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Updated: May 10, 2026

Array Tomography Workflow for the Targeted Acquisition of Volume Information using Scanning Electron Microscopy

Array Tomography Workflow for the Targeted Acquisition of Volume Information using Scanning Electron Microscopy

Published on: July 15, 2021

Studying synapses in human brain with array tomography and electron microscopy.

Kevin R Kay¹, Colin Smith, Ann K Wright

¹Massachusetts General Hospital and Harvard Medical School, MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA, USA.

Nature Protocols

|June 22, 2013

Summary

This summary is machine-generated.

Array tomography (AT) enables high-throughput synapse analysis in human brain tissue, overcoming limitations of traditional microscopy. This method allows detailed synapse phenotyping for neurodegenerative and psychiatric disease research.

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Area of Science:

Neuroscience
Biotechnology
Pathology

Background:

Postmortem human brain synapse studies face limitations due to light microscopy resolution and electron microscopy (EM) ultrastructure preservation challenges.
Existing methods hinder comprehensive analysis of synapse density and protein composition in clinical cohorts.

Purpose of the Study:

To introduce and validate Array Tomography (AT) as a method for high-throughput synapse analysis in postmortem human brain tissue.
To enable detailed synapse phenotyping for clinicopathological correlations in neurodegenerative, developmental, and psychiatric diseases.

Main Methods:

Array tomography (AT) protocol involving embedding autopsy tissue in resin and sectioning into ultrathin serial ribbons.
Immunofluorescence imaging of serial sections for high-throughput synapse density and protein composition assessment.
Complementary transmission electron microscopy (TEM) for ultrastructural analysis of preserved human brain samples.

Main Results:

AT allows imaging of tens of thousands of synapses per case, overcoming previous resolution and preservation limitations.
The protocol is efficient, taking approximately 3 days per case (excluding image analysis).
Combined AT and TEM provide both high-throughput and ultrastructural data for synapse phenotyping.

Conclusions:

Array tomography offers a powerful approach for detailed synapse phenotyping in postmortem human brain tissue.
Integrating AT and TEM into brain banking facilitates the study of clinicopathological correlations at the synapse level.
This methodology is crucial for advancing research in neurodegenerative, developmental, and psychiatric disorders.