PST-Diff: Achieving High-consistency Stain Transfer by Diffusion Models with Pathological and Structural Constraints.

Histopathological examinations heavily rely on hematoxylin and eosin (HE) and immunohistochemistry (IHC) staining. IHC staining can offer more accurate diagnostic details but it brings significant financial and time costs. Furthermore, either re-staining HE-stained slides or using adjacent slides for IHC may compromise the accuracy of pathological diagnosis due to information loss. To address these challenges, we develop PST-Diff, a method for generating virtual IHC images from HE images based on diffusion models, which allows pathologists to simultaneously view multiple staining results from the same tissue slide. To maintain the pathological consistency of the stain transfer, we propose the asymmetric attention mechanism (AAM) and latent transfer (LT) module in PST-Diff. Specifically, the AAM can retain more local pathological information of the source domain images through the design of asymmetric attention mechanisms, while ensuring the model's flexibility in generating virtual stained images that highly confirm to the target domain. Subsequently, the LT module transfers the implicit representations across different domains, effectively alleviating the bias introduced by direct connection and further enhancing the pathological consistency of PST-Diff. Furthermore, to maintain the structural consistency of the stain transfer, the conditional frequency guidance (CFG) module is proposed to precisely control image generation and preserve structural details according to the frequency recovery process. To conclude, the pathological and structural consistency constraints provide PST-Diff with effectiveness and superior generalization in generating stable and functionally pathological IHC images with the best evaluation score. In general, PST-Diff offers prospective application in clinical virtual staining and pathological image analysis.