The combination of light-sheet fluorescent microscopy (LSFM), whole organ immunolabelling and advanced image analysis is currently revolutionizing the approach to studying neurological diseases in preclinical animal models. Today, it is possible to visualize a single cell in intact mouse brain. In combination with AI and deep learning algorithms information on specific endpoints such as signal intensities, cell counts, volumes, densities, and branching can be quantified. Thus, it is possible to precisely measure endpoints such as neuronal activity (c-Fos), BBB passage, viral or non-viral gene delivery or pathologies such as plaques or alpha synuclein at a whole brain level.