Blind stain separation using model-aware generative learning and its applications on fluorescence microscopy images

Abstract

Multiple stains are usually used to highlight biological substances in biomedical image analysis. To decompose multiple stains for co-localization quantification, blind source separation is usually performed. Prior model-based stain separation methods usually rely on stains’ spatial distributions over an image and may fail to solve the co-localization problem. With the advantage of machine learning, deep generative models are used for this purpose. Since prior knowledge of imaging models is ignored in purely data-driven solutions, these methods may be suboptimal. In this study, a novel learning-based blind source separation framework is proposed, where the physical model of biomedical imaging is incorporated to regularize the learning process. The introduced modelrelevant adversarial loss couples all generators in the framework and limits the capacities of the generative models. Further more, a training algorithm is innovated for the proposed framework to avoid inter-generator confusion during learning. This paper particularly takes fluorescence unmixing in fluorescence microscopy images as an application example of the proposed framework. Qualitative and quantitative experimentation on a public fluorescence microscopy image set demonstrates the superiority of the proposed method over both prior model-based approaches and learning-based methods.