Immunohistochemical (IHC) virtual staining is a task that generates virtual IHC images from H\&E images while maintaining pathological semantic consistency with adjacent slices. This task aims to achieve cross-domain mapping between morphological structures and staining patterns through generative models, providing an efficient and cost-effective solution for pathological analysis. However, under weakly paired conditions, spatial heterogeneity between adjacent slices presents significant challenges. This can lead to inaccurate one-to-many mappings and generate results that are inconsistent with the pathological semantics of adjacent slices. To address this issue, we propose a novel unbalanced self-information feature transport for IHC virtual staining, named USIGAN, which extracts global morphological semantics without relying on positional correspondence.By removing weakly paired terms in the joint marginal distribution, we effectively mitigate the impact of weak pairing on joint distributions, thereby significantly improving the content consistency and pathological semantic consistency of the generated results. Moreover, we design the Unbalanced Optimal Transport Consistency (UOT-CTM) mechanism and the Pathology Self-Correspondence (PC-SCM) mechanism to construct correlation matrices between H\&E and generated IHC in image-level and real IHC and generated IHC image sets in intra-group level.. Experiments conducted on two publicly available datasets demonstrate that our method achieves superior performance across multiple clinically significant metrics, such as IoD and Pearson-R correlation, demonstrating better clinical relevance.
Comprehensive assessment of the various aspects of the brain's microstructure requires the use of complementary imaging techniques. This includes measuring the spatial distribution of cell bodies (cytoarchitecture) and nerve fibers (myeloarchitecture). The gold standard for cytoarchitectonic analysis is light microscopic imaging of cell-body stained tissue sections. To reveal the 3D orientations of nerve fibers, 3D Polarized Light Imaging (3D-PLI) has been introduced as a reliable technique providing a resolution in the micrometer range while allowing processing of series of complete brain sections. 3D-PLI acquisition is label-free and allows subsequent staining of sections after measurement. By post-staining for cell bodies, a direct link between fiber- and cytoarchitecture can potentially be established within the same section. However, inevitable distortions introduced during the staining process make a nonlinear and cross-modal registration necessary in order to study the detailed relationships between cells and fibers in the images. In addition, the complexity of processing histological sections for post-staining only allows for a limited number of samples. In this work, we take advantage of deep learning methods for image-to-image translation to generate a virtual staining of 3D-PLI that is spatially aligned at the cellular level. In a supervised setting, we build on a unique dataset of brain sections, to which Cresyl violet staining has been applied after 3D-PLI measurement. To ensure high correspondence between both modalities, we address the misalignment of training data using Fourier-based registration methods. In this way, registration can be efficiently calculated during training for local image patches of target and predicted staining. We demonstrate that the proposed method enables prediction of a Cresyl violet staining from 3D-PLI, matching individual cell instances.
Virtual staining leverages computer-aided techniques to transfer the style of histochemically stained tissue samples to other staining types. In virtual staining of pathological images, maintaining strict structural consistency is crucial, as these images emphasize structural integrity more than natural images. Even slight structural alterations can lead to deviations in diagnostic semantic information. Furthermore, the unpaired characteristic of virtual staining data may compromise the preservation of pathological diagnostic content. To address these challenges, we propose a dual-path inversion virtual staining method using prompt learning, which optimizes visual prompts to control content and style, while preserving complete pathological diagnostic content. Our proposed inversion technique comprises two key components: (1) Dual Path Prompted Strategy, we utilize a feature adapter function to generate reference images for inversion, providing style templates for input image inversion, called Style Target Path. We utilize the inversion of the input image as the Structural Target path, employing visual prompt images to maintain structural consistency in this path while preserving style information from the style Target path. During the deterministic sampling process, we achieve complete content-style disentanglement through a plug-and-play embedding visual prompt approach. (2) StainPrompt Optimization, where we only optimize the null visual prompt as ``operator'' for dual path inversion, rather than fine-tune pre-trained model. We optimize null visual prompt for structual and style trajectory around pivotal noise on each timestep, ensuring accurate dual-path inversion reconstruction. Extensive evaluations on publicly available multi-domain unpaired staining datasets demonstrate high structural consistency and accurate style transfer results.
Conventional hematoxylin-eosin (H&E) staining is limited to revealing cell morphology and distribution, whereas immunohistochemical (IHC) staining provides precise and specific visualization of protein activation at the molecular level. Virtual staining technology has emerged as a solution for highly efficient IHC examination, which directly transforms H&E-stained images to IHC-stained images. However, virtual staining is challenged by the insufficient mining of pathological semantics and the spatial misalignment of pathological semantics. To address these issues, we propose the Pathological Semantics-Preserving Learning method for Virtual Staining (PSPStain), which directly incorporates the molecular-level semantic information and enhances semantics interaction despite any spatial inconsistency. Specifically, PSPStain comprises two novel learning strategies: 1) Protein-Aware Learning Strategy (PALS) with Focal Optical Density (FOD) map maintains the coherence of protein expression level, which represents molecular-level semantic information; 2) Prototype-Consistent Learning Strategy (PCLS), which enhances cross-image semantic interaction by prototypical consistency learning. We evaluate PSPStain on two public datasets using five metrics: three clinically relevant metrics and two for image quality. Extensive experiments indicate that PSPStain outperforms current state-of-the-art H&E-to-IHC virtual staining methods and demonstrates a high pathological correlation between the staging of real and virtual stains.
The presence and density of specific types of immune cells are important to understand a patient's immune response to cancer. However, immunofluorescence staining required to identify T cell subtypes is expensive, time-consuming, and rarely performed in clinical settings. We present a framework to virtually stain Hoechst images (which are cheap and widespread) with both CD3 and CD8 to identify T cell subtypes in clear cell renal cell carcinoma using generative adversarial networks. Our proposed method jointly learns both staining tasks, incentivising the network to incorporate mutually beneficial information from each task. We devise a novel metric to quantify the virtual staining quality, and use it to evaluate our method.