Computational pathology targets the automatic analysis of Whole Slide Images (WSI). WSIs are high-resolution digitized histopathology images, stained with chemical reagents to highlight specific tissue structures and scanned via whole slide scanners. The application of different parameters during WSI acquisition may lead to stain color heterogeneity, especially considering samples collected from several medical centers. Dealing with stain color heterogeneity often limits the robustness of methods developed to analyze WSIs, in particular Convolutional Neural Networks (CNN), the state-of-the-art algorithm for most computational pathology tasks. Stain color heterogeneity is still an unsolved problem, although several methods have been developed to alleviate it, such as Hue-Saturation-Contrast (HSC) color augmentation and stain augmentation methods. The goal of this paper is to present Data-Driven Color Augmentation (DDCA), a method to improve the efficiency of color augmentation methods by increasing the reliability of the samples used for training computational pathology models. During CNN training, a database including over 2 million H&E color variations collected from private and public datasets is used as a reference to discard augmented data with color distributions that do not correspond to realistic data. DDCA is applied to HSC color augmentation, stain augmentation and H&E-adversarial networks in colon and prostate cancer classification tasks. DDCA is then compared with 11 state-of-the-art baseline methods to handle color heterogeneity, showing that it can substantially improve classification performance on unseen data including heterogeneous color variations. 

https://doi.org/10.1016/j.jpi.2022.100183

Data-driven color augmentation for H&E stained images in computational pathology

Exa-scale volumes of medical data have been produced for decades. In most cases, the diagnosis is reported in free text, encoding medical knowledge that is still largely unexploited. In order to allow decoding medical knowledge included in reports, we propose an unsupervised knowledge extraction system combining a rule-based expert system with pre-trained Machine Learning (ML) models, namely the Semantic Knowledge Extractor Tool (SKET). Combining rule-based techniques and pre-trained ML models provides high accuracy results for knowledge extraction. This work demonstrates the viability of unsupervised Natural Language Processing (NLP) techniques to extract critical information from cancer reports, opening opportunities such as data mining for knowledge extraction purposes, precision medicine applications, structured report creation, and multimodal learning. SKET is a practical and unsupervised approach to extracting knowledge from pathology reports, which opens up unprecedented opportunities to exploit textual and multimodal medical information in clinical practice. We also propose SKET eXplained (SKET X), a web-based system providing visual explanations about the algorithmic decisions taken by SKET. SKET X is designed/developed to support pathologists and domain experts in understanding SKET predictions, possibly driving further improvements to the system. 

https://doi.org/10.1016/j.jpi.2022.100139

Empowering digital pathology applications through explainable knowledge extraction tools

Interpretability of deep learning is widely used to evaluate the reliability of medical imaging models and reduce the risks of inaccurate patient recommendations. For models exceeding human performance, e.g. predicting RNA structure from microscopy images, interpretable modelling can be further used to uncover highly non-trivial patterns which are otherwise imperceptible to the human eye. We show that interpretability can reveal connections between the microscopic appearance of cancer tissue and its gene expression profiling. While exhaustive profiling of all genes from the histology images is still challenging, we estimate the expression values of a well-known subset of genes that is indicative of cancer molecular subtype, survival, and treatment response in colorectal cancer. Our approach successfully identifies meaningful information from the image slides, highlighting hotspots of high gene expression. Our method can help characterise how gene expression shapes tissue morphology and this may be beneficial for patient stratification in the pathology unit. The code is available on GitHub.

Attention-based Interpretable Regression of Gene Expression in Histology

Interpretability of deep learning is widely used to evaluate the reliability of medical imaging models and reduce the risks of inaccurate patient recommendations. For models exceeding human performance, e.g. predicting RNA structure from microscopy images, interpretable modelling can be further used to uncover highly non-trivial patterns which are otherwise imperceptible to the human eye. We show that interpretability can reveal connections between the microscopic appearance of cancer tissue and its gene expression profiling. While exhaustive profiling of all genes from the histology images is still challenging, we estimate the expression values of a well-known subset of genes that is indicative of cancer molecular subtype, survival, and treatment response in colorectal cancer. Our approach successfully identifies meaningful information from the image slides, highlighting hotspots of high gene expression. Our method can help characterise how gene expression shapes tissue morphology and this may be beneficial for patient stratification in the pathology unit. The code is available on GitHub. 

/pdf/attention-based-interpretable-regression-of-gene-expression-1xtjz2na.pdf

Attention-Based Interpretable Regression of Gene Expression in Histology

Interpretable classification of pathology whole-slide images using attention based context-aware graph convolutional neural network

The digitalization of clinical workflows and the increasing performance of deep learning algorithms are paving the way towards new methods for tackling cancer diagnosis. However, the availability of medical specialists to annotate digitized images and free-text diagnostic reports does not scale with the need for large datasets required to train robust computer-aided diagnosis methods that can target the high variability of clinical cases and data produced. This work proposes and evaluates an approach to eliminate the need for manual annotations to train computer-aided diagnosis tools in digital pathology. The approach includes two components, to automatically extract semantically meaningful concepts from diagnostic reports and use them as weak labels to train convolutional neural networks (CNNs) for histopathology diagnosis. The approach is trained (through 10-fold cross-validation) on 3'769 clinical images and reports, provided by two hospitals and tested on over 11'000 images from private and publicly available datasets. The CNN, trained with automatically generated labels, is compared with the same architecture trained with manual labels. Results show that combining text analysis and end-to-end deep neural networks allows building computer-aided diagnosis tools that reach solid performance (micro-accuracy = 0.908 at image-level) based only on existing clinical data without the need for manual annotations. 

/pdf/unleashing-the-potential-of-digital-pathology-data-by-1i9k6mzx.pdf

Edyta Petters

Papers

Unleashing the potential of digital pathology data by training computer-aided diagnosis models without human annotations