Dual-modality, deep-learning-enabled endomicroscope with large field-of-view and depth-of-field for real-time in vivo imaging of epithelial hallmarks of cancer

Abstract In vivo microscopy (IVM) has shown great promise to improve early detection of epithelial precancer, but it suffers from fundamental trade-offs that limit the resolution, field-of-view (FOV) and depth-of-field (DOF). Here, we present PrecisionView, a compact, deep-learning-enabled endomicroscope that breaks these constrains and achieves 20 mm 2 FOV and 500 µm DOF with 4 µm resolution, representing approximately 5× increase in FOV and 8× larger DOF compared to conventional IVM with similar resolution. PrecisionView integrates a deep-learning optimized phase mask and real-time reconstruction, enabling rapid in vivo assessment of two key hallmarks of cancer: epithelial cell nuclear morphology and subsurface microvasculature through fluorescence and reflectance imaging. By imaging oral cavity of healthy volunteers and cervical specimens with precancerous lesions, PrecisionView generates large-scale (1-3 cm 2 ) co-registered maps of cellular and vascular structures, revealing distinct microscopic patterns associated with anatomic structures and precancerous lesions. Our results suggest the potential of this computational endomicroscope to address the unmet need for early cancer detection at the point-of-care.