Polarized Light Imaging
PLI in a nutshell.
The “Fiber Architecture” research group investigates the structure of nerve fiber connections in the brains of various species—ranging from humans to monkeys, rodents, and birds—at the microscopic level. Our goal is to develop automated measurement and analysis methods that enable high-throughput microscopy and the examination of entire human brains. This requires innovative approaches in the field of high-performance computing to process datasets in the petabyte range.
To this end, we are developing 3D Polarized Light Imaging (3D-PLI) technology, which allows us to visualize and quantify the trajectories of nerve fibers in regions of the cortex, subcortex, and white matter. 3D-PLI utilizes the optical property of birefringence in brain tissue, particularly in the isolating sheath of many nerve fibers, the myelin sheath. Through interaction with the nerve fibers, polarized light is altered in a measurable way. This allows us to determine the direction in which the nerve fibers run and how they bundle into larger fiber tracts. This results in detailed maps of the brain’s fiber architecture. These maps help us understand how the brain is structured, how its connections are organized, and how these structures change in the context of disease.
Since the brain’s connectome must be examined at various spatial scales, we are developing new approaches (e.g., Computational Scattered Light Imaging, comSLI, and Digital Holographic Microscopy, DHM) and integrating complementary imaging methods (e.g., diffusion MRI, chromogenic immunohistochemistry, two-photon microscopy, synchrotron scattering, and electron microscopy) with our collaborative partners.
Our goal is to gain a comprehensive, multiscale understanding of the human brain. In doing so, the brain must not be reduced to a single level of analysis. Of crucial importance is the connectome—that is, the totality of connections between neurons, local circuits, fiber tracts, and brain regions.
We view this organization as a nested system. Synapses and axons initially form local networks on the (sub-)micrometer scale, which then coalesce into larger pathways and ultimately into functional systems. These systems shape perception, behavior, cognition, and disease.
Current imaging already provides key building blocks for this, but remains fragmented. Diffusion MRI and tractography visualize major fiber tracts in living humans, but are indirect and limited in resolution. High-resolution techniques such as polarization, fluorescence, or electron microscopy capture the finest tissue structures, but are usually limited to small or few postmortem samples.
Our vision is to systematically integrate these levels. Macroscopic MRI data should be validated, supplemented, and refined by microscopic tissue data. This will result in multimodal brain atlases that not only schematically map connections but also quantitatively capture their directions, uncertainties, individual differences, and biological variability.
In doing so, we lay the groundwork for a deeper understanding of brain function, behavior, and neurological disorders, and open up new possibilities for diagnostics, research, and personalized medicine.