Case-based similar image retrieval for weakly annotated large histopathological images of malignant lymphoma using deep metric learning

In the present study, we propose a novel case-based similar image retrieval (SIR) method for hematoxylin and eosin (H&E)-stained histopathological images of malignant lymphoma. When a whole slide image (WSI) is used as an input query, it is desirable to be able to retrieve similar cases by focusing on image patches in pathologically important regions such as tumor cells. To address this problem, we employ attention-based multiple instance learning, which enables us to focus on tumor-specific regions when the similarity between cases is computed. Moreover, we employ contrastive distance metric learning to incorporate immunohistochemical (IHC) staining patterns as useful supervised information for defining appropriate similarity between heterogeneous malignant lymphoma cases. In the experiment with 249 malignant lymphoma patients, we confirmed that the proposed method exhibited higher evaluation measures than the baseline case-based SIR methods. Furthermore, the subjective evaluation by pathologists revealed that our similarity measure using IHC staining patterns is appropriate for representing the similarity of H&E-stained tissue images for malignant lymphoma.

Multi-scale domain-adversarial multiple-instance CNN for cancer subtype classification with non-annotated histopathological images

We propose a new method for cancer subtype classification from histopathological images, which can automatically detect tumor-specific features in a given whole slide image (WSI). The cancer subtype should be classified by referring to a WSI, i.e., a large size image (typically 40,000x40,000 pixels) of an entire pathological tissue slide, which consists of cancer and non-cancer portions. One difficulty for constructing cancer subtype classifiers comes from the high cost needed for annotating WSIs; without annotation, we have to construct the tumor region detector without knowing true labels. Furthermore, both global and local image features must be extracted from the WSI by changing the magnifications of the image. In addition, the image features should be stably detected against the variety/difference of staining among the hospitals/specimen. In this paper, we develop a new CNN-based cancer subtype classification method by effectively combining multiple-instance, domain adversarial, and multi-scale learning frameworks that can overcome these practical difficulties. When the proposed method was applied to malignant lymphoma subtype classifications of 196 cases collected from multiple hospitals, the classification performance was significantly better than the standard CNN or other conventional methods, and the accuracy was favorably compared to that of standard pathologists. In addition, we confirmed by immunostaining and expert pathologist's visual inspections that the tumor regions were correctly detected.