High-resolution label-free imaging of tissue morphology with confocal phase microscopy

Abstract

Label-free imaging approaches seek to simplify and augment histopathologic assessment by replacing the current practice of staining by dyes to visualize tissue morphology with quantitative optical measurements. Quantitative phase imaging (QPI) operates with visible/UV light and thus provides a resolution matched to current practice. Here we introduce and demonstrate confocal QPI for label-free imaging of tissue sections and assess its utility for manual histopathologic inspection. Imaging cancerous and normal adjacent human breast and prostate, we show that tissue structural organization can be resolved with high spatial detail comparable to conventional H&E stains. Our confocal QPI images are found to be free of halo, solving this common problem in QPI. We further describe and apply a virtual imaging system based on Finite-Difference Time-Domain (FDTD) calculations to quantitatively compare confocal with wide-field QPI methods and explore performance limits using numerical tissue phantoms.

arXiv comment18 pages, 6 figures

References in corpus (4)

• Phase recovery and holographic image reconstruction using deep learning in neural networks
• HoloStain: Holographic virtual staining of individual biological cells
• Structured illumination multimodal 3D-resolved quantitative phase and fluorescence sub-diffraction microscopy
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Cited by in corpus (4)

• Artificial confocal microscopy for deep label-free imaging
• Synthetic aperture interference light (SAIL) microscopy for high-throughput label-free imaging
• Experimental verification of field-enhanced molecular vibrational scattering at single infrared antennas
• Computational refocusing in phase-resolved confocal microscopy