Improving CNN-Based Mitosis Detection through Rescanning Annotated Glass Slides and Atypical Mitosis Subtyping

Rutger RH Fick, Christof Bertram, Marc Aubreville

Keywords: Whole Slide Imaging, Mitosis Detection, Atypical Mitosis Subtyping, Deep Learning

Abstract:

The identification of mitotic figures (MFs) is a routine task in the histopathological assessment of tumor malignancy with known limitations for human observers. For a machine learning pipeline to robustly detect MFs, it must overcome a variety of conditions such as different scanners, staining protocols, tissue configurations, and organ types.
In order to develop a deep learning-based algorithm that can cope with these challenges, there are two obstacles that need to be overcome: obtaining a large-scale dataset of MF annotations spread across different domains of interest, including whole slide images (WSIs) exhaustively annotated for MFs, and using the annotated MFs in an efficient training process to extract the most relevant features for classification.
Our work attempts to address both of these challenges and establishes an MF detection pipeline trained solely on animal data, yet competitive on the mixed human/animal MIDOG22 dataset, and, in particular, on human breast cancer.
First, we propose a processing pipeline that allows us to strengthen the true scanner robustness of our dataset by physically rescanning the glass slides of annotated WSIs and registering MF positions. To enable the use of such rescans for training, we propose a novel learning paradigm tailored for labels that match partially, which allows to account for ambiguous MF positions in the rescans caused by spurious, suboptimal fine-focus on potential MFs by the scanner. Second, we demonstrate how a multi-task learning approach for MF subtypes, including the prediction of atypical mitotic figures (AMFs), can significantly enhance a model's ability to distinguish MFs from imposters. Our algorithm, using a standard object detection pipeline, performs very competitively with an average test set F1 value across five runs of 0.80 on the MIDOG22 training set. We also demonstrate its ability to stratify overall survival on the TCGA-BRCA dataset based on mitotic density, though it falls short of reaching significance in stratifying survival based on AMFs.

Submission Number: 138