What is BrainSaw used for?

Researchers have used BrainSaw serial two-photon tomography to image thousands of brains, generating 3D datasets that can be automatically annotated and registered to a standard atlas for unbiased analyses. The system's major use cases are mapping electrode tracks, brain-wide cell counting, and tracing bulk axonal projections.

Electrode track localisation

Electrodes can be coated with a dye that remains in the tissue after the electrode is withdrawn. Brains are imaged and the dye tracks can be traced and registered to a standard atlas. The brain areas through which each electrode passes can be determined automatically, and penetrations from multiple animals overlaid in a common space. This approach was applied at scale by the International Brain Laboratory (IBL), mapping 699 electrode tracks from 139 mice.

• Typical voxel size: 4 × 4 × 20 µm (~6 GB/channel).
• Throughput: up to six mouse brains per 24 hours.
• Suggested analysis pipeline: brainglobe-segmentation.

Whole-brain cell counting

Techniques such as rabies tracing label individual neurons, revealing connectivity between brain areas. BrainSaw images these samples at high resolution, producing seamless 3D datasets. Automated tools, such as cellfinder, identify the locations of labelled neurons across the brain, allowing researchers to easily quantify cell numbers by brain area. Expressed fluorescent proteins can be localised to the nucleus, if desired, which facilitates automated cell detection.

• Typical voxel size: 2 × 2 × 5 µm (~120 GB/channel).
• Throughput: two to four mouse brains per 24 hours.
• Suggested analysis pipeline: cellfinder.

Bulk projection mapping

Cells can be induced to express fluorescent proteins with viral injections. The protein diffuses throughout each cell, filling somata, dendrites, and axons. Thousands of neurons are labelled by a large injection and the regions to which the population projects can easily be determined by thresholding. The thresholded maps can be registered to a standard atlas for quantitative analysis. In this approach, single axons are not traced, so fine axial sampling is unnecessary.

• Typical voxel size: 4 × 4 × 20 µm (~6 GB/channel).
• Throughput: up to six mouse brains per 24 hours.
• Suggested analysis pipeline: thresholding and brainreg.

Other uses

Single-axon tracing

Reconstructing the morphology of excitatory neurons in mouse barrel cortex, imaged with BrainSaw and registered to the Allen CCF.

Liu et al., Front. Neuroanat., 2022

Atlas template construction

Generating a 3D template volume and brain atlas for the Eurasian blackcap.

Sirmpilatze et al., Current Biology, 2026
(using brainglobe-template-builder)

Mapping widefield data to the Allen CCF

Using cortical blood vessels to project Allen CCF brain area borders onto widefield functional activity in dorsal cortex.

Orsolic et al., Neuron, 2021

Further uses

BrainSaw has also been used for method development, screening AAV expression, mapping lesions, and mapping the locations of implanted optical fibres.