Tissue optical clearing methods for microscopy: A review of their application in neuroscience

Abstract

Recent advances in microscopy have enabled cellular-resolution imaging of thick tissue samples or even whole organs. The natural opacity of organs and tissues acts as a barrier to light penetration and must be removed to visualise structures of interest on a three-dimensional scale. Tissue optical clearing methods achieve sample transparency while also preserving fluorescently labelled epitopes. This innovative approach to sample preparation effectively enhances traditional histological sections and, with the aid of light sheet microscopy, enables optical sectioning and three-dimensional reconstruction of entire organs, even whole brains. Light sheet microscopy of optically cleared brain samples is a valuable method in neuroscience that is used in neuro-oncology, traumatic brain injury, ischemic brain injury, and neurodegenerative disease research.
In this review, we describe tissue optical clearing methods used to achieve optical transparency in brain samples. This quickly developing field has a significant potential for producing cutting-edge uses in neuroscience research.