Depolarization-sensitive optical frequency domain imaging (depOFDI) demonstrated strong correlation (r² = 0.862-0.867) with the established NIRS-derived lipid core burden index in 29 patients undergoing coronary intervention. The technique achieved 90% spatial concordance in identifying maximum lipid burden locations within coronary plaques. This represents a significant advance in cardiovascular imaging by potentially consolidating two separate procedures into one comprehensive assessment. Current clinical practice requires both structural imaging via OFDI and compositional analysis via near-infrared spectroscopy to fully characterize coronary plaques prone to rupture. The ability to simultaneously assess plaque structure and lipid content using a single OFDI-based platform could streamline cardiac catheterization procedures while maintaining diagnostic accuracy. However, this preprint study involved only 29 patients from a single intervention setting, limiting generalizability. The technology requires validation across diverse patient populations and plaque types before clinical adoption. As an unreviewed preprint, these promising results await peer scrutiny and replication. If confirmed, this integration could enhance precision in identifying high-risk coronary lesions while reducing procedural complexity and potentially improving patient outcomes in interventional cardiology.