Volumetric atlasing in the rodent brain: connecting experimental image data to standard anatomical space

Abstract

A major challenge for understanding the brain in health and disease is related to combining information about the brain from many different sources. Spatial analysis and comparison of 2D and 3D brain images with the aim to discover new structural and functional features in the data requires mapping the images to a common anatomical space. For rodent models, widely used anatomical reference atlases have until recently been published in a book format that hinders effective comparison across images acquired at different angles and dimensions. The ambition of this study is to advance digital atlasing of the rodent brain towards a new generation of volumetric atlases that facilitate integration of whole-brain image data from multiple modalities. We present the first comprehensive anatomical reference atlas of the Sprague Dawley rat brain based on magnetic resonance imaging. To ensure interoperability with other atlases, we applied the Waxholm Space standard in the rat brain for the first time, and created a mapping against the widely used stereotaxic space. For connecting experimental data to the new reference atlas, we established standard anatomical landmarks for image registration across different levels of structural detail, and created a workflow for section to volume alignment and spatial analysis of brain-wide microscopic image series. Open access to the results of this work has enabled localization of signal in functional and structural image volumes, integration of 2D image series, and development of new atlases of various features of the brain.