From What to Why, the Growing Need for a Focus Shift Toward Explainability of AI in Digital Pathology

While it is impossible to deny the performance gains achieved through the incorporation of deep learning (DL) and other artificial intelligence (AI)-based techniques in pathology, minimal work has been done to answer the crucial question of why these algorithms predict what they predict. Tracing back classification decisions to specific input features allows for the quick identification of model bias as well as providing additional information toward understanding underlying biological mechanisms. In digital pathology, increasing the explainability of AI models would have the largest and most immediate impact for the image classification task. In this review, we detail some considerations that should be made in order to develop models with a focus on explainability.

Integrating morphologic and molecular histopathological features through whole slide image registration and deep learning

Background Modern molecular pathology workflows in neuro-oncology heavily rely on the integration of morphologic and immunohistochemical patterns for analysis, classification, and prognostication. However, despite the recent emergence of digital pathology platforms and artificial intelligence-driven computational image analysis tools, automating the integration of histomorphologic information found across these multiple studies is challenged by large files sizes of whole slide images (WSIs) and shifts/rotations in tissue sections introduced during slide preparation. Methods To address this, we develop a workflow that couples different computer vision tools including scale-invariant feature transform (SIFT) and deep learning to efficiently align and integrate histopathological information found across multiple independent studies. We highlight the utility and automation potential of this workflow in the molecular subclassification and discovery of previously unappreciated spatial patterns in diffuse gliomas. Results First, we show how a SIFT-driven computer vision workflow was effective at automated WSI alignment in a cohort of 107 randomly selected surgical neuropathology cases (97/107 (91%) showing appropriate matches, AUC = 0.96). This alignment allows our AI-driven diagnostic workflow to not only differentiate different brain tumor types, but also integrate and carry out molecular subclassification of diffuse gliomas using relevant immunohistochemical biomarkers (IDH1-R132H, ATRX). To highlight the discovery potential of this workflow, we also examined spatial distributions of tumors showing heterogenous expression of the proliferation marker MIB1 and Olig2. This analysis helped uncovered an interesting and unappreciated association of Olig2 positive and proliferative areas in some gliomas (r = 0.62). Conclusion This efficient neuropathologist-inspired workflow provides a generalizable approach to help automate a variety of advanced immunohistochemically compatible diagnostic and discovery exercises in surgical neuropathology and neuro-oncology.

ARTIFICIAL INTELLIGENCE AND NEXT GENERATION PATHOLOGY: TOWARDS PERSONALIZED MEDICINE

Introduction. Over the past few decades, thanks to advances in algorithm development, the introduction of available computing power, and the management of large data sets, machine learning methods have become active in various fields of life. Among them, deep learning possesses a special place, which is used in many spheres of health care and is an integral part and prerequisite for the development of digital pathology. Objectives. The purpose of the review was to gather the data on existing image analysis technologies and machine learning tools developed for the whole-slide digital images in pathology. Methods: Analysis of the literature on machine learning methods used in pathology, staps of automated image analysis, types of neural networks, their application and capabilities in digital pathology was performed. Results. To date, a wide range of deep learning strategies have been developed, which are actively used in digital pathology, and demonstrated excellent diagnostic accuracy. In addition to diagnostic solutions, the integration of artificial intelligence into the practice of pathomorphological laboratory provides new tools for assessing the prognosis and prediction of sensitivity to different treatments. Conclusions: The synergy of artificial intelligence and digital pathology is a key tool to improve the accuracy of diagnostics, prognostication and personalized medicine facilitation

The future of artificial intelligence in digital pathology - results of a survey across stakeholder groups

Artificial intelligence (AI) provides a powerful tool to extract information from digitized histopathology whole slide images. In the last five years, academic and commercial actors have developed new technical solutions for a diverse set of tasks, including tissue segmentation, cell detection, mutation prediction, prognostication and prediction of treatment response. In the light of limited overall resources, it is presently unclear for researchers, practitioners and policymakers which of these topics are stable enough for clinical use in the near future and which topics are still experimental, but worth investing time and effort into. To identify potentially promising applications of AI in pathology, we performed an anonymous online survey of 75 computational pathology domain experts from academia and industry. Participants enrolled in 2021 were queried about their subjective opinion on promising and appealing sub-fields of computational pathology with a focus on solid tumors. The results of this survey indicate that the prediction of treatment response directly from routine pathology slides is regarded as the most promising future application. This item was ranked highest in the overall analysis and in sub-groups by age and professional background. Furthermore, prediction of genetic alterations, gene expression and survival directly from routine pathology images scored consistently high across subgroups. Together, these data demonstrate a possible direction for the development of computational pathology systems in clinical, academic and industrial research in the near future.