Development of brain templates for whole brain atlases

In neuroscience, Brain template images and annotation atlases are key to analyzing whole brain microscopy images in a common coordinate framework (CCF) and sharing of anatomical data among neuroscientists. Mapping individual animal specimen brain to a common space allows neuroscientists compare and utilize data from experiments done on other modalities or markers. With the advent of new clearing and novel light microscopy techniques, large number of samples are imaged in these unique combinations of clearing and microscopy that the experimenter deems best to bring out the best signal-to-noise ratio for their biological data. This paper describes our framework that each such experimenter to create a template brain registered with the Allen CCF for their unique combination. Further, we demonstrate the ability of the framework to create a template brain for an enhanced delipidation protocol called UClear [Unpublished] and imaged using LaVision BioTech Ultramicroscope II. The cleared brains were imaged in dibenzyl ether (DBE) under 488-nm illumination conditions that allowed the visualization of major brain regions based on intrinsic tissue autofluorescence. As contrast in these images differs from brains imaged by serial two-photon tomography used to generate the CCF space of the Allen Mouse Brain Atlas, we developed a new CCF brain template for processing and analysis of the UClear brains. This brain template generation method can make the registration pipeline agnostic to the tissue clearing and imaging protocol.