Want to Look Inside a Brain? With Transparent Organs, You Can

 wired.com  02/21/2020 12:00:00   Matt Simon

Your organs are a lot of thingsa powerful computer (in the case of your brain), detoxers (your liver and kidneys), breathing devices (your lungs). But theres one thing theyre decidedly not: transparent.

Thats unless youre Kevin Bacon in The Invisible Man, or if your organs end up in the lab of Ali Ertrk, director of Helmholtz Munichs Institute for Tissue Engineering and Regenerative Medicine. Writing in the journal Cell, Ertrk and his colleagues detail how theyve treated human organs to make them see-through. Next, by adding special dyes to the now-transparent organs, they can map kidneys, eyes, and brains on a cellular level, which could one day help scientists 3D-print versions of them.

Video: Helmholtz Zentrum Mnchen/Ertrk lab

You dont have to turn a brain transparent to see inside it, of course. An MRI can image the insides of a brain in detail, and a functional MRI (fMRI) measures brain activity by looking at blood flow. But to get at whats happening on a cellular level, normally you would have to section the brain, damaging it as you cut into it. The beauty of this new technique is that the researchers can keep a transparent organ entirely intact while still peering deep inside it, seeing right down to the cellular level. They can image networks of teeny-tiny blood vessels, undisturbed in their natural arrangement. For example, in the kidneys, they can see tufts of fine capillaries known as glomeruli structures, which help filter urine.

You may have already seen Ertrks previous work making mice transparent to study how they respond to injury. (Dead mice, to be clear.) Working with human organs, though, the team ran into a problem: stiffness. The mice they used in the earlier experiment were only a few months old, so their tissues were nice and soft, allowing chemicals to penetrate them. The human organs they had to work with were from much older individuals, and they had accumulated gobs of stiff molecules like collagen over the yearsa perfectly natural fact of life, by the way.

We had to somehow find a way to relax this stiffness, says Ertrk. The solutionin more than one sense of the wordwas a zwitterionic detergent (read: not available in your average drug store) called CHAPS, which could penetrate through these stiff molecules and form small channels that would then allow the passage of the solution.

Video: Helmholtz Zentrum Mnchen/Ertrk lab

The team could then dehydrate the organ with alcohol and remove the lipids, or fats, by using the solvent dichloromethane (which is also used to decaffeinate coffee). Because this process entails removing so much material, each organ was also pretreated with paraformaldehyde so it wouldnt decompose, collapsing in on itself during the process. So everything is fixed in time and space, says Ertrk.

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