Computational conjugate adaptive optics for longitudinal through-skull imaging of cortical myelin

We present a 1.3-μm reflection matrix microscope and computational conjugate adaptive optics algorithm for label-free longitudinal imaging of cortical myelin through an intact mouse skull. The myelination processes of the same mice were observed from 3 to 10 postnatal weeks down to cortical layer 4 with a near-diffraction-limited resolution of 0.79 µm. Our system will expedite the investigations on the role of myelination in learning, memory, and brain disorders.