Light-sheet microscopes customised for imaging the brain

A new generation of custom-built microscopes, capable of capturing exquisite images of the brain, has been described in the journal Nature Methods.

The devices, known as mesoSPIMs (mesoscale selective plane-illumination microscopes), are light-sheet microscopes that optically ‘slice’ samples with a sheet of light — unlike traditional microscopy, in which specimens are sliced with a blade. This optical sectioning captures slivers of image without damaging the sample. The imaged slices are then combined to reconstruct a detailed three-dimensional image of a whole organ or specimen.

However, the datasets produced by standard light-sheet microscopes are very large and analysing them is time-consuming. MesoSPIMs get around this problem with innovative optical technologies that allow fast scanning as well as direct visualisation and quantification of the captured data. By creating high-resolution images of large samples faster than existing microscopes, mesoSPIMs are thus beneficial for rapidly screening many samples.

MesoSPIMs are capable of imaging the minute detail of brain tissue down to individual neurons that are five times thinner than a human hair, and can uncover the 3D anatomy of entire small organs. They can be used to provide new insights into brain and spinal cord organisation for researchers working to restore movement after paralysis or to investigate neuronal networks involved in cognition, pleasure or drug addiction.

This large-scale dataset reveals the developing nervous system of a seven-day old chicken embryo captured with a mesoSPIM microscope. Image credit: mesoSPIM.org.

A new open-source initiative, comprising top European researchers in neuroscience, is now driving dissemination of mesoSPIMs globally by sharing their expertise and excitement as well as images and videos. The mesoSPIM Initiative, started by Dr Fabian Voigt at the University of Zurich, enables the integration of cutting-edge technologies into research labs worldwide, allowing microscope development and brain research to flourish.

“We created the open-source mesoSPIM Initiative to share the latest developments in microscope instrumentation and software with the imaging community,” said Dr Voigt. “Anyone seeking high-quality anatomical data from large samples now has the information they need to build and operate their own mesoSPIM.”

Whole mouse brain stained for vasculature. The image reveals blood vessels, including fine capillaries. Image credit: mesoSPIM.org.

The initiative is aimed at research groups and imaging facilities with experience in building and supporting custom microscopes. A mesoSPIM can be installed in a few days and typically requires a budget of around $200K. There are currently seven mesoSPIMs in operation across Europe and several more instruments under construction.

For more information about the mesoSPIM Initiative, visit http://mesospim.org.

Top image: A mesoSPIM microscope, one of only seven in the world, in the Wyss Center’s microscopy facility in Switzerland. The sample is illuminated with blue light. Image credit: Stéphane Pagès.

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