Development of a high-throughput Scattering Polarimeter for studying the connectivity of the nucleus basalis of Meynert in the human brain

• Applicant: Dr. Miriam Menzel
• Subject Area: Experimental and Theoretical Network Neuroscience ; Medical Physics, Biomedical Technology ; Nuclear Medicine, Radiotherapy, Radiobiology ; Optics, Quantum Optics and Physics of Atoms, Molecules and Plasmas
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 498596755

The aim of this project is to realize a Scattering Polarimeter that uniquely combines state-of-the-art light scattering and polarization measurements of brain tissue and enables for the first time to reveal the intricate, crossing nerve fiber pathways in large brain volumes, such as the nucleus basalis of Meynert and its connections to cortical brain areas. Unraveling the highly complex and densely grown network of nerve fibers in the brain is key to understanding its structure and function and to assist brain surgery. The microscopy technique 3D Polarized Light Imaging (3D-PLI) determines the spatial course of nerve fiber pathways in whole histological brain sections with micrometer resolution. However, it does not provide information about the tissue composition and leaves uncertainties in pixels containing crossing fibers. With Diattenuation Imaging (DI), a promising new imaging technique has been developed that has the potential to distinguish different tissue compositions (e.g. regions with different fiber diameters). The recently developed technique Scattered Light Imaging (SLI) finally allows to retrieve the individual orientations of crossing nerve fibers, by illuminating brain sections from many different angles and studying the resulting patterns of scattered light. Combining all three techniques in one system (Scattering Polarimeter) will reveal the individual 3D fiber orientations with micrometer resolution, both in regions with densely packed and crossing nerve fibers. However, with the current measurement procedure, SLI measurements take several hours (requiring thousands of illumination angles) so that measurements of larger anatomical structures or nerve fiber networks are not feasible. One central aim of this project is therefore to reduce the required measurement time, using compressed sensing – a method that employs data compression approaches already during data acquisition. In this way, a high-throughput Scattering Polarimeter will be realized that enables combined measurements of many consecutive brain sections and multi-modal image analysis of larger brain volumes. The new system will be used to create a tissue model of the nucleus basalis of Meynert (NBM), which plays an important role in memory, attention, visual function, and motor control. Studies have shown that low-frequency, deep brain stimulation of the NBM are beneficial for the treatment of neurodegenerative dementias such as Alzheimer’s or Parkinsons’ disease. For successful treatment, precise positioning of electrodes in the brain is required. Hence, a detailed knowledge about the NBM fiber pathways and their connections to cortical brain areas is crucial. The new high-throughput Scattering Polarimeter will be used to measure a large brain volume (containing the NBM and cortical areas) to reveal the intricate nerve fiber pathways and crossings at microscopic detail, providing crucial knowledge for better treatment of neurodegenerative dementias.

• DFG Programme: Research Grants