Modern microscopy makes many modalities available to the biological investigator, but selection of the appropriate techniques is important. Light microscopy such as phase and differential phase contrast enable label-free studies of individual and bulk cells such as MSCs, and how, as they differentiate, the deposited mineral can be quantified and analysed computationally. We present a robust, user friendly phase imaging system that can be operated by any lab user to investigate translucent samples without the need to understand how the imaging technique works. Multi-photon microscopy enables high resolutionimaging within thick tissues using fluorescence or other physical phenomena such as second harmonic generation (SHG). These non-linear modalities are particularly susceptible to optical aberrations present within the sample. We recover high resolution imaging by means of a high spatial frequency digital micromirror (DMD), and binary wavefront modulation. A genetic algorithm optimizes the pattern by evaluating the intensity ofthe intrinsic SHG point spread function in the living bone. We present a near eight-fold intensity and 62.5% spatial frequency improvement in vivo while recording mitochondrial dynamics within a bone cavity approximately 120µm below the surface of the skull. Further improvements to high-order aberrations are investigated by decreasing the correction time, analyzing the impact of sparsity of DMD elements and by combining low- and high-order aberration correction to further improvement depth of penetration in living bone tissue. NIR illumination of biological tissue enables deeper penetration and further reduction of the focal volume and by combining this 3-photon emission with image scanning microscopy (ISM) to image beyond the diffraction limit, we envision high resolution imaging within living skull to elucidate the underlying mechanisms of osteogenesis.