Deep Learning-Based Prediction of Molecular Tumor Biomarkers from H&E: A Practical Review

Molecular and genomic properties are critical in selecting cancer treatments to target individual tumors, particularly for immunotherapy. However, the methods to assess such properties are expensive, time-consuming, and often not routinely performed. Applying machine learning to H&E images can provide a more cost-effective screening method. Dozens of studies over the last few years have demonstrated that a variety of molecular biomarkers can be predicted from H&E alone using the advancements of deep learning: molecular alterations, genomic subtypes, protein biomarkers, and even the presence of viruses. This article reviews the diverse applications across cancer types and the methodology to train and validate these models on whole slide images. From bottom-up to pathologist-driven to hybrid approaches, the leading trends include a variety of weakly supervised deep learning-based approaches, as well as mechanisms for training strongly supervised models in select situations. While results of these algorithms look promising, some challenges still persist, including small training sets, rigorous validation, and model explainability. Biomarker prediction models may yield a screening method to determine when to run molecular tests or an alternative when molecular tests are not possible. They also create new opportunities in quantifying intratumoral heterogeneity and predicting patient outcomes.Comment: 20 pages, 2 figure

On Edge Computing for Remote Pathology Consultations and Computations

Telepathology aims to replace the pathology operations performed on-site, but current systems are limited by their prohibitive cost, or by the adopted underlying technologies. In this work, we contribute to overcoming these limitations by bringing the recent advances of edge computing to reduce latency and increase local computation abilities to the pathology ecosystem. In particular, this paper presents LiveMicro, a system whose benefit is twofold: on one hand, it enables edge computing driven digital pathology computations, such as data-driven image processing on a live capture of the microscope. On the other hand, our system allows remote pathologists to diagnosis in collaboration in a single virtual microscope session, facilitating continuous medical education and remote consultation, crucial for under-served and remote hospital or private practice. Our results show the benefits and the principles underpinning our solution, with particular emphasis on how the pathologists interact with our application. Additionally, we developed simple yet effective diagnosis-aided algorithms to demonstrate the practicality of our approach

Simplified three-dimensional tissue clearing and incorporation of colorimetric phenotyping.

Tissue clearing methods promise to provide exquisite three-dimensional imaging information; however, there is a need for simplified methods for lower resource settings and for non-fluorescence based phenotyping to enable light microscopic imaging modalities. Here we describe the simplified CLARITY method (SCM) for tissue clearing that preserves epitopes of interest. We imaged the resulting tissues using light sheet microscopy to generate rapid 3D reconstructions of entire tissues and organs. In addition, to enable clearing and 3D tissue imaging with light microscopy methods, we developed a colorimetric, non-fluorescent method for specifically labeling cleared tissues based on horseradish peroxidase conversion of diaminobenzidine to a colored insoluble product. The methods we describe here are portable and can be accomplished at low cost, and can allow light microscopic imaging of cleared tissues, thus enabling tissue clearing and imaging in a wide variety of settings