Zoom in, plot your course: A virtual GPS map for tissues

This virtual cross section of the complete nervous system of a fruit fly larva is stitched together from different slides at nanometer resolution represented by different colored sections. (Janelia/Max Delbrück Center)

Using terabytes of data derived from different microscopy techniques, researchers have developed a program that reconstructs tissue slides into a navigable, three-dimensional organ model that can illustrate cellular functions such as gene expression. 

Researchers combined individual images from both light-sheet and expansion microscopy to assemble virtual 3D models with nanometer resolutions. This allows, in one example, the complete visualization of a fruit fly larva’s nervous system, while tracking individual nerve cells to provide a new look at the function of neurons.

It can also characterize differences in the brain tissue between genetically modified mice at the single-cell level, to help understand any potential differences in behavior, the researchers said.

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The developers of the open software, presented in the journal Nature Methods, describe it as a “Google Maps for tissues” and say it can run on just about any computer.

“One can not only get an overview of the big picture, but can also zoom in to specifically examine individual structures at the desired resolution,” said Stephan Preibisch, head of a research group on microscopy, image analysis and modeling of developing organisms at the Max Delbrück Center for Molecular Medicine in Berlin.

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The software, dubbed BigStitcher, was developed by 12 researchers from Berlin, Munich, the U.K. and the U.S. over about a decade. The program can also automatically assess individual image quality and lets researchers rotate the model to view all aspects of the organ.

And by zooming in, users can see where cell division is taking place within a brain or highlight areas of high RNA expression. “In order to find all this out, it is first necessary to get an overview of the entire object of study, but then to be able to zoom in to view the smallest of details in high resolution,” Preibisch said.

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