Characterizing microstructural changes that occur in neurodegenerative diseases is vital for understanding pathogenesis and developing effective treatments. Diffusion tensor imaging (DTI) is an extremely useful technique to illustrate microstructural anatomy in the brain in vivo. A drawback to this imaging technique is a relatively low isotropic resolution (2mm.) At this resolution, axonal pathways – especially crossing pathways – become distorted. With the use of histological sections, there are higher-resolution alternatives to DTI. One of these is the use of polarized light imaging (PLI).
PLI utilizes the physical properties of myelin to infer axon direction. The myelin sheaths surrounding axons contain lipids and proteins. The radial arrangement of these biomolecules leads to predictable birefringence of linearly-polarized light. By measuring the degree of birefringence, the 3-D orientation of axons can be calculated based off of the refractive properties of the surrounding myelin. Utilizing image-processing algorithms, the tissue section can be viewed with the DTI color-scheme at a resolution on the micron scale. In collaboration with Prof. Dr. med. Hubertus Axer at Jena University Hospital, Germany, we are developing protocols and equipment to capture PLI images of whole-brain histological sections with an aim to characterize disease-related changes to neuronal connectivity and brain microanatomy.