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New Technique Lets Scientists See Through Whole Organisms

by Michael Keller

Seeing is believing when it comes to understanding how organisms work. For biologists trying to learn about what’s going on inside a body, one of the biggest obstacles is not being able to put their eyeballs on a part or system without other objects getting in the way. The answer is usually going in with one invasive tool or another, which ends up damaging or destroying the thing they’re trying to investigate. 

Now California Institute of Technology scientists say they have improved upon a solution to clearing up the picture. The technique builds on work that garnered widespread attention last year. In that effort, assistant professor of biology Viviana Gradinaru and her team used detergent and a polymer to make a rodent brain transparent for study in unprecedented detail. 

"Large volumes of tissue are not optically transparent—you can’t see through them," Gradinaru says in a statement. “We have to slice the tissue very thin, separately image each slice with a microscope, and put all of the images back together with a computer. It’s a very time-consuming process and it is error prone.”

By improving on the process, they can now dissolve the light-blocking lipids in cells for a whole organ or an entire organism using its own blood vessels to deliver the . They then infuse a hydrogel that maintains the structure of the cells and lets investigators see in three dimensions through multiple layers of tissue.

"The payoffs of such a method are optical access throughout large volumes of tissues, enabling the study of cell-to-cell spatial relationships and long-range neural connectivity in the context of preserved tissue morphology," the researchers write in the article on their work published recently in the journal Cell.

They call their approach PARS (perfusion-assisted agent release in situ) using a cocktail of hydrogel, clearing and imaging chemicals called RIMS (refractive index matching solution), and they say it lets a researcher see intact tissues and systems using standard microscopy methods.

While this imaging technique will help biologists see the larger picture in how organisms are put together, Gradinaru says they have already used it to investigate a human tumor. She says it could one day be used as a diagnostic tool to rapidly detect cancer cells.

"I think these new techniques are very practical for many fields in biology," she says. "When you can just look through an organism for the exact cells or fine axons you want to see—without slicing and realigning individual sections—it frees up the time of the researcher. That means there is more time to the answer big questions, rather than spending time on menial jobs."

All images courtesy Bin Yang and Viviana Gradinaru/Caltech/Cell. Gif created from movie supporting authors’ research. Courtesy V. Gradinaru et al./Cell.

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