A generalizable and robust deep learning algorithm for mitosis detection in multicenter breast histopathological images

Mitosis counting of biopsies is an important biomarker for breast cancer patients, which supports disease prognostication and treatment planning. Developing a robust mitotic cell detection model is highly challenging due to its complex growth pattern and high similarities with non-mitotic cells. Most mitosis detection algorithms have poor generalizability across image domains and lack reproducibility and validation in multicenter settings. To overcome these issues, we propose a generalizable and robust mitosis detection algorithm (called FMDet), which is independently tested on multicenter breast histopathological images. To capture more refined morphological features of cells, we convert the object detection task as a semantic segmentation problem. The pixel-level annotations for mitotic nuclei are obtained by taking the intersection of the masks generated from a well-trained nuclear segmentation model and the bounding boxes provided by the MIDOG 2021 challenge. In our segmentation framework, a robust feature extractor is developed to capture the appearance variations of mitotic cells, which is constructed by integrating a channel-wise multi-scale attention mechanism into a fully convolutional network structure. Benefiting from the fact that the changes in the low-level spectrum do not affect the high-level semantic perception, we employ a Fourier-based data augmentation method to reduce domain discrepancies by exchanging the low-frequency spectrum between two domains. Our FMDet algorithm has been tested in the MIDOG 2021 challenge and ranked first place. Further, our algorithm is also externally validated on four independent datasets for mitosis detection, which exhibits state-of-the-art performance in comparison with previously published results. These results demonstrate that our algorithm has the potential to be deployed as an assistant decision support tool in clinical practice. Our code has been released at https://github.com/Xiyue-Wang/1st-in-MICCAI-MIDOG-2021-challenge.