Nuclear Segmentation in Histopathological Images Using Two-Stage Stacked U-Nets With Attention Mechanism

Nuclei segmentation is a fundamental but challenging task in histopathological image analysis. One of the main problems is the existence of overlapping regions which increases the difficulty of independent nuclei separation. In this study, to solve the segmentation of nuclei and overlapping regions, we introduce a nuclei segmentation method based on two-stage learning framework consisting of two connected Stacked U-Nets (SUNets). The proposed SUNets consists of four parallel backbone nets, which are merged by the attention generation model. In the first stage, a Stacked U-Net is utilized to predict pixel-wise segmentation of nuclei. The output binary map together with RGB values of the original images are concatenated as the input of the second stage of SUNets. Due to the sizable imbalance of overlapping and background regions, the first network is trained with cross-entropy loss, while the second network is trained with focal loss. We applied the method on two publicly available datasets and achieved state-of-the-art performance for nuclei segmentation–mean Aggregated Jaccard Index (AJI) results were 0.5965 and 0.6210, and F1 scores were 0.8247 and 0.8060, respectively; our method also segmented the overlapping regions between nuclei, with average AJI = 0.3254. The proposed two-stage learning framework outperforms many current segmentation methods, and the consistent good segmentation performance on images from different organs indicates the generalized adaptability of our approach.