AV-GAN: Attention-Based Varifocal Generative Adversarial Network for Uneven Medical Image Translation

Different types of staining highlight different structures in organs, thereby assisting in diagnosis. However, due to the impossibility of repeated staining, we cannot obtain different types of stained slides of the same tissue area. Translating the slide that is easy to obtain (e.g., H&E) to slides of staining types difficult to obtain (e.g., MT, PAS) is a promising way to solve this problem. However, some regions are closely connected to other regions, and to maintain this connection, they often have complex structures and are difficult to translate, which may lead to wrong translations. In this paper, we propose the Attention-Based Varifocal Generative Adversarial Network (AV-GAN), which solves multiple problems in pathologic image translation tasks, such as uneven translation difficulty in different regions, mutual interference of multiple resolution information, and nuclear deformation. Specifically, we develop an Attention-Based Key Region Selection Module, which can attend to regions with higher translation difficulty. We then develop a Varifocal Module to translate these regions at multiple resolutions. Experimental results show that our proposed AV-GAN outperforms existing image translation methods with two virtual kidney tissue staining tasks and improves FID values by 15.9 and 4.16 respectively in the H&E-MT and H&E-PAS tasks.

Deep Learning Predicts Biomarker Status and Discovers Related Histomorphology Characteristics for Low-Grade Glioma

Biomarker detection is an indispensable part in the diagnosis and treatment of low-grade glioma (LGG). However, current LGG biomarker detection methods rely on expensive and complex molecular genetic testing, for which professionals are required to analyze the results, and intra-rater variability is often reported. To overcome these challenges, we propose an interpretable deep learning pipeline, a Multi-Biomarker Histomorphology Discoverer (Multi-Beholder) model based on the multiple instance learning (MIL) framework, to predict the status of five biomarkers in LGG using only hematoxylin and eosin-stained whole slide images and slide-level biomarker status labels. Specifically, by incorporating the one-class classification into the MIL framework, accurate instance pseudo-labeling is realized for instance-level supervision, which greatly complements the slide-level labels and improves the biomarker prediction performance. Multi-Beholder demonstrates superior prediction performance and generalizability for five LGG biomarkers (AUROC=0.6469-0.9735) in two cohorts (n=607) with diverse races and scanning protocols. Moreover, the excellent interpretability of Multi-Beholder allows for discovering the quantitative and qualitative correlations between biomarker status and histomorphology characteristics. Our pipeline not only provides a novel approach for biomarker prediction, enhancing the applicability of molecular treatments for LGG patients but also facilitates the discovery of new mechanisms in molecular functionality and LGG progression.