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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. [Display omitted] • A generalizable and effective mitosis detection algorithm to fully consider the mismatch across domains. • We transform the mitosis detection task into a semantic segmentation one to achieve precise mitotic figure identification. • An attention mechanism is utilized to generate channel-wise multi-scale features, which helps the network to extract more robust features. • An unsupervised Fourier-based data augmentation is used to align the domain discrepancies. • Our method won first place in the 2021 MIDOG challenge and showed successful generalization to unseen independent multicenter datasets. [ABSTRACT FROM AUTHOR]

Benefiting from the large-scale archiving of digitized whole-slide images (WSIs), computer-aided diagnosis has been well developed to assist pathologists in decision-making. Content-based WSI retrieval can be a new approach to find highly correlated WSIs in a historically diagnosed WSI archive, which has the potential usages for assisted clinical diagnosis, medical research, and trainee education. During WSI retrieval, it is particularly challenging to encode the semantic content of histopathological images and to measure the similarity between images for interpretable results due to the gigapixel size of WSIs. In this work, we propose a Retrieval with Clustering-guided Contrastive Learning (RetCCL) framework for robust and accurate WSI-level image retrieval, which integrates a novel self-supervised feature learning method and a global ranking and aggregation algorithm for much improved performance. The proposed feature learning method makes use of existing large-scale unlabeled histopathological image data, which helps learn universal features that could be used directly for subsequent WSI retrieval tasks without extra fine-tuning. The proposed WSI retrieval method not only returns a set of WSIs similar to a query WSI, but also highlights patches or sub-regions of each WSI that share high similarity with patches of the query WSI, which helps pathologists interpret the searching results. Our WSI retrieval framework has been evaluated on the tasks of anatomical site retrieval and cancer subtype retrieval using over 22,000 slides, and the performance exceeds other state-of-the-art methods significantly (around 10% for the anatomic site retrieval in terms of average m M V @ 10). Besides, the patch retrieval using our learned feature representation offers a performance improvement of 24% on the TissueNet dataset in terms of m M V @ 5 compared with using ImageNet pre-trained features, which further demonstrates the effectiveness of the proposed CCL feature learning method. [Display omitted] • A novel WSI retrieval algorithm called RetCCL is proposed. • RetCCL provides interpretable results by highlighting relevant sub-regions. • Our feature extractor (CCL) contains a weighted InfoNCE and a group-level InfoNCE. • CCL is pretrained using a large and diverse database of histopathological images. • CCL outperforms ImageNet-pretrained features or other SSL-based features. • RetCCL shows state-of-the-art WSI retrieval results. [ABSTRACT FROM AUTHOR]

A large-scale and well-annotated dataset is a key factor for the success of deep learning in medical image analysis. However, assembling such large annotations is very challenging, especially for histopathological images with unique characteristics (e.g., gigapixel image size, multiple cancer types, and wide staining variations). To alleviate this issue, self-supervised learning (SSL) could be a promising solution that relies only on unlabeled data to generate informative representations and generalizes well to various downstream tasks even with limited annotations. In this work, we propose a novel SSL strategy called semantically-relevant contrastive learning (SRCL), which compares relevance between instances to mine more positive pairs. Compared to the two views from an instance in traditional contrastive learning, our SRCL aligns multiple positive instances with similar visual concepts, which increases the diversity of positives and then results in more informative representations. We employ a hybrid model (CTransPath) as the backbone, which is designed by integrating a convolutional neural network (CNN) and a multi-scale Swin Transformer architecture. The CTransPath is pretrained on massively unlabeled histopathological images that could serve as a collaborative local–global feature extractor to learn universal feature representations more suitable for tasks in the histopathology image domain. The effectiveness of our SRCL-pretrained CTransPath is investigated on five types of downstream tasks (patch retrieval, patch classification, weakly-supervised whole-slide image classification, mitosis detection, and colorectal adenocarcinoma gland segmentation), covering nine public datasets. The results show that our SRCL-based visual representations not only achieve state-of-the-art performance in each dataset, but are also more robust and transferable than other SSL methods and ImageNet pretraining (both supervised and self-supervised methods). Our code and pretrained model are available at https://github.com/Xiyue-Wang/TransPath. [Display omitted] • The first Transformer-based unsupervised feature extractor for histopathological images. • A semantically-relevant contrastive learning approach is proposed. • A hybrid backbone (CTransPath) is constructed by combining CNN and Transformer. • CTransPath could be a general-purpose feature extractor for histopathological images. [ABSTRACT FROM AUTHOR]