The imaging of large living specimens with high temporal and spatial resolution is one of the goals of Philip J. Keller and his research team at Janelia Research Campus of the Howard Hughes Medical Institute in Ashburn, Virginia (USA). For this purpose, Keller and his colleague Raghav K. Chhetri have developed a light sheet microscope which can image the sample simultaneously from four directions - with high speed and high spatial resolution.
At the heart of the so called „IsoView“ light sheet microscope are four identical arms (or optical paths) arranged orthogonally to one another, each of which can simultaneously illuminate the sample and image the emitted fluorescent light. To keep crosstalk between the excitation and detection as small as possible, the optical paths are separated either temporally, spatially, or spectrally from each other. The four images generated are then combined to produce a largely isotropic image with high resolution in all dimensions. To this end, Keller and his team wrote their own implementation of the Lucy-Richardson three-dimensional multiview deconvolution algorithm. In addition to the high spatial resolution of the combined images, this approach also enables a high temporal resolution so that changes in the sample can be recorded over time.