Biobeam—Multiplexed wave-optical simulations of light-sheet microscopy

Sample-induced image-degradation remains an intricate wave-optical problem in light-sheet microscopy. Here we present biobeam, an open-source software package that enables simulation of operational light-sheet microscopes by combining data from 105–106 multiplexed and GPU-accelerated point-spread-function calculations. The wave-optical nature of these simulations leads to the faithful reproduction of spatially varying aberrations, diffraction artifacts, geometric image distortions, adaptive optics, and emergent wave-optical phenomena, and renders image-formation in light-sheet microscopy computationally tractable.Author summary: Modern microscopes permit to acquire high quality images of large fields of view, which is the result of a decade-long development of computer aided optical design. However, this high image quality can only be obtained at the very surface of biological specimens: when trying to penetrate deeper into biological tissues, light scattering by cells rapidly leads to severe image blur and computers have so far been unable to model the process by which light forms images in such turbid optical environments. We developed a software that allows one to simulate how microscopes record images deep inside scattering biological samples. Our software reproduces a wide range of optical effects that underlie image blur in tissues. Hence strategies to improve image quality within three-dimensional samples can now be systematically tested by computers. Specifically, our software reproduces intricate wave-optical effects that have recently been proposed as strategies to gain perfect images even in the most turbid environments.This provides the chance for a new generation of microscopes, in which computer models guide the imaging process to enable highest possible resolution even deep inside biological specimens.