RT Journal Article SR Electronic T1 3D super-resolution deep-tissue imaging in living mice JF bioRxiv FD Cold Spring Harbor Laboratory SP 790212 DO 10.1101/790212 A1 Mary Grace M. Velasco A1 Mengyang Zhang A1 Jacopo Antonello A1 Peng Yuan A1 Edward S. Allgeyer A1 Dennis May A1 Ons M’Saad A1 Phylicia Kidd A1 Andrew E. S. Barentine A1 Valentina Greco A1 Jaime Grutzendler A1 Martin J. Booth A1 Joerg Bewersdorf YR 2019 UL http://biorxiv.org/content/early/2019/10/02/790212.abstract AB Stimulated emission depletion (STED) microscopy enables the three-dimensional (3D) visualization of dynamic nanoscale structures in living cells, offering unique insights into their organization. However, 3D-STED imaging deep inside biological tissue is obstructed by optical aberrations and light scattering. We present a STED system that overcomes these challenges. Through the combination of 2-photon excitation, adaptive optics, far-red emitting organic dyes, and a long-working distance water-immersion objective lens, our system achieves aberration-corrected 3D super-resolution imaging, which we demonstrate 164 µm deep in fixed mouse brain tissue and 76 µm deep in the brain of a living mouse.