@article {Battistella2022.03.22.485275, author = {Eliana Battistella and Jan Schniete and Katrina Wesencraft and Juan Quintana and Gail McConnell}, title = {Light-sheet mesoscopy with the Mesolens provides fast sub-cellular resolution imaging throughout large tissue volumes}, elocation-id = {2022.03.22.485275}, year = {2022}, doi = {10.1101/2022.03.22.485275}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Rapid imaging of large biological tissue specimens such as ultrathick sections of mouse brain cannot easily be performed with a standard microscope. Optical mesoscopy offers a solution, but thus far imaging has been too slow to be useful for routine use. We have developed two different illuminators for light-sheet mesoscopy with the Mesolens and we demonstrate their use in high-speed optical mesoscale imaging of large tissue specimens. The first light-sheet approach uses Gaussian optics and is straightforward to implement. It provides excellent lateral resolution and high-speed imaging, but the axial resolution is poor. The second light-sheet is a more complex Airy light-sheet that provides sub-cellular resolution in three dimensions that is comparable in quality to point-scanning confocal mesoscopy, but the light-sheet method of illuminating the specimen reduces the imaging time by a factor of 14. This creates new possibilities for high-content, higher-throughput optical bioimaging at the mesoscale.Competing Interest StatementThe authors have declared no competing interest.}, URL = {https://www.biorxiv.org/content/early/2022/03/22/2022.03.22.485275}, eprint = {https://www.biorxiv.org/content/early/2022/03/22/2022.03.22.485275.full.pdf}, journal = {bioRxiv} }