Optical biomarker of metabolism for breast tumor diagnosis: Insights from subcellular dynamics

Label-free metabolic dynamics contrast is highly appealing but difficult to achieve in biomedical imaging. Interference offers a highly sensitive mechanism for capturing the metabolic dynamics of the subcellular scatterers. However, traditional interference detection methods fail to isolate pure metabolic dynamics, as the dynamic signals are coupled with scatterer reflectivity and other uncontrollable imaging factors. Here, we demonstrate active phase modulation-assisted dynamic full-field optical coherence tomography (APMD-FFOCT) that decouples and quantifies the metabolic dynamics by adding a reference movement for all interferential scatterers. This novel technique enables imaging and dynamic analysis of subcellular structures along with their changes during the apoptotic process in tumor tissues. Furthermore, the nucleus-to-cytoplasm dynamic intensity ratio could serve as an optical biomarker for breast tumor grading, enhancing intraoperative diagnosis.