Comparative prospects of imaging methods for whole-brain mammalian connectomics

TL;DR

This paper compares electron microscopy and expansion light-sheet fluorescence microscopy techniques to evaluate their potential for whole-brain mammalian connectomics, aiding future project planning.

Contribution

It provides a quantitative comparison of imaging technologies for whole-brain connectomics, highlighting their capabilities and limitations.

Findings

EM techniques offer high resolution but are slower.

ExLSFM methods are faster but may have resolution limitations.

The analysis guides technology choice for future connectomics projects.

Abstract

Mammalian whole-brain connectomes are a foundational ingredient for holistic understanding of brains. Indeed, imaging connectomes at sufficient resolution to densely reconstruct cellular morphology and synapses represents a longstanding goal in neuroscience. Mouse connectomes could soon come within reach while human connectomes remain a more distant yet still worthy goal. Though the technologies needed to reconstruct whole-brain connectomes have not yet reached full maturity, they are advancing rapidly. Close examination of these technologies may help plan connectomics projects. Here, we quantitatively compare imaging technologies that have potential to enable whole-brain mammalian connectomics. We perform calculations on electron microscopy (EM) techniques and expansion light-sheet fluorescence microscopy (ExLSFM) methods. We consider techniques that have sufficient resolution to identify all synapses and sufficient speed to be relevant for whole mammalian brains. We offer this analysis as a resource for those considering how to organize efforts towards imaging whole-brain mammalian connectomes.