TY - JOUR TI - 3D virtual pathohistology of lung tissue from Covid-19 patients based on phase contrast X-ray tomography AU - Eckermann, Marina AU - Frohn, Jasper AU - Reichardt, Marius AU - Osterhoff, Markus AU - Sprung, Michael AU - Westermeier, Fabian AU - Tzankov, Alexandar AU - Werlein, Christopher AU - Kühnel, Mark AU - Jonigk, Danny AU - Salditt, Tim A2 - Zaidi, Mone A2 - Barton, Matthias A2 - Khan, Ashraf A2 - Shamsi, Kohkan VL - 9 PY - 2020 DA - 2020/08/20 SP - e60408 C1 - eLife 2020;9:e60408 DO - 10.7554/eLife.60408 UR - https://doi.org/10.7554/eLife.60408 AB - We present a three-dimensional (3D) approach for virtual histology and histopathology based on multi-scale phase contrast x-ray tomography, and use this to investigate the parenchymal architecture of unstained lung tissue from patients who succumbed to Covid-19. Based on this first proof-of-concept study, we propose multi-scale phase contrast x-ray tomography as a tool to unravel the pathophysiology of Covid-19, extending conventional histology by a third dimension and allowing for full quantification of tissue remodeling. By combining parallel and cone beam geometry, autopsy samples with a maximum cross section of 8 mm are scanned and reconstructed at a resolution and image quality, which allows for the segmentation of individual cells. Using the zoom capability of the cone beam geometry, regions-of-interest are reconstructed with a minimum voxel size of 167 nm. We exemplify the capability of this approach by 3D visualization of diffuse alveolar damage (DAD) with its prominent hyaline membrane formation, by mapping the 3D distribution and density of lymphocytes infiltrating the tissue, and by providing histograms of characteristic distances from tissue interior to the closest air compartment. KW - Covid-19 KW - lung tissue KW - x-ray KW - phase contrast KW - tomography KW - 3d histology JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -