Modern light microscopic techniques provide extremely detailed insights into organs, but the terabytes of data they produce are usually nearly impossible to process. New software, developed by a team led by MDC scientist Dr. Stephan Preibisch and presented in Nature Methods (“BigStitcher: Reconstructing high-resolution image datasets of cleared and expanded samples”), is helping researchers make sense of these reams of data.

It works almost like a magic wand. With the help of a few chemical tricks and ruses, scientists have for a few years now been able to render large structures like mouse brains and human organoids transparent. CLARITY is perhaps the most well-known of the many different sample clearing techniques, with which almost any object of study can be made nearly as transparent as water. This enables researchers to investigate cellular structures in ways they could previously only dream of.

And that’s not all. In 2015 another conjuring trick – called expansion microscopy – was presented in the journal Science. A research team at Massachusetts Institute of Technology (MIT) in Cambridge discovered that it was possible to expand ultrathin slices of mouse brains nearly five times their original volume, thereby allowing samples to be examined in even greater detail.

The software brings orders to the data chaos

“With the aid of modern light-sheet microscopes, which are now found in many labs, large samples processed by these methods can be rapidly imaged,” says Dr. Stephan Preibisch, head of the MDC research group on Microscopy, Image Analysis & Modeling of Developing Organisms. “The problem, however, is that the procedure generates such large quantities of data – several terabytes – that researchers often struggle to sift through and organize the data.”

To create order in the chaos, Preibisch and his team have now developed a software program that after complex reconstructing the data resembles somewhat Google Maps in 3D mode. “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,” explains Preibisch, who has christened the software “BigStitcher.” Now, the computer program, which any interested scientist can use, has been presented in the scientific journal Nature Methods.

A team of twelve researchers from Berlin, Munich, the United Kingdom, and the United States were involved in the development. The paper’s two lead authors are David Hörl, from Ludwig-Maximilians-Universität München and the Berlin Institute for Medical Systems Biology (BIMSB) of the MDC, as well as Dr. Fabio Rojas Rusak from the MDC research group of Professor Mathias Treier. The researchers show in their paper that algorithms can be used to reconstruct and scale the data acquired by light-sheet microscopy in such a way that renders a supercomputer unnecessary. “Our software runs on any standard computer,” says Preibisch. “This allows the data to be easily shared across research teams.“

Image Credit:  Janelia / MDC