<0.0001) in LAM compar…

A multiscale X-ray phase-contrast tomography dataset of whole human left lung

ABSTRACTTechnological 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 tiss…

Plexiform Vasculopathy in Chronic Thromboembolic Pulmonary Hypertension

The bronchial circulation in COVID-19 pneumonia.

American journal of respiratory and critical care medicine : AJRCCM 205(1), 121-125 (2022). doi:10.1164/rccm.202103-0594IM

Multiscale three-dimensional imaging of intact human organs down to the cellular scale using hierarchical phase-contrast tomography

ABSTRACTHuman 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…

The Adult Sprague-Dawley Sugen-Hypoxia Rat Is Still "the One:" A Model of Group 1 Pulmonary Hypertension: Reply to Le Cras and Abman

To the editor: Kojonazarov et al. recently reported severe emphysema in the SU5416/Hypoxia (SuHx) rat model of pulmonary hypertension (1). The authors found that adult male Wistar Kyoto (WKY) rats had increased air-to-tissue ratio as judged by non-gated in vivo micro-computed tomography (CT), and an increased mean linear intercept (MLI) as surrogate of emphysema (1, 2). Le Cras and Abman now responded to the Kojonazarov report by underlining the “important role of the developmental timing of disrupted VEGF signaling” (3). They cite earlier studies conducted on the ovine fetus showing that VEGF inhibition caused vascular remodeling, reduction in vascular/airway growth, and neonatal pulmonary…

Morphomolecular motifs of pulmonary neoangiogenesis in interstitial lung diseases

The pathogenetic role of angiogenesis in interstitial lung diseases (ILDs) is controversial. This study represents the first investigation of the spatial complexity and molecular motifs of microvascular architecture in important subsets of human ILD. The aim of our study was to identify specific variants of neoangiogenesis in three common pulmonary injury patterns in human ILD.We performed comprehensive and compartment-specific analysis of 24 human lung explants with usual intersitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) and alveolar fibroelastosis (AFE) using histopathology, microvascular corrosion casting, micro-comupted tomography based volumetry and gene expression…

Molecular similarities and differences from human pulmonary fibrosis and corresponding mouse model: MALDI imaging mass spectrometry in comparative medicine

Animal models can reproduce some model-specific aspects of human diseases, but some animal models translate poorly or fail to translate to the corresponding human disease. Here, we develop a strategy to systematically compare human and mouse tissues, and conduct a proof-of-concept experiment to identify molecular similarities and differences using patients with idiopathic pulmonary fibrosis and a bleomycin-induced fibrosis mouse model. Our novel approach employs high-throughput tissue microarrays (TMAs) of humans and mice, high-resolution matrix-assisted laser desorption/ionization-Fourier transform-ion cyclotron resonance-mass spectrometry imaging (MALDI-FT-ICR-MSI) to spatially resolve ma…

3D virtual histopathology of cardiac tissue from Covid-19 patients based on phase-contrast X-ray tomography

eLife 10, e71359 (2021). doi:10.7554/eLife.71359

Patterns of Carbon-Bound Exogenous Compounds in Patients with Lung Cancer and Association with Disease Pathophysiology.

Abstract Asymptomatic anthracosis is the accumulation of black carbon particles in adult human lungs. It is a common occurrence, but the pathophysiologic significance of anthracosis is debatable. Using in situ high mass resolution matrix-assisted laser desorption/ionization (MALDI) fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometry imaging analysis, we discovered noxious carbon-bound exogenous compounds, such as polycyclic aromatic hydrocarbons (PAH), tobacco-specific nitrosamines, or aromatic amines, in a series of 330 patients with lung cancer in highly variable and unique patterns. The characteristic nature of carbon-bound exogenous compounds had a strong association wi…

Angiogenesis Patterns in Interstitial Lung Disease

Comprehensive three‐dimensional morphology of neoangiogenesis in pulmonary veno‐occlusive disease and pulmonary capillary hemangiomatosis

Abstract 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 struc…

Visualization of SARS-CoV-2 in the Lung.

Microvascular placental alterations in maternal COVID-19

Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19

Abstract: BackgroundProgressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (Covid-19) pandemic. Despite widespread interest in the pathophysiology of the disease, relatively little is known about the associated morphologic and molecular changes in the peripheral lung of patients who die from Covid-19. MethodsWe examined 7 lungs obtained during autopsy from patients who died from Covid-19 and compared them with 7 lungs obtained during autopsy from patients who died from acute respiratory distress syndrome (ARDS) secondary to influenza A(H1N1) infection and 10 age-matched, uninfected control lungs. The lungs were studied with the use of seven-color immun…

3D virtual Histopathology of Cardiac Tissue from Covid-19 Patients based on Phase-Contrast X-ray Tomography

X-ray phase-contrast tomography datasets of formalin fixed paraffin embedded unstained cardiac tissue from Covid-19 patients as well as from control tissue. For each group one overview scan of the entire biopsy (3.5mm cross section) from binning and stitching different tomograms (PB bin2, voxel size: 1.3&micro;m) as well as the respective laboratory data (LJ, voxel size: 2&micro;m, tissue masked) and a cone-beam zoom tomogram recorded with waveguide illumination (WG, voxel size: 159 nm) is uploaded. Further datasets can be provided on request. The data has been recorded at the institute for X-ray physics (G&ouml;ttingen, Germany) and DESY at the GINIX instrument, beamline P10 of the PETRAII…