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Abstract This study presents CHISEL (Computer-assisted Histopathological Image Segmentation and EvaLuation), an end-to-end system capable of quantitative evaluation of benign and malignant (breast cancer) digitized tissue samples with immunohistochemical nuclear staining of various intensity and diverse compactness. It stands out with the proposed seamless segmentation based on regions of interest cropping as well as the explicit step of nuclei cluster splitting followed by a boundary refinement. The system utilizes machine learning and recursive local processing to eliminate distorted (inaccurate) outlines. The method was validated using two labeled datasets which proved the relevance of the achieved results. The evaluation was based on the IISPV dataset of tissue from biopsy of breast cancer patients, with markers of T cells, along with Warwick Beta Cell Dataset of DAB&H-stained tissue from postmortem diabetes patients. Based on the comparison of the ground truth with the results of the detected and classified objects, we conclude that the proposed method can achieve better or similar results as the state-of-the-art methods. This system deals with the complex problem of nuclei quantification in digitalized images of immunohistochemically stained tissue sections, achieving best results for DAB&H-stained breast cancer tissue samples. Our method has been prepared with user-friendly graphical interface and was optimized to fully utilize the available computing power, while being accessible to users with fewer resources than needed by deep learning techniques.

Abstract The accuracy of the applied technique for automated nuclei segmentation is critical in obtaining high-quality and efficient diagnostic results. Unfortunately, multiple objects in histopathological images are connected (clustered) and frequently counted as one. In this study, we present a new method for cluster splitting based on distance transform binarized with the recurrently increased threshold value and modified watershed algorithm. The proposed method treats clusters separately, splitting them into smaller sub-clusters and conclusively into separate objects, based solely on the shape feature, making it independent of the pixel intensity. The efficiency of these algorithms is validated based on the labeled set of images from two datasets: BBBC004v1 and breast cancer tissue microarrays. Results of initial nuclei detection were significantly improved by applying the proposed algorithms. Our approach outperformed the state-of-the-art techniques based on recall, precision, F1-score, and Jaccard index. The proposed method achieves very low amount of under-segmented, as well as over-segmented objects. In summary, we provide novel and efficient method for dividing the clustered nuclei in digital images of histopathological slides.