Maria A. Hawkins

Zhuoyan Shen, Mikael Simard, Douglas Brand et al.

Mitotic activity is an important feature for grading several cancer types. Counting mitotic figures (MFs) is a time-consuming, laborious task prone to inter-observer variation. Inaccurate recognition of MFs can lead to incorrect grading and hence potential suboptimal treatment. In this study, we propose an artificial intelligence (AI)-aided approach to detect MFs in digitised haematoxylin and eosin-stained whole slide images (WSIs). Advances in this area are hampered by the limited number and types of cancer datasets of MFs. Here we establish the largest pan-cancer dataset of mitotic figures by combining an in-house dataset of soft tissue tumours (STMF) with five open-source mitotic datasets comprising multiple human cancers and canine specimens (ICPR, TUPAC, CCMCT, CMC and MIDOG++). This new dataset identifies 74,620 MFs and 105,538 mitotic-like figures. We then employed a two-stage framework (the Optimised Mitoses Generator Network (OMG-Net) to classify MFs. The framework first deploys the Segment Anything Model (SAM) to automate the contouring of MFs and surrounding objects. An adapted ResNet18 is subsequently trained to classify MFs. OMG-Net reaches an F1-score of 0.84 on pan-cancer MF detection (breast carcinoma, neuroendocrine tumour and melanoma), largely outperforming the previous state-of-the-art MIDOG++ benchmark model on its hold-out testing set (e.g. +16% F1-score on breast cancer detection, p<0.001) thereby providing superior accuracy in detecting MFs on various types of tumours obtained with different scanners.

Mikaël Simard, Zhuoyan Shen, Konstantin Bräutigam et al.

With the advent of novel cancer treatment options such as immunotherapy, studying the tumour immune micro-environment (TIME) is crucial to inform on prognosis and understand potential response to therapeutic agents. A key approach to characterising the TIME may be through combining (1) digitised microscopic high-resolution optical images of hematoxylin and eosin (H&E) stained tissue sections obtained in routine histopathology examinations with (2) automated immune cell detection and classification methods. In this work, we introduce a workflow to automatically generate robust single cell contours and labels from dually stained tissue sections with H&E and multiplexed immunofluorescence (IF) markers. The approach harnesses the Segment Anything Model and requires minimal human intervention compared to existing single cell databases. With this methodology, we create Immunocto, a massive, multi-million automatically generated database of 6,848,454 human cells and objects, including 2,282,818 immune cells distributed across 4 subtypes: CD4$^+$ T cell lymphocytes, CD8$^+$ T cell lymphocytes, CD20$^+$ B cell lymphocytes, and CD68$^+$/CD163$^+$ macrophages. For each cell, we provide a 64$\times$64 pixels$^2$ H&E image at $\mathbf{40}\times$ magnification, along with a binary mask of the nucleus and a label. The database, which is made publicly available, can be used to train models to study the TIME on routine H&E slides. We show that deep learning models trained on Immunocto result in state-of-the-art performance for lymphocyte detection. The approach demonstrates the benefits of using matched H&E and IF data to generate robust databases for computational pathology applications.