Scientists Achieve Unprecedented 3D Brain Mapping with X-Ray Technology
A groundbreaking advancement in neuroimaging has enabled scientists to map brain tissue in three dimensions with unprecedented resolution using X-rays, offering a non-destructive method to overcome long-standing technological limitations. The research, a collaboration between the Paul Scherrer Institute (PSI) in Switzerland and the Francis Crick Institute in the UK, promises to unlock new understandings of the brain’s complex architecture and could accelerate research into neurological diseases.
The ability to visualize the intricate wiring of the brain has long been hampered by the challenges of traditional imaging techniques. Existing methods, such as volume electron microscopy, require slicing brain tissue into incredibly thin sections – tens of thousands of them for even a small sample – and then painstakingly reconstructing a 3D map.This process is not only time-consuming and prone to errors but also results in inevitable data loss.
“The brain is one of the most complex biological systems in the world,” explains Adrian Wanner, Group Leader of the Structural Neurobiology Research Group at PSI. His team is focused on connectomics, the field dedicated to unraveling how neurons are wired together. “If you look at a cell body in the brain and the liver, it’s not easy to distinguish the two,” Wanner noted. “What is really different is how the brain cells are organised and connected.”
Consider the sheer scale of this challenge: within just one cubic millimeter of brain tissue, ther are approximately 100,000 neurons connected by roughly 700 million synapses and 4 kilometers of neural “cabling.” Understanding these connections is crucial, as they dictate brain function and are implicated in conditions like Alzheimer’s disease. As Wanner succinctly put it, “It’s a huge amount of details.”
To overcome these limitations, the researchers developed a novel X-ray imaging technique called coherent scattering X-ray microscopy (cSAXS). complementing this, they developed a specialized stage that cools samples to -178 degrees Celsius using liquid nitrogen, and a reconstruction algorithm to correct for any remaining deformation.
Using this method, the researchers successfully imaged mouse brain tissue up to 10 microns thick, achieving a resolution of 38 nanometers in three dimensions. “We believe this marks a record resolution using X-ray imaging on an extended biological tissue,” Diaz stated. At this resolution,they were able to reliably identify synapses,axons,and dendrites – key features of neuronal connections.
“This is not breakthrough information on the brain: it matches the best results with state-of-the-art volume electron microscopy – the current gold standard,” Wanner clarified. “What’s exciting is that this marks the start of what’s to come.”
The Future is Brighter with the SLS Upgrade
While a 10-micron sample may seem small, it represents a meaningful leap forward compared to the minuscule slivers used in electron microscopy. Currently, the primary limitation is acquisition time – reconstructing a high-resolution image can take days. This bottleneck is directly related to the intensity of the X-rays.
The researchers are employing a technique called ptychography, which utilizes coherent X-rays and doesn’t require lenses. “Coherence is exactly where we are set to gain with the SLS upgrade,” Diaz explained.
The SLS has recently undergone a complete upgrade to become a 4th-generation synchrotron, the most advanced type of synchrotron in the world. This upgrade will increase the flux of coherent X-rays at the cSAXS beamline by up to one hundred times.
“With one hundred times more X-ray photons hitting our sample every second, we will be able to – in principle – either image the sample one hundred times faster or image volumes one hundred times larger,” Diaz said. “In practice, we will need to learn how to do this in an efficient way. But the potential is there.”
The publication of this research coincides with a significant milestone: the first X-rays were observed at cSAXS following the upgrade in july 2025. with the major technical hurdles overcome, the path is now clear for studying much larger samples of brain tissue in 3D at high resolution, promising a new era in our understanding of the brain.
