National Geographic News
A mouse embryo (left) and a transparent mouse embryo (right).

A mouse embryo soaked in saline solution (left) compared with an embryo washed in Scale.

Diagram courtesy RIKEN

Brian Handwerk

for National Geographic News

Published September 2, 2011

A new chemical may soon allow scientists to see exactly what's on your mind—because the substance turns brain tissue totally transparent.

Known as Scale, the new chemical makes body tissue so crystal clear that light can penetrate deeply enough for researchers to directly see fluorescent markers embedded in cells and other structures.

This advance could unveil new frontiers in medical imaging, according to its creators. (See pictures: "Glowing Animals—Beasts Shining for Science.")

"Our current experiments are focused on the mouse brain, but applications are neither limited to mice nor to the brain," Atsushi Miyawaki, of Japan's RIKEN Brain Science Institute, said in a press statement.

We envision using Scale on other organs such as the heart, muscles, and kidneys and on tissues from primate and human biopsy samples."

(Related picture: "See-Through Frog Bred in Japan.")

Paul Thompson, a neurologist at the UCLA School of Medicine who's unaffiliated with the research, said pictures of transparent organs and embryonic mice treated with Scale are incredible.

"I've worked in brain imaging for 20 years, and seeing something like this really had a wow factor," he said.

Transparent Brains to Reveal Drug Activity?

The Scale substance is made from relatively simple ingredients: urea—the prominent compound in urine—glycerol, and a detergent called Triton-X.

Soaking brains and even entire mouse embryos in the chemical solution for two weeks rendered them transparent. (Related pictures: "Weird Fish With Transparent Head.")

Previous substances have been developed to help make cells clearer for medical imaging. But unlike its predecessors, Scale doesn't also wash away the signals of fluorescent proteins, which scientists use to mark neurons, blood vessels, and other small structures in the body.

(See "'Brainbows' Illuminate the Mind's Wiring.")

Fluorescence imaging is currently used, for instance, to map the cellular architecture of the brain, something Scale could make more effective than ever, RIKEN researchers say.

Scale could also be used to help researchers refine their imaging targets before they turn to more complicated, expensive techniques, such as CT scans and MRIs, UCLA's Thompson said.

"I think there is the potential to visually see if treatments are really getting to the parts of the brain or the organ you're trying to target," he said.

"If you have a treatment for Alzheimer's, and the goal is to treat plaques building up in the brain, you might see if a drug is really getting rid of them, and that could be a big boost."

No Living "Invisible Man" ... Yet

Lab animals won't be having "invisible man" experiences any time soon—Scale is too toxic to living creatures, though Miyawaki hopes that limitation can eventually be lifted.

"We are currently investigating another, milder candidate reagent, which would allow us to study live tissue in the same way at somewhat lower levels of transparency," he said.

"This would open the door to experiments that have simply never been possible before."

The transparent-tissue research was published online August 30 by the journal Nature Neuroscience.

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