DUCK ‐Net: automated deep learning segmentation of ductular reactions in murine liver injury captures multicellular niche dynamics from H&E morphology

Abstract Ductular reactions (DRs) are dynamic and complex multicellular responses that occur as a result of various hepatic injuries. Precise identification and quantification of the extent of DRs is a cornerstone of pre‐clinical modelling of liver disease, with links to inflammation, fibrosis, regeneration, and disease severity. Here, we apply a deep learning model, Deep Understanding Convolutional Kernel (DUCK‐Net), to the automated detection and segmentation of DRs in whole‐slide histopathological images of murine models of liver damage. Following annotation of a training dataset by a specialist liver histopathologist, we demonstrate accelerated performance and accurate detection, achieving a mean Dice coefficient (model‐expert segmentation overlap) of 85.4% and a specificity of 98%, indicating minimal false positives. Evaluation of model validity and utility was achieved with a histological time course of cholestatic injury and recovery using 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine diet (DDC) in mice. When assessed against a multiple linear regression model incorporating core epithelial and stromal components of the DR as quantified using immunohistochemistry (IHC), DUCK‐Net predicted the spatiotemporal response to injury and repair/resolution with a coefficient of determination ( R 2 ) of 0.88. Moreover, DUCK‐Net kinetics strongly correlated with published spatial transcriptomic (Stereo‐seq) analysis of the DDC model, demonstrating that H&E‐based segmentation captured molecular DR dynamics comparable to or exceeding that of individual IHC markers without the need for immunostaining. DUCK‐Net provides a novel and accessible platform for rapid, accurate histological quantification of liver injury reflective of the matrix‐rich, multicellular regenerative niche observed in DRs. © 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.