Abstract

Advanced digital control of microscopes and programmable data acquisition workflows have become increasingly important for improving the throughput and reproducibility of optical imaging experiments. Combinations of imaging modalities have enabled a more comprehensive understanding of tissue biology and tumor microenvironments in histopathological studies. However, insufficient imaging throughput and complicated workflows still limit the scalability of multimodal histopathology imaging. We present a hardware-software co-design of a whole slide scanning system for high-throughput multimodal tissue imaging, including brightfield (BF) and laser scanning microscopy. The system can automatically detect regions of interest using deep neural networks in a low-magnification rapid BF scan of the tissue slide and then conduct high-resolution BF scanning and laser scanning imaging on targeted regions with deep learning-based run-time denoising and resolution enhancement. The acquisition workflow is built using Pycro-Manager, a Python package that bridges hardware control libraries of the Java-based open-source microscopy software Micro-Manager in a Python environment. The system can achieve optimized imaging settings for both modalities with minimized human intervention and speed up the laser scanning by an order of magnitude with run-time image processing. The system integrates the acquisition pipeline and data analysis pipeline into a single workflow that improves the throughput and reproducibility of multimodal histopathological imaging.

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