Optimization of surface enhanced spatially offset Raman spectroscopy for applications in pre-clinical cancer imaging

Achieving high selectivity and specificity in deep tumor imaging remains a critical challenge in optical imaging. While Raman spectroscopy has been widely used for imaging various tissues, its penetration depth in vivo is limited. Here, we introduce a novel approach that integrates Spatially Offset Raman Spectroscopy (SORS) with Surface Enhanced Raman Scattering (SERS) nanoparticles, known as Surface Enhanced Spatially Offset Raman Spectroscopy (SESORS), for in vivo imaging of deep-seated tumors. We detail the optimization of SORS instrumentation to improve signal-to-noise ratio (SNR), spectral resolution, and depth acquisition as well as methods to reduce overall acquisition times. Our results demonstrate that through optimization of instrumentation, SESORS enhances the non-invasive detection of tumors across various models, and can effectively complement existing radiologic techniques.