Noninvasive Nonlinear Optical Computational Histology

Cancer remains a global health challenge, demanding early detection and accurate diagnosis for improved patient outcomes. An intelligent paradigm is introduced that elevates label-free nonlinear optical imaging with contrastive patch-wise learning, yielding stain-free nonlinear optical computational histology (NOCH). NOCH enables swift, precise diagnostic analysis of fresh tissues, reducing patient anxiety and healthcare costs. Nonlinear modalities are evaluated, including stimulated Raman scattering and multiphoton imaging, for their ability to enhance tumor microenvironment sensitivity, pathological analysis, and cancer examination. Quantitative analysis confirmed that NOCH images accurately reproduce nuclear morphometric features across different cancer stages. Key diagnostic features, such as nuclear morphology, size, and nuclear-cytoplasmic contrast, are well preserved. NOCH models also demonstrate promising generalization when applied to other pathological tissues. The study unites label-free nonlinear optical imaging with histopathology using contrastive learning to establish stain-free computational histology. NOCH provides a rapid, non-invasive, and precise approach to surgical pathology, holding immense potential for revolutionizing cancer diagnosis and surgical interventions. This paper presents stain-free nonlinear optical computational histology (NOCH) for rapid, non-invasive fresh tissue analysis. By fusing rich intrinsic signals of nonlinear optical imaging with tailored contrastive deep learning, NOCH digitally stains label-free images into realistic virtual histological slides. Quantitative validations across different cancer types and stages confirm accurate reproduction of essential pathological features, providing histopathology without cumbersome staining workflows.image