Label-free intravital optical imaging, and imaging of fresh, unstained, resected tissue specimens, offer a wealth of new biomarkers for revealing the true colors of cancer and for diagnosing disease. Using new fiber-laser-pumped photonic crystal fiber source technology and nonlinear optics to generate new excitation wavelengths and manipulate the light stimulus in new ways, Simultaneous Label-free Auto-fluorescence Multi-harmonic (SLAM) microscopy can achieve fast simultaneous visualization of not only architectural features, but also the rich intrinsic molecular and metabolic features within tissues. Quantitative machine/deep learning analyses of these multi-dimensional datasets can be used to identify selective biomarkers for cancer, such as cancer-associated extracellular vesicles. The clinical demonstration of these optical biomedical imaging technologies offers new paradigms for point-of-procedure diagnosis and guidance.
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