Isotropic three-dimensional imaging with lattice light-sheet difference microscopy

Through the interference of several beams with the same phase at the rear pupil, an optical lattice is generated and used as the excitation light field in lattice light-sheet microscopy (LLSM). Although, LLSM offers fast imaging ability through the dithered mode, it suffers from poor axial resolution. On the other hand, the structured illumination microscopy (SIM) mode in LLSM provides a high but anisotropic spatial resolution at the price of a lower imaging speed. In this Letter, we propose a new, to the best of our knowledge, type of optical lattice by defining the composed beam vectors with different phases. The lattice light-sheet difference microscopy (LLSDM) proposed in this work utilizes the new optical lattice along with the conventional one by simply changing the pattern loaded on the spatial light modulator. Through simulations with parameters obtained from the real acquisition procedures and the microscope properties, we examine the feasibility of LLSDM, and obtain nearly isotropic spatial resolution and great alleviation of the sidelobes. These characteristics enable LLSDM to broaden the accessible imaging content of light-sheet microscopes and further facilitate their applications in life sciences. (C) 2020 Optical Society of America.