Graduation Year


Document Type

Master's Thesis


Master of Science


Biological Science

Program Director

Meredith Protas, PhD

First Reader

Danielle Tan

Second Reader

Manuel Lopez


This study focused on developing a set of advanced histological tools to conduct spatial analysis of the central nervous system (CNS), improving upon traditional methods, and addressing their shortcomings. We applied these methods to explore CNS drug biodistribution. With the goal of defining regions of tissue in which the drug is distributed and the specific cell types that uptake it, we employed tissue clearing, immunofluorescent staining of unique cellular population-identifying antigens, and light-sheet fluorescence microscopy (LSFM) techniques to image adult mouse hemispheres in a variety of conditions and compared these techniques to traditional immunofluorescence (IF) on thin tissue sections. In addition, we used high-content spatial proteomics to observe the regional and cellular subtype localization and concentration-dependent changes to a reporter-tagged adeno-associated virus (AAV) following intracerebroventricular (ICV) delivery. Here we have improved upon standard technical counterparts and used advanced histological techniques, 3D clearing combined with LSFM and high-content spatial proteomics, to shed light on regional and cell-specific drug biodistribution within the brain.

Available for download on Sunday, March 28, 2027