LSFM (or “LightSheet Fluorescence Microscopy”) is the technology of choice for fast 3D imaging of thick samples.
The LSFM technology relies on the fact that a single thin plane (optical section), and only that plane, is illuminated by excitation light. The light emitted by this entire plane is then collected through objectives perpendicular to the excitation axis and can be captured on the sensor of a camera (rather than pixel by pixel as in confocal microscopy or laser scanning approaches). The consecutive acquisition of several parallel focal planes makes it possible to quickly generate 3D reconstructions of entire samples, with limitted photobleaching and phototoxicity. More informations about LSM technology and Lightsheet.z1 here.
To achieve deep imaging of naturally opaque organs, tissue optical clearing methods have been developed (and are still under active development). For more information about tissue optical clearing:
Richardson et Lichtman - Clarifying tissue clearing (Cell 2015, 162 (2): 256-257)
Matryba, Kaczmarek et Golab - Advances in Ex Tissue Optical Clearing (Laser Photonics Rev 2019, 13: 1800292)
Imaging options using the lightsheet configuration of 2IP: