Mesoscale microscopy and image analysis tools for understanding the brain

Abstract

Over the last ten years, developments in whole-brain microscopy now allow for high-resolution imaging of intact brains of small animals such as mice. These complex images contain a wealth of information, but many neuroscience laboratories do not have all of the computational knowledge and tools needed to process these data. We review recent open source tools for registration of images to atlases, and the segmentation, visualisation and analysis of brain regions and labelled structures such as neurons. Since the field lacks fully integrated analysis pipelines for all types of whole-brain microscopy analysis, we propose a pathway for tool developers to work together to meet this challenge.

Keywords: Image registration; Neuroscience; Segmentation; Visualisation; whole Brain microscopy.

Fig. 1

Warping to atlas space. Cells detected with cellfinder (Tyson et al., 2021a) from two rabies viral tracing experiments (red and blue), warped to the Allen Mouse Brain Common Coordinate Framework version 3 and visualised using brainrender (Claudi et al., 2021).

Fig. 2

Atlas-based segmentation. Atlas reference image (top left) and raw data (top right) are filtered, and the reference image is mapped onto the raw data. Other images, such as the atlas annotations and the brain hemispheres can then be warped similarly onto the raw data.

Fig. 3

Comparison of mouse atlases. Single hemisphere section at bregma. A) Allen Mouse Brain Common Coordinate Framework version 3 (Wang et al., 2020). B) Enhanced and Unified Mouse Brain Atlas (Chon et al., 2019). C) Molecular atlas of the adult mouse brain (Ortiz et al., 2020).