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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.

Pathological features are the gold standard for tumor diagnosis, guiding treatment and prognosis. However, standard histopathological process is labor-intensive and time-consuming, while frozen sections have lower accuracy. Dynamic full-field optical coherence tomography (D-FFOCT) offers rapid histologic information by measuring the subcellular dynamics of fresh, unprocessed tissues. However, D-FFOCT images suffer from abrupt shifts in hue and brightness, which is confusing for pathologists and diminish their interpretability and reliability. Here, we present active phase modulation-assisted D-FFOCT (APMD-FFOCT) to improve the imaging stability and enhance the contrast of static tissues. This enables us to further employ an unsupervised deep learning to convert APMD-FFOCT images into virtual hematoxylin and eosin (H&E) stained images for the first time. Three-dimensional (3D) virtual H&E-stained images have been obtained at a scanning rate of 1 frame per second, as demonstrated in cancer diagnosis for human central nervous system and breast. The results prove that this new method will play a unique and important role in intraoperative histology.