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.

Highlights

  • Recent developments in sample preparation and microscopy have opened the door for high-resolution whole brain imaging in small mammals such as mice

  • The second group of methods used to acquire whole-brain fluorescence microscopy images is the combination of optical tissue clearing and light-sheet fluorescence microscopy (LSFM)

  • This review will focus on published tools that are freely available to the community, and which could be adopted by a typical laboratory without any high-performance computing resources. When it comes to analysing whole-brain microscopy datasets, one of the first challenges is segmenting the features of interest

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Summary

Traditional methods

Imaging of large intact brains has been possible for many decades, for example using ultrasound (Donald et al, 1958), computed tomography (Hounsfield, 1973), or magnetic resonance imaging (MRI, Lauterbur, 1973) These traditional three-dimensional imaging methods benefit from being noninvasive, and many aspects of brain activity and its structure can be studied. They have two main limitations when it comes to studying detailed organisation They have relatively low spatial resolution which, continuing to improve, is limited to measurements of gross brain anatomy. These methods do not have the specificity required to study all aspects of neuroanatomy using cutting edge viral, genetic and immunofluorescence toolkits

Whole-brain fluorescence microscopy
Image analysis
Neuronal somata
Neuronal morphology
Connectivity mapping
Vasculature
Brain registration and segmentation
Image Registration
Segmentation
Atlas reference images
Alternative atlas formats
Choosing an atlas
Raw data
Segmented data
Additional analyses
Tool comparison
Neuronal somata detection
Registration and segmentation
Workflow integration
Common file formats
Common software packages
Plugin systems
Communication and collaboration
Conclusions
Full Text
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