Advancing Brain Imaging: Illuminating Neural Pathways with a New Technique

Caption: Color-coded nerve fiber orientations in a brain section obtained from Scattered Light Imaging (SLI) and Small-Angle X-ray Scattering (SAXS). Credit: TU Delft

Researchers have developed a novel brain imaging technique called Scattered Light Imaging (SLI) that offers a cost-effective and high-resolution method for mapping neural connections in the brain. By analyzing light scattering patterns in thin brain slices, SLI provides more detailed results compared to existing methods like diffusion magnetic resonance imaging (dMRI). Moreover, SLI is more accessible and faster than Small-Angle X-ray Scattering (SAXS), making it a promising alternative for studying complex neural networks.

Untangling the intricate web of nerve fibers within the brain has become more attainable with the advent of scattered light imaging (SLI). Collaborative efforts by researchers from Delft, Jülich (Germany), and Stanford (USA) have successfully combined light and X-ray scattering with MRI to discern nerve fiber trajectories, even in regions with densely intertwined fibers. SLI has proven to be exceptionally effective in revealing these trajectories with the highest level of detail, while also offering significant advantages in terms of speed and affordability over X-ray and MRI techniques. This precise mapping is crucial for advancing our understanding of how nerve fibers are interconnected within the brain.

Crucial Pathways in the Brain

The brain’s various regions are interconnected through billions of nerve fibers, which play a vital role in maintaining proper brain function. Constructing a comprehensive map of all neural connections heavily relies on imaging techniques capable of disentangling these fibers, most of which are only micrometers thin. Particularly challenging are regions where nerve fibers are densely packed and intricately interwoven. Dr. Miriam Menzel, Assistant Professor at the Department of Imaging Physics of TU Delft, developed the SLI technique specifically to study these intricate fiber arrangements. She explains, “By illuminating hair-thin brain slices with light from different angles and analyzing the resulting scattering patterns, we are not capturing images of neurons or synapses; rather, we are seeking to understand their wiring. This knowledge is essential for comprehending brain function and dysfunction.”

Accessible, Affordable, and Swift

Small-Angle X-ray Scattering (SAXS) is a well-established method used in material science to examine the organization of different structures using a synchrotron. On the other hand, diffusion magnetic resonance imaging (dMRI) is a crucial technique employed in clinical settings to visualize the brain’s three-dimensional nerve fiber network. Dr. Menzel and her team have demonstrated that SLI data obtained from brain slices align with the results obtained from SAXS and dMRI. However, SLI surpasses dMRI in terms of resolution while also offering greater accessibility, affordability, and speed compared to both techniques. This milestone achievement paves the way for SLI to be implemented using a simple LED light source and camera, requiring just a few seconds for measurements. Its portability allows for easy setup in pathology laboratories, facilitating clinical research endeavors.

Microscopic Precision

Dr. Menzel has dedicated several years to refining the SLI technique, initially in Jülich and now in Delft. In collaboration with her colleagues at Stanford, she successfully conducted SAXS and dMRI measurements on brain samples previously imaged using SLI. “Most imaging techniques struggle to differentiate individual pathways within densely structured areas of the brain that contain numerous entangled or interwoven nerve fibers,” explains Dr. Menzel. “SLI excels in providing highly precise fiber orientation maps within these dense regions.” Particularly, SLI demonstrates exceptional accuracy in discerning the two-dimensional (“in-plane”) fiber orientations.

Future Directions

“As a member of the Delft research community, I am thrilled about the opportunities for further developing this technique and exploring new applications,” says Dr. Menzel. The team intends to extend the use of SLI to study other types of fibers, such as muscle and collagen fibers, and expand the tissue area that can be investigated. The ultimate goal is to create a compact and portable SLI system that can be readily deployed in other laboratories. Furthermore, the team envisions the long-term application of this technique in clinical settings.

Reference: “Using light and X-ray scattering to untangle complex neuronal orientations and validate diffusion MRI” by Miriam Menzel, David Gräßel, Ivan Rajkovic, Michael M Zeineh, and Marios Georgiadis, 11 May 2023, eLife.
DOI: 10.7554/eLife.84024

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• “Using light and X-ray scattering to untangle complex neuronal orientations and validate diffusion MRI” by Miriam Menzel, David Gräßel, Ivan Rajkovic, Michael M Zeineh, and Marios Georgiadis. Link