High-Resolution Imaging of Morphological Changes Associated with Apoptosis and Necrosis Using Single-Cell Full-Field Optical Coherence Tomography.

Full-field optical coherence tomography (FF-OCT) is a high-resolution interferometric imaging technique that enables label-free visualization of cellular structural changes. In this study, we employed a custom-built time-domain FF-OCT system to monitor morphological alterations in HeLa cells undergoing doxorubicin-induced apoptosis and ethanol-induced necrosis at the single-cell level. Apoptotic cells showed characteristic features such as echinoid spine formation, cell contraction, membrane blebbing, and filopodia reorganization. In contrast, necrotic cells exhibited rapid membrane rupture, intracellular content leakage, and abrupt loss of adhesion structure. These dynamic events were visualized using high-resolution tomography and three-dimensional surface topography mapping. Furthermore, FF-OCT-based interference reflection microscopy (IRM)-like imaging effectively highlighted changes in cell-substrate adhesion and cell boundary integrity during the cell death process. Our findings suggest that FF-OCT is a powerful imaging platform for distinguishing cell death pathways and assessing dynamic cellular states, with potential applications in drug toxicity testing, anticancer therapy evaluation, and regenerative medicine.