Sven Hildebrand can’t quite explain why, but images of the human brain have a strong aesthetic appeal to him. He can spend hours staring at cross sections of the brain. He recently gifted his brother a framed microscope photograph of a brain region, which is now displayed on his brother’s living room wall. “I might follow his example. I have some brain pictures on my desk, but not above the TV yet.”
Hildebrand (33) was born in Zeitz near Leipzig, Germany. Last week, he received the 2023 Dissertation Prize for his PhD research on a novel imaging technique known as optical tissue clearing. This technique allows scientists to render tissues and organs transparent using a chemical approach, enabling them to be viewed in 3D through a specialised microscope.
More complete image
While it all sounds – and is – very high-tech, the concept was invented more than a century ago. Around 1900, the German anatomist Werner Spalteholz already conducted experiments with rendering veins in the human hand transparent. “His approach was simple but aggressive, resulting in significant tissue damage”, says Hildebrand. “In 2007, the University of Vienna breathed new life into tissue clearing by using a specialised light-sheet microscope. In 2013, the technique made the cover of the scientific journal Nature, sparking international interest.”
Scientists traditionally visualise organs and other tissues by cutting them into very thin 2D slices, which are then used to create a 3D reconstruction. A German research team managed to map the entire brain this way in 2013, but it took years. “With this new technique, it should theoretically take a matter of months. And rather than an entire research institute, it should take just a handful of researchers.”
The technique can also provide a more comprehensive view of the tissue. “If you can only examine a few slices, you run the risk of overlooking something.”
Neocortex
Hildebrand used optical tissue clearing to map the brain more accurately than ever before. “Cells and blood vessels are organised differently in each brain region. This technique shows the boundaries between some of those regions very clearly. It allows you to create a more reliable map of the brain. And knowing where you are is as important to a neuroscientist as it is to a hiker.”
Much of Hildebrand’s research focuses on the structure of the neocortex. “Simply put, the neocortex is the brain region just below the skull. We use it for thinking, but also for self-control, planning, and so on. There’s still a lot we don’t know about the structure of the neocortex.”
A matter of counting
Hildebrand hopes that the novel technique will also bring us closer to answering some fundamental questions, such as how many cells are in the human brain. “People throw around numbers like 80 or 100 billion, but these are estimates based on traditional 2D data. Optical tissue clearing allows you to visualise the entire brain and determine the exact number. It’s a matter of counting.”