RT Journal Article SR Electronic T1 Fast 3D Clear: A Fast, Aqueous, Reversible Three-Day Tissue Clearing Method for Adult and Embryonic Mouse Brain and Whole Body JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.06.25.449994 DO 10.1101/2021.06.25.449994 A1 Kosmidis, Stylianos A1 Negrean, Adrian A1 Dranovsky, Alex A1 Losonczy, Attila A1 Kandel, Eric R. YR 2021 UL http://biorxiv.org/content/early/2021/08/04/2021.06.25.449994.abstract AB To date, a variety of optical clearing methods have emerged that serve as powerful tools to study intact organs and neuronal circuits. Here we describe a newly developed, aqueous clearing protocol named “Fast 3D Clear”, which relies on tetrahydrofuran (THF) for tissue delipidation, and iohexol (Histodenz) for clearing, such that tissues can be imaged under immersion oil in light sheet imaging systems. Fast 3D Clear requires three days to achieve high transparency of adult and embryonic mouse tissues, while maintaining their anatomical integrity, and preserving a vast array of transgenic and viral/dye fluorophores, such as GCaMP3/6, tdTomato, Fast Blue, and IRF670. A unique advantage of Fast 3D Clear is its complete reversibility and thus compatibility with tissue sectioning and immunohistochemistry. Fast 3D Clear can be easily and quickly applied to a wide range of biomedical studies, thereby greatly facilitating the acquisition of high-resolution, two - and three -dimensional images.Competing Interest StatementAll the authors have filled for a provisional patent application.