Multiscale 3-dimensional pathology findings of COVID-19 diseased lung using high-resolution cleared tissue microscopy

Guang Li; Sharon E. Fox; Brian Summa; Carola Wenk; Aibek Akmatbekov; Jack L. Harbert; Richard S. Vander Heide; J. Quincy Brown

Taken together, these findings support the role of 3-dimensional imaging of cleared tissues for the study of COVID-19 histopathology. The technological approach used here follows that described previously by our group and others. [4] [5] [6] [7] [8] [9] 11, 13 The specific fluorescence contrast scheme used here to replicate H&E, 7 like similar schemes reported previously, 4-6 has been shown repeatedly to provide reliable and accurate analogs to traditional H&E contrast in fluorescence microscopy. While our images were collected with a specific variant of light sheet microscopy, similar images could be obtained at varying levels of throughput with other optical sectioning microscopes. This approach will not likely soon replace traditional 2D histopathology due to its relative complexity and the size of the data generated -for a single sample from a single patient, we generated images nearing 1 teravoxel in size and exceeding 1.5 TB of processed data for the sample. However, it could serve as a useful adjunct to traditional histopathology, as shown here. In particular, as the figures and supplemental videos show, inspection of the 3D data provides a more comprehensive and intuitive understanding of the changes due to disease. While this report is limited to a single sample from a single patient, the utility of the findings support continued study on tissues from multiple organs from a wider cohort of patients, and with the addition of specific molecular markers, which is the subject of ongoing work.