Anna Novoseltseva: BME PhD Defense

Title: "Volumetric assessment of cerebral myelin integrity with polarized light-based methods"

Advisory Committee: Dr. Irving Bigio (Advisor) Dr. David Boas (Advisor) Dr. Darren Roblyer (Chair) Dr. Lei Tian Dr. Douglas L. Rosene Dr. Hui Wang

Abstract: This dissertation reports development of comprehensive methods for assessing myelin integrity in neurodegenerative diseases using label-free optical imaging. The work consists of four interconnected studies addressing technical challenges and methodological limitations in myelin research. An initial investigation of myelin degradation in Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE) using polarization-sensitive optical coherence tomography (PS-OCT) and birefringence microscopy (BRM) identified myelin structural changes but also revealed critical confounding factors, particularly postmortem interval (PMI) effects, and highlighted the impractical time requirements for manual image analysis. To address the analysis bottleneck, an automated deep-learning (DL) system for myelin defects detection was developed, achieving statistically strong accuracy while reducing analysis time 14-fold. A comprehensive methodology chapter provides standardized protocols for the research community, including advanced imaging techniques and systematic validation approaches. Finally, a controlled PMI study using a rhesus macaque model systematically characterizes confounding factors discovered in the initial work. This integrated approach provides validated tools, standardized protocols, and systematic understanding of limitations necessary for reproducible myelin assessement in neurodegeneration.