Péter Bándi

Péter Bándi, Maschenka Balkenhol, Marcory van Dijk et al.

Recently, large, high-quality public datasets have led to the development of convolutional neural networks that can detect lymph node metastases of breast cancer at the level of expert pathologists. Many cancers, regardless of the site of origin, can metastasize to lymph nodes. However, collecting and annotating high-volume, high-quality datasets for every cancer type is challenging. In this paper we investigate how to leverage existing high-quality datasets most efficiently in multi-task settings for closely related tasks. Specifically, we will explore different training and domain adaptation strategies, including prevention of catastrophic forgetting, for colon and head-and-neck cancer metastasis detection in lymph nodes. Our results show state-of-the-art performance on both cancer metastasis detection tasks. Furthermore, we show the effectiveness of repeated adaptation of networks from one cancer type to another to obtain multi-task metastasis detection networks. Last, we show that leveraging existing high-quality datasets can significantly boost performance on new target tasks and that catastrophic forgetting can be effectively mitigated using regularization.

David Tellez, Geert Litjens, Peter Bandi et al.

Stain variation is a phenomenon observed when distinct pathology laboratories stain tissue slides that exhibit similar but not identical color appearance. Due to this color shift between laboratories, convolutional neural networks (CNNs) trained with images from one lab often underperform on unseen images from the other lab. Several techniques have been proposed to reduce the generalization error, mainly grouped into two categories: stain color augmentation and stain color normalization. The former simulates a wide variety of realistic stain variations during training, producing stain-invariant CNNs. The latter aims to match training and test color distributions in order to reduce stain variation. For the first time, we compared some of these techniques and quantified their effect on CNN classification performance using a heterogeneous dataset of hematoxylin and eosin histopathology images from 4 organs and 9 pathology laboratories. Additionally, we propose a novel unsupervised method to perform stain color normalization using a neural network. Based on our experimental results, we provide practical guidelines on how to use stain color augmentation and stain color normalization in future computational pathology applications.

Wouter Bulten, Péter Bándi, Jeffrey Hoven et al.

Prostate cancer (PCa) is graded by pathologists by examining the architectural pattern of cancerous epithelial tissue on hematoxylin and eosin (H&E) stained slides. Given the importance of gland morphology, automatically differentiating between glandular epithelial tissue and other tissues is an important prerequisite for the development of automated methods for detecting PCa. We propose a new method, using deep learning, for automatically segmenting epithelial tissue in digitized prostatectomy slides. We employed immunohistochemistry (IHC) to render the ground truth less subjective and more precise compared to manual outlining on H&E slides, especially in areas with high-grade and poorly differentiated PCa. Our dataset consisted of 102 tissue blocks, including both low and high grade PCa. From each block a single new section was cut, stained with H&E, scanned, restained using P63 and CK8/18 to highlight the epithelial structure, and scanned again. The H&E slides were co-registered to the IHC slides. On a subset of the IHC slides we applied color deconvolution, corrected stain errors manually, and trained a U-Net to perform segmentation of epithelial structures. Whole-slide segmentation masks generated by the IHC U-Net were used to train a second U-Net on H&E. Our system makes precise cell-level segmentations and segments both intact glands as well as individual (tumor) epithelial cells. We achieved an F1-score of 0.895 on a hold-out test set and 0.827 on an external reference set from a different center. We envision this segmentation as being the first part of a fully automated prostate cancer detection and grading pipeline.

Péter Bándi, Rob van de Loo, Milad Intezar et al.

Tissue segmentation is an important pre-requisite for efficient and accurate diagnostics in digital pathology. However, it is well known that whole-slide scanners can fail in detecting all tissue regions, for example due to the tissue type, or due to weak staining because their tissue detection algorithms are not robust enough. In this paper, we introduce two different convolutional neural network architectures for whole slide image segmentation to accurately identify the tissue sections. We also compare the algorithms to a published traditional method. We collected 54 whole slide images with differing stains and tissue types from three laboratories to validate our algorithms. We show that while the two methods do not differ significantly they outperform their traditional counterpart (Jaccard index of 0.937 and 0.929 vs. 0.870, p < 0.01).