Multi-domain stain normalization for digital pathology: A cycle-consistent adversarial network for whole slide images.

The variation in histologic staining between different medical centers is one of the most profound challenges in the field of computer-aided diagnosis. The appearance disparity of pathological whole slide images causes algorithms to become less reliable, which in turn impedes the wide-spread applicability of downstream tasks like cancer diagnosis. Furthermore, different stainings lead to biases in the training which in case of domain shifts negatively affect the test performance. Therefore, in this paper we propose MultiStain-CycleGAN, a multi-domain approach to stain normalization based on CycleGAN. Our modifications to CycleGAN allow us to normalize images of different origins without retraining or using different models. We perform an extensive evaluation of our method using various metrics and compare it to commonly used methods that are multi-domain capable. First, we evaluate how well our method fools a domain classifier that tries to assign a medical center to an image. Then, we test our normalization on the tumor classification performance of a downstream classifier. Furthermore, we evaluate the image quality of the normalized images using the Structural similarity index and the ability to reduce the domain shift using the Fréchet inception distance. We show that our method proves to be multi-domain capable, provides a very high image quality among the compared methods, and can most reliably fool the domain classifier while keeping the tumor classifier performance high. By reducing the domain influence, biases in the data can be removed on the one hand and the origin of the whole slide image can be disguised on the other, thus enhancing patient data privacy.

Colorectal cancer risk stratification on histological slides based on survival curves predicted by deep learning.

Studies have shown that colorectal cancer prognosis can be predicted by deep learning-based analysis of histological tissue sections of the primary tumor. So far, this has been achieved using a binary prediction. Survival curves might contain more detailed information and thus enable a more fine-grained risk prediction. Therefore, we established survival curve-based CRC survival predictors and benchmarked them against standard binary survival predictors, comparing their performance extensively on the clinical high and low risk subsets of one internal and three external cohorts. Survival curve-based risk prediction achieved a very similar risk stratification to binary risk prediction for this task. Exchanging other components of the pipeline, namely input tissue and feature extractor, had largely identical effects on model performance independently of the type of risk prediction. An ensemble of all survival curve-based models exhibited a more robust performance, as did a similar ensemble based on binary risk prediction. Patients could be further stratified within clinical risk groups. However, performance still varied across cohorts, indicating limited generalization of all investigated image analysis pipelines, whereas models using clinical data performed robustly on all cohorts.