Cyto R-CNN and CytoNuke Dataset: Towards reliable whole-cell segmentation in bright-field histological images

Background: Cell segmentation in bright-field histological slides is a crucial topic in medical image analysis. Having access to accurate segmentation allows researchers to examine the relationship between cellular morphology and clinical observations. Unfortunately, most segmentation methods known today are limited to nuclei and cannot segmentate the cytoplasm. Material & Methods: We present a new network architecture Cyto R-CNN that is able to accurately segment whole cells (with both the nucleus and the cytoplasm) in bright-field images. We also present a new dataset CytoNuke, consisting of multiple thousand manual annotations of head and neck squamous cell carcinoma cells. Utilizing this dataset, we compared the performance of Cyto R-CNN to other popular cell segmentation algorithms, including QuPath's built-in algorithm, StarDist and Cellpose. To evaluate segmentation performance, we calculated AP50, AP75 and measured 17 morphological and staining-related features for all detected cells. We compared these measurements to the gold standard of manual segmentation using the Kolmogorov-Smirnov test. Results: Cyto R-CNN achieved an AP50 of 58.65% and an AP75 of 11.56% in whole-cell segmentation, outperforming all other methods (QuPath $19.46/0.91\%$; StarDist $45.33/2.32\%$; Cellpose $31.85/5.61\%$). Cell features derived from Cyto R-CNN showed the best agreement to the gold standard ($\bar{D} = 0.15$) outperforming QuPath ($\bar{D} = 0.22$), StarDist ($\bar{D} = 0.25$) and Cellpose ($\bar{D} = 0.23$). Conclusion: Our newly proposed Cyto R-CNN architecture outperforms current algorithms in whole-cell segmentation while providing more reliable cell measurements than any other model. This could improve digital pathology workflows, potentially leading to improved diagnosis. Moreover, our published dataset can be used to develop further models in the future.