It is normally an ability associated with superhuman comic book heroes, but scientists have discovered a way of peering through the skin, muscles and bones of animals. The technique turns the layers of tissue transparent, allowing researchers to peer into the body so they can see more delicate features like nerves and veins while they are still inside an animal’s body. They have demonstrated the technique to provide high resolution 3D images of the brain and nervous system of an entire mouse. Their technique could help in the study of diseases like Motor Neuron Disease, Alzheimer’s’ Disease and Parkinson’s Disease. The scientists say they have already been able to use the technique to render large rodents like rats transparent and believe it could even be applied to larger mammals like monkeys. Ultimately they hope to use it on human tissue to help map the human brain. Dr Ali Ertürk, a researcher at the Institute for Stroke and Dementia Research at Ludwig Maximilians University of Munich, said, “We developed a major technology that allows making entire organs and organisms transparent. The new method provides the basis to map neuronal, glial, and vascular connections in the entire lab animals and potentially in deceased human brains.” The researchers used a technique known as tissue clearing to first remove the water by dehydrating it and the oily lipids that form cell membranes using a solvent. Water and lipids can scatter light and are the main parts of mammalian tissues that make them opaque. While tissue clearing has been used for decades to see through tissues, the new approach used by Dr Ertürk and his colleagues also makes it possible to make bones transparent too. It builds on a technique known as 3D Imaging of Sovent-Cleared Organs, or 3DISCO. The team, whose work is published in Nature Methods, have called their approach Ultimate DISCO (uDISCO). It also allows them to express fluorescent proteins in certain tissues, like nerves, allowing them to image them in intricate detail. Dr Ertürk compared it to being able to turn the concrete walls of a building into glass so they can see the pipes and cables that lie beneath. He said, “Now we can see every pipe connection and easily identify if one is disconnected – like disconnected neurons in demented brains. uDisco achieves transparency not only of a single wall but throughout the whole organism.” The process also causes the bodies of the animals to shrink by up to 60 percent but fixes the proteins in the cells in place. By filling the cells of an animal with a fluorescent protein they can then image intricate tissue structures. Dr Ertürk said his team are now already working with other groups around the world to use the technique to study diabetes, stroke, inflammation and Alzheimer’s Disease. He said it would also help in stem cell trails by allowing researchers to see if the cells had integrated into an animal’s tissue or migrated to other parts of the body where they could cause tumours. He said, “I believe the applications are unlimited. Another precious application of method will be to map the human brain. So far there is not any approach, which even comes close to mapping any part of human brain at individual neuron level. Now for the first time we have a powerful tool that can make the human brain transparent and reduce it size to fit an imaging microscope for mapping. However, how the post-mortem human brain neurons will be labelled with fluorescent signal remains a major challenge to be solved beforehand.”