Hybrid Raman and Partial Wave Spectroscopy Microscope for the Characterization of Molecular and Structural Alterations in Tissue.

We present a hybrid Raman spectroscopy (RS) and partial wave spectroscopy (PWS) microscope for the characterization of molecular and structural tissue alterations. The PWS performance was assessed with surface roughness standards, while the Raman performance with a silicon crystal standard. We also validated the system on stomach and intestinal mouse tissues, two closely-related tissue types, and demonstrate that the addition of PWS information improves RS data classification for these tissue types from R² = 0.892 to R² = 0.964 (norm of residuals 0.863 and 0.497, respectively). Then, in a proof-of-concept experiment, we show that the hybrid system can detect changes in intestinal tissues harvested from a tumorigenic Villin-Cre, Apc^fl/wt mouse. We discuss how the hybrid modality offers new abilities to identify the relative roles of PWS morphological features and Raman molecular fingerprints, possibly allowing for their combination to enhance the study of carcinogenesis and early cancer diagnostics in the future.