Biorthogonal metabolic imaging of brain during aging and diseases (Invited Paper)

Understanding brain lipid metabolism is vital for unraveling brain aging and neurodegeneration mechanisms. Traditional imaging methods lack chemical specificity and resolution. Stimulated Raman scattering (SRS) imaging provides high specificity, resolution, and deep penetration. We utilize a multimodal imaging platform integrating deuterium isotope probed SRS microscopy (DO-SRS), multiphoton fluorescence (MPF), and second harmonic generation (SHG) to visualize lipid dynamics in animal brains. Deuterium incorporation generates detectable carbon-deuterium bonds in lipids, revealing turnover. We find decreased lipid activity during aging and neurodegeneration in Drosophila brains, with interventions like dietary restriction and pathway modulation enhancing turnover. Our advanced imaging and analysis methods offer high-resolution insights applicable to diverse biomedical studies.