Super-resolution in-vivo retinal imaging using structured illumination ophthalmoscopy

Super-resolution optical microscopy has allowed the observation of multiple mechanisms with unprecedented resolution in physics, chemistry and biology. Although structured illumination microscopy (SIM) is one of the most versatile super-resolution techniques, its application to live imaging has been so far mainly limited to fluorescent and stationary specimens. Here, we present advancements in SIM to jointly tackle all the challenges of imaging living samples, i.e., obtaining super-resolution over an undistorted wide-field while dealing with sample motion, scattering, sample-induced optical aberrations and low signal-to-noise ratio. By using adaptive optics to compensate for optical aberrations and a reconstruction algorithm tailored for a moving and thick tissue, we successfully applied super-resolution SIM to in-vivo retinal imaging. Our reconstruction method exploits the sample motion to obtain the diversity required by SIM, thus turning an inconvenience into an asset. We demonstrate structured illumination ophthalmoscopy for high contrast super-resolution in-vivo imaging of the human retina.