Increasing the resolution of light sheet microscopy in the presence of aberrations

Single plane illumination microscopy (SPIM) allows rapid imaging of large, three-dimensional, samples of living tissue. The thin light sheet ensures high contrast whilst photo-bleaching and damage are kept to a minimum. However, many specimen of interest have a significant thickness. To date, high axial resolution in such specimen has only been achieved by compromising these key advantages and adding considerable technical complexity. Although the light sheet can propagate several hundreds of micrometers into the tissue, its width can be several orders of magnitude larger than it would be in a homogeneous sample. In this paper we explore the use of pupil-phase modulation to overcome such sample-induced aberrations and produce diffraction-limited deep inside turbid samples.