Frozen sectioning (FS) is the preparation method of choice for microscopic evaluation of tissues during surgical operations. The high speed of the procedure allows pathologists to rapidly assess the key microscopic features, such as tumour margins and malignant status to guide surgical decision-making and minimise disruptions to the course of the operation. However, FS is prone to introducing many misleading artificial structures (histological artefacts), such as nuclear ice crystals, compression, and cutting artefacts, hindering timely and accurate diagnostic judgement of the pathologist. Additional training and prolonged experience is often required to make highly effective and time-critical diagnosis on frozen sections. On the other hand, the gold standard tissue preparation technique of formalin-fixation and paraffin-embedding (FFPE) provides significantly superior image quality, but is a very time-consuming process (12-48 hours), making it unsuitable for intra-operative use. In this paper, we propose an artificial intelligence (AI) method that improves FS image quality by computationally transforming frozen-sectioned whole-slide images (FS-WSIs) into whole-slide FFPE-style images in minutes. AI-FFPE rectifies FS artefacts with the guidance of an attention mechanism that puts a particular emphasis on artefacts while utilising a self-regularization mechanism established between FS input image and synthesized FFPE-style image that preserves clinically relevant features. As a result, AI-FFPE method successfully generates FFPE-style images without significantly extending tissue processing time and consequently improves diagnostic accuracy. We demonstrate the efficacy of AI-FFPE on lung and brain frozen sections using a variety of different qualitative and quantitative metrics including visual Turing tests from 20 board certified pathologists.
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