Mouse organs made transparent with dye for visualization

Massaging common food coloring into the skin of a live mouse makes the animal’s tissue transparent, allowing researchers to see its blood vessels and organs working — a technique that may one day help doctors peer deeper into our bodies to diagnose diseases.

It’s not easy to see the internal environment of a live animal. If the animal is dead, we can get a better look by sectioning the tissue or using chemicals to remove proteins and fats. In live animals, some things can be seen with a scan or endoscopy, but to see live tissue, you often have to cut it up.

Now, Zhihao Ou and his colleagues at the University of Texas at Dallas have succeeded in making mouse tissue transparent by rubbing the skin of live mice with the food dye tartrazine, also known as E102 or Yellow 5. When the skin absorbs the dye molecules, it changes the tissue’s refractive index — the speed at which light passes through the skin.

The mice then became transparent, enabling the researchers to watch peristalsis, the muscular contractions that move food through the digestive tract, and to view blood vessels on the surface of the mouse brain.

To understand how this technology works, Oh says, think of carbonated water. Light passing through the liquid changes direction each time it goes from the water to the air bubbles and back again, Oh says. That means the light scatters in all directions and doesn’t penetrate the liquid as easily as it does flat air or water. Biological tissue behaves in a similar way because it contains not only a lot of water, but also other molecules like lipids and proteins, which typically have a higher refractive index than water.

Adding the dye brings the refractive index of water closer to that of lipids and other molecules in the tissue, scattering light less, “which means you can see deeper and probe deeper,” Ou says.

The dye can be washed off and does not appear to harm the rats.

The research gets to the heart of one of the biggest problems in microscopy, says Christopher Rowlands of Imperial College London. “If you tried to see more than a millimetre from the surface of a tissue, you couldn’t. You just couldn’t do that before. Now suddenly you can,” he says. “Previously you could only see millimetres, now you can see centimetres away, and those centimetres make a huge difference in many applications.”

Rowlands says that tartrazine could potentially be toxic if applied to the skin in large amounts, but neurobiologists routinely stick probes and lenses into the brain and remove parts of the cortex, so using a dye that’s widely accepted as safe for ingestion on the skin would probably be less harmful, he says.

But while the technique makes skin more transparent, it won’t give doctors complete visibility inside a person’s body. “It’s not like Harry Potter’s invisibility cloak,” Rowlands says. “It will make the skin look more like glass than it should.” Even if the effect worked throughout the body, Rowlands says, doctors would still be able to see bones and specialized structures inside cells called organelles.