When generating a detailed network model of the brain, nerve fiber crossings pose a major challenge for current neuroimaging techniques. Scientists at Forschungszentrum Jülich have now found that scattered light can be used to resolve the brain's substructure like the crossing angles of the nerve fibers with micrometer resolution. For their studies, the researchers combined microscopy measurements and simulations on supercomputers.
To understand the structure and function of the brain, we need to study the highly complex, three-dimensional pathways of nerve fibers. For a correct reconstruction of the fiber pathways, it is crucial to know the details of fiber architecture at microscopical level, especially in regions with crossing fibers.
One of the most powerful methods to reveal the three-dimensional fiber architecture is 3D Polarized Light Imaging (3D-PLI), a neuroimaging technique developed at Forschungszentrum Jülich. The fiber orientations are reconstructed by shining polarized light through hair-thin brain sections and measuring the resulting intensity changes. 3D-PLI is used, for instance, in the European Human Brain Project to investigate the 3D fiber structures of the brain in unprecedented detail. However, the technique yields only a single fiber orientation for each image pixel, even if the brain tissue is composed of nerve fibers with different orientations. As a consequence, regions with crossing fibers are misinterpreted as fibers pointing out of the section plane.
Now, Miriam Menzel and colleagues at Forschungszentrum Jülich have shown that optical light scattering reveals valuable structural information about brain tissue and can be used to determine crossing nerve fibers and even fiber crossing angles, providing a major enhancement for the reconstruction of complex nerve fiber architectures in the brain. Besides transmission microscopy measurements of various brain sections, the scientists used biophysical modeling and simulations on Jülich supercomputers to explain their experimental observations and develop new imaging methods. The developed simulation framework and results can easily be generalized to other microscopy techniques and fibrous tissue samples, enabling applications beyond neuroscience.
3D-PLI Messung eines Gehirnschnittes (links) zeigt den dreidimensionalen Verlauf der Nervenfaserbahnen in mikroskopischem Detail. In manchen Regionen, z.B. im Bereich von Nervenfaserkreuzungen, werden die Faserorientierungen nicht richtig bestimmt. Simulationen zeigen, dass sich mithilfe von Lichtstreuung (oben rechts) Regionen mit kreuzenden Nervenfasern erkennen und die Kreuzungswinkel der Fasern bestimmen lassen. Dies wurde in experimentellen Studien bestätigt (rechts unten).
Copyright: Forschungszentrum Jülich / Miriam Menzel
Menzel and colleagues found that the intensity of light transmitted through the brain sections depends strongly on the angle at which the light shines on the nerve fibers, but barely on the crossing angles between the fibers themselves. This discovery allows scientists to identify nerve fiber crossings in existing 3D-PLI images and correct misinterpreted nerve fiber orientations in large data sets without repeating any measurements. It also adds valuable 3D information to conventional transmission microscopy images.
In simulation studies, the researchers could show that the distribution of scattered light contains information about the tissue substructure. In further microscopy studies, the researchers demonstrated the great potential of scattering measurements to reveal details of the nerve fiber architecture at microscopical level like the crossing angles of the nerve fibers. The technique allows a more precise reconstruction of nerve fiber crossings in the brain, leading to new insights and a deeper understanding of the structural organization principles of the human brain.
Original publication: Menzel M, Axer M, De Raedt H, Costantini I, Silvestri L, Pavone F S, Amunts K, Michielsen K. Toward a High-Resolution Reconstruction of 3D Nerve Fiber Architectures and Crossings in the Brain Using Light Scattering Measurements and Finite-Difference Time-Domain Simulations.
Physical Review X 10, 021002. Published 2 April 2020. DOI: 10.1103/PhysRevX.10.021002
