Scattered Light Imaging Reveals Pathways of Nerve Fibers in the Brain

The different brain areas are connected by billions of nerve fibers

Disentangling complex nerve fibers in the brain has recently become easily accessible with scattered light imaging (SLI): researchers in Delft, Jülich (Germany) and Stanford (USA) have successfully combined light and X-ray scattering with MRI to reveal the pathways of nerve fibers distinguishable from each other, also in brain regions with highly cross-linked fibers. SLI exposed the orbits down to the smallest detail, while the technique is significantly faster and cheaper than X-ray scattering and MRI. To better understand how nerve fibers are wired in the brain, it is essential to map the entanglements in detail. The research has been published in the journal eLife.

Connections in the brain
The different brain areas are connected by billions of nerve fibers. These connections are essential for the proper functioning of the brain. The search for a comprehensive map of all neural connections stands or falls with imaging techniques that can untangle these fibers, often no more than about a micrometer thin. Particularly challenging are areas of densely packed and highly intertwined nerve fibers. Miriam Menzel, assistant professor at the Department of Imaging Physics at TU Delft, developed the SLI technique to study such fiber constellations: “We shine light from different angles through hair-thin brain slices and analyze the patterns created by the scattered light. We don’t take a picture of neurons or synapses; we want to know how they are wired. That’s important to understand how the brain functions and what can go wrong.”

More accessible, cheaper and faster
Small-angle X-ray scattering (SAXS) is an existing method in materials science to investigate how different structures are organized with a synchrotron, while diffusion magnetic resonance imaging (dMRI) is an important clinical technique for mapping the three-dimensional nerve fiber network of the brain. “We have now shown that the results of SLI are consistent with those of SAXS and dMRI in the brain slices studied, but SLI offers higher resolution than dMRI and is more accessible, cheaper and faster than the other techniques. This is an important milestone.” Menzel says. “We can perform SLI measurements with a simple LED lamp and camera within seconds, without the need for synchrotrons worth millions of euros or MRI scanners. And as a portable system, SLI could easily be deployed in pathology laboratories to support clinical research.”

Microscopic resolution
Menzel has been working on the SLI technique in recent years, first in Jülich and now in Delft. She also implemented it at Stanford, where her fellow researchers performed SAXS and dMRI measurements on brain samples that had also been examined with SLI. “Most imaging techniques have difficulty distinguishing individual pathways in dense brain structures that contain many intertwined or entwined nerve fibers,” Menzel explains. “SLI provided fiber orientation maps with microscopic resolution for these packed regions.” Especially the two-dimensional (horizontal) fiber orientations were distinguished with great accuracy.

Next steps
“Being in Delft offers great opportunities to further develop SLI and to work on new applications,” says Menzel. The team plans to also apply SLI to other types of fibers, such as muscle and collagen fibers, and to increase the area of ​​tissue that can be studied. The aim is to develop a small and portable system that can easily be used in other labs. “In the long term, we hope to apply the technique in clinics as well.”

Bron: Tu Delft

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