Fourier domain intensity coupling for scattering correction (FOCUS)

We introduce Fourier-domain intensity coupling for scattering correction (FOCUS), a novel two-photon microscopy technique that uses intensity modulation on the Fourier plane via a DMD to overcome tissue scattering. Unlike adaptive optics, FOCUS leverages multi-beam interference and utilizes multiply scattered photons, enabling high-resolution, high-contrast imaging beyond 900 μm in the intact mouse brain and transcranial imaging through the adult mouse skull. This breakthrough achieves over 60-fold fluorescence enhancement, paving the way for practical, deep in vivo imaging across the entire intact cortex.