UNS: Developing Serial Optical Coherence Scanning to Reveal White Matter Changes in SCA1

PI: Akkin, Taner

Proposal Number: 1510674

The objective of this project is to develop an optical imaging technique to study the anatomical changes associated with spinocerebellar ataxia type 1 (SCA1), which is a fatal inherited neurodegenerative disease. Development of the optical technique will enable a comprehensive three-dimensional (3D) reconstruction of the brain and cerebellum, and support quantitative assessments on white matter content and organization. The obtained information may result in the identification of specific markers of the disease and support development of therapeutics in the future.

Serial optical coherence scanning (SOCS) integrates a tissue slicer and a multi-contrast optical coherence tomography for large scale brain imaging at high resolution. It distinguishes white matter and gray matter, and visualizes nerve fiber tracts that are as small as a few tens of micrometers. The retardance contrast due to axonal birefringence highlights the nerve fibers, while the axis orientation contrast indicates their orientation in the plane. In addition, the Purkinje cells and microstructures in gray matter can be visualized by incorporating a microscope objective. The development of SOCS will include a calibration path for obtaining the absolute axis orientation of nerve fibers in the xy plane, and imaging at multiple illumination angles to extract the inclination angle of the fibers with respect to the z-axis. This would represent the fiber orientation in 3D. It will also allow for calculation of the true birefringence. SOCS will be used on three different SCA1 mice models. The investigators hypothesize that as disease progresses towards death of Purkinje cells in nonlethal (ATXN1-82Q) and lethal (SCA1-154Q/2Q) forms, it will manifest in the local and global characteristics of the white matter, which is the axonal and probably the disease carrying pathway to the brainstem and other brain regions. Neither the Purkinje cell death, nor the premature death of the animal occurs for ATXN1-30QD776 mice, which will serve as the control group. Comparative studies will result in better understanding of the SCA1. The project also aims to integrate the research effort with the educational activities that involve general public and students. An exhibit at the Science Museum of Minnesota will be developed for broad dissemination of knowledge to enhance understanding of biomedical optics and the optical imaging technology that allows for high resolution visualizations of the brain. The content will be incorporated in a biomedical optics course taken by both undergraduate and graduate students.