Multiphoton microscopy is an established technique for deep in vivo neuroimaging. However, the volume of the adult brain in most model organisms (e.g. mouse) is beyond the reach of high resolution optical imaging techniques, limiting the study of neurobiological questions in adulthood. Danionella, a genus closely related to zebrafish, which have smaller brains and lack ossification above the brain in adulthood have been introduced for in vivo studying of brain circuits in adult stages. Here, we present a quantitative comparison of optical accessibility within the Danionella dracula brain with two- and three-photon microscopy.