Aperture interference and the volumetric resolution of light field fluorescence microscopy

Light field microscopy (LFM) is an emerging technique for volumetric fluorescence imaging, but widespread use is hampered by its poor spatial resolution. Using diffraction-based analysis we show how this degraded resolution arises because conventional LFM aims to sample four dimensions of the light field. By instead prioritizing 3D volumetric information over 4D sampling, we can optically interfere certain redundant angular samples to allow higher spatial resolution while maintaining enough angular information for depth discrimination. With this in mind, we design a number of aperture plane sampling schemes, characterize their frequency support and invertibility, and describe how their relative performance depends on the operating signal-to-noise regime. With simulations and a prototype, we demonstrate a time-sequential amplitude mask-based acquisition approach that outperforms conventional LFM in terms of both spatial resolution and axial field of view.