Mitosis domain generalization in histopathology images - The MIDOG challenge.

The density of mitotic figures (MF) within tumor tissue is known to be highly correlated with tumor proliferation and thus is an important marker in tumor grading. Recognition of MF by pathologists is subject to a strong inter-rater bias, limiting its prognostic value. State-of-the-art deep learning methods can support experts but have been observed to strongly deteriorate when applied in a different clinical environment. The variability caused by using different whole slide scanners has been identified as one decisive component in the underlying domain shift. The goal of the MICCAI MIDOG 2021 challenge was the creation of scanner-agnostic MF detection algorithms. The challenge used a training set of 200 cases, split across four scanning systems. As test set, an additional 100 cases split across four scanning systems, including two previously unseen scanners, were provided. In this paper, we evaluate and compare the approaches that were submitted to the challenge and identify methodological factors contributing to better performance. The winning algorithm yielded an F1 score of 0.748 (CI95: 0.704-0.781), exceeding the performance of six experts on the same task.

MiNuGAN: Dual Segmentation of Mitoses and Nuclei Using Conditional GANs on Multi-center Breast H&E Images.

Breast cancer is the second most commonly diagnosed type of cancer among women as of 2021. Grading of histopathological images is used to guide breast cancer treatment decisions and a critical component of this is a mitotic score, which is related to tumor aggressiveness. Manual mitosis counting is an extremely tedious manual task, but automated approaches can be used to overcome inefficiency and subjectivity. In this paper, we propose an automatic mitosis and nuclear segmentation method for a diverse set of H&E breast cancer pathology images. The method is based on a conditional generative adversarial network to segment both mitoses and nuclei at the same time. Architecture optimizations are investigated, including hyper parameters and the addition of a focal loss. The accuracy of the proposed method is investigated using images from multiple centers and scanners, including TUPAC16, ICPR14 and ICPR12 datasets. In TUPAC16, we use 618 carefully annotated images of size 256×256 scanned at 40×. TUPAC16 is used to train the model, and segmentation performance is measured on the test set for both nuclei and mitoses. Results on 200 held-out testing images from the TUPAC16 dataset were mean DSC = 0.784 and 0.721 for nuclear and mitosis, respectively. On 202 ICPR12 images, mitosis segmentation accuracy had a mean DSC = 0.782, indicating the model generalizes well to unseen datasets. For datasets that had mitosis centroid annotations, which included 200 TUPAC16, 202 ICPR12 and 524 ICPR14, a mean F1-score of 0.854 was found indicating high mitosis detection accuracy.

Automated segmentation of cell membranes to evaluate HER2 status in whole slide images using a modified deep learning network.

The uncontrollable growth of cells in the breast tissue causes breast cancer which is the second most common type of cancer affecting women in the United States. Normally, human epidermal growth factor receptor 2 (HER2) proteins are responsible for the division and growth of healthy breast cells. HER2 status is currently assessed using immunohistochemistry (IHC) as well as in situ hybridization (ISH) in equivocal cases. Manual HER2 evaluation of IHC stained microscopic images involves an error-prone, tedious, inter-observer variable, and time-consuming routine lab work due to diverse staining, overlapped regions, and non-homogeneous remarkable large slides. To address these issues, digital pathology offers reproducible, automatic, and objective analysis and interpretation of whole slide image (WSI). In this paper, we present a machine learning (ML) framework to segment, classify, and quantify IHC breast cancer images in an effective way. The proposed method consists of two major classifying and segmentation parts. Since HER2 is associated with tumors of an epithelial region and most of the breast tumors originate in epithelial tissue, it is crucial to develop an approach to segment different tissue structures. The proposed technique is comprised of three steps. In the first step, a superpixel-based support vector machine (SVM) feature learning classifier is proposed to classify epithelial and stromal regions from WSI. In the second stage, on classified epithelial regions, a convolutional neural network (CNN) based segmentation method is applied to segment membrane regions. Finally, divided tiles are merged and the overall score of each slide is evaluated. Experimental results for 127 slides are presented and compared with state-of-the-art handcraft and deep learning-based approaches. The experiments demonstrate that the proposed method achieved promising performance on IHC stained data. The presented automated algorithm was shown to outperform other approaches in terms of superpixel based classifying of epithelial regions and segmentation of membrane staining using CNN.