3 D virtual Histopathology of Cardiac 1 Tissue from Covid-19 Patients based 2 on Phase-Contrast X-ray Tomography

14 We have used phase-contrast X-ray tomography to characterize the three-dimensional (3d) 15 structure of cardiac tissue from patients who succumbed to Covid-19. By extending conventional 16 histopathological examination by a third dimension, the delicate pathological changes of the 17 vascular system of severe Covid-19 progressions can be analyzed, fully quantified and compared to 18 other types of viral myocarditis and controls. To this end, cardiac samples with a cross section of 19 3.5mm were scanned at a laboratory setup as well as at a parallel beam setup at a synchrotron 20 radiation facility. The vascular network was segmented by a deep learning architecture suitable for 21 3d datasets (V-net), trained by sparse manual annotations. Pathological alterations of vessels, 22 concerning the variation of diameters and the amount of small holes, were observed, indicative of 23 elevated occurrence of intussusceptive angiogenesis, also confirmed by high resolution cone beam 24 X-ray tomography and scanning electron microscopy. Furthermore, we implemented a fully 25 automated analysis of the tissue structure in form of shape measures based on the structure 26 tensor. The corresponding distributions show that the histopathology of Covid-19 differs from both 27 influenza and typical coxsackie virus myocarditis. 28