Development of advanced Raman microscopy methods to interrogate the brain
Thesis Defense in Chemistry
Presented by Mian Wei, Min Group
A central quest in biology is to understand the structure-function relationship of complex biological systems. Compared to other organ systems, the brain represents the ultimate complexity. Accordingly, many grand challenges endure in brain science, including comprehensively mapping neuronal wiring of the brain, an exhaustive taxonomy of cell types in the brain, and robust diagnostic and therapeutic strategies for brain diseases. These challenges are difficult to tackle with existing techniques and call for advances on novel microscopy methods. The evolution of modern Raman microscopy is fundamentally driven by novel spectroscopy methods. Notable innovations include stimulated Raman scattering (SRS) microscopy and electronic pre-resonance SRS (epr-SRS) microscopy. Despite these advances, the imaging depth of Raman microscopy is limited to superficial layers of biological tissues (~100 μm) due to light scattering. This dissertation contributes to the development of advanced Raman microscopy methods for volumetric imaging with extended imaging depth in scattering tissues. For this purpose, we develop a set of tissue clearing strategies tailored to specific Raman imaging modalities. In addition, we develop image analysis methods to extract systems information from volumetric high-dimensional imaging datasets. Equipped with our toolbox of volumetric imaging and analyses, we elucidate intricate structures and functions of the brain at both physiological and pathological conditions, providing implications for brain tumor metabolism and cerebellum development.