AUTHOR=Willekens Stefanie M. A. , Morini Federico , Mediavilla Tomas , Nilsson Emma , Orädd Greger , Hahn Max , Chotiwan Nunya , Visa Montse , Berggren Per-Olof , Ilegems Erwin , Överby Anna K. , Ahlgren Ulf , Marcellino Daniel 

TITLE=An MR-based brain template and atlas for optical projection tomography and light sheet fluorescence microscopy in neuroscience

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 18 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2024.1328815

DOI=10.3389/fnins.2024.1328815

ISSN=1662-453X

ABSTRACT=Optical Projection Tomography (OPT) and light sheet fluorescence microscopy (LSFM) are highresolution optical imaging techniques, ideally suited for ex vivo 3D whole mouse brain imaging. Although they exhibit high specificity for their targets, the anatomical detail provided by tissue autofluorescence remains limited. The possibility to anatomically map optical 3D signals by creating fusion images with magnetic resonance (MR) images, widely used in clinical and preclinical neuroimaging, would greatly benefit the application of optical mouse brain imaging in neuroscience. Therefore, we developed a novel MR-based brain template and atlas, specifically designed for optically cleared brains. We investigated the effect of tissue preprocessing and clearing on brain size and morphology and optimized the template for BABB/Murray´s clear and DBE/iDISCO. Finally, we created fluorescence-template fusion images allowing detailed anatomical brain mapping of 3D optical signals. Using this approach, we identified virus infected brain regions, mapped dopamine transporter and translocator protein expression and, traced innervation from the eye along the optic tract to the thalamus and superior colliculus using cholera toxin B. Taken together, these specific MR brain templates for optically cleared brains enable a broad range of neuroscientific applications integrating 3D optical brain imaging.