Principle of Stimulated Raman Scattering Microscopy: Emerging at High Spatiotemporal Limits.

Stimulated Raman scattering (SRS) microscopy has revolutionized chemical bond imaging, particularly in biomedicine. However, since its invention in 2008, the theoretical underpinnings of its exceptional sensitivity-surpassing conventional Raman microscopy-have remained largely unexplored. While empirical advancements have driven its success in the following decade, a quantitative understanding of why SRS microscopy performs so effectively has been lacking. This Perspective addresses the knowledge gaps and misconceptions in the field, offering a fundamental theoretical framework for SRS microscopy. Building on recent quantum electrodynamics treatments, we analyze the absolute detection limits of Raman microscopy using a spatiotemporal diagram. Our analysis reveals that spontaneous Raman scattering and stimulated Raman scattering occupy complementary spatiotemporal domains, with the crossover boundary aligning with the length and time scales relevant to bioimaging. Our first-principles theory demonstrates that SRS excels in high spatiotemporal regimes, explaining its unparalleled ability to image chemical bonds, which inherently demand high spatial and temporal resolution. Furthermore, we clarify that SRS spectroscopy and SRS microscopy, though rooted in the same SRS process, operate on distinct principles, serve different purposes, and should not be viewed as natural extensions of one another.