AO compensates for tissue-induced distortions using correction element(s) in combination with either a wavefront sensor or image-based sensorless wavefront estimation methods. Wavefront sensor approaches include Shack–Hartmann wavefront sensors with autofluorescent or near-IR guide stars,14,15 coherence gated wavefront sensing,16 and image-based methods that use information from acquired images to estimate the wavefront distortions.17–21 Wavefront sensorless approaches usually estimate an initial error and through an iterative scheme converge to an optimized solution based on metrics, such as total fluorescence intensity for confocal and two-photon microscopy.22–24 In other microscopy modalities, metrics such as maximum intensity of the image (or a part of the image),25 the low-frequency spatial content of the image, the image sharpness,26–28 and the Fourier metric29 have been used. To generate a corrected wavefront in all cases, a compensating optical element or elements are required; most commonly deformable mirrors (DM) are used. The correction attainable by a single DM depends on its pitch, number and stroke of actuators, and surface form (segmented or continuous facesheet). This functional characteristic of DMs makes them act as high-pass filters that primarily correct lower order aberrations. For correction of spatially confined high-order aberrations in biological tissues like bone, other technologies such as spatial light modulators (SLMs) or digital micromirror devices (DMDs)30–32 could potentially assist. They often contain hundreds or thousands of segments, but may have other limitations in response time or correction magnitude.