VLM-based Prompts as the Optimal Assistant for Unpaired Histopathology Virtual Staining

In histopathology, tissue sections are typically stained using common H&E staining or special stains (MAS, PAS, PASM, etc.) to clearly visualize specific tissue structures. The rapid advancement of deep learning offers an effective solution for generating virtually stained images, significantly reducing the time and labor costs associated with traditional histochemical staining. However, a new challenge arises in separating the fundamental visual characteristics of tissue sections from the visual differences induced by staining agents. Additionally, virtual staining often overlooks essential pathological knowledge and the physical properties of staining, resulting in only style-level transfer. To address these issues, we introduce, for the first time in virtual staining tasks, a pathological vision-language large model (VLM) as an auxiliary tool. We integrate contrastive learnable prompts, foundational concept anchors for tissue sections, and staining-specific concept anchors to leverage the extensive knowledge of the pathological VLM. This approach is designed to describe, frame, and enhance the direction of virtual staining. Furthermore, we have developed a data augmentation method based on the constraints of the VLM. This method utilizes the VLM's powerful image interpretation capabilities to further integrate image style and structural information, proving beneficial in high-precision pathological diagnostics. Extensive evaluations on publicly available multi-domain unpaired staining datasets demonstrate that our method can generate highly realistic images and enhance the accuracy of downstream tasks, such as glomerular detection and segmentation. Our code is available at: https://github.com/CZZZZZZZZZZZZZZZZZ/VPGAN-HARBOR

VGAT: A Cancer Survival Analysis Framework Transitioning from Generative Visual Question Answering to Genomic Reconstruction

Multimodal learning combining pathology images and genomic sequences enhances cancer survival analysis but faces clinical implementation barriers due to limited access to genomic sequencing in under-resourced regions. To enable survival prediction using only whole-slide images (WSI), we propose the Visual-Genomic Answering-Guided Transformer (VGAT), a framework integrating Visual Question Answering (VQA) techniques for genomic modality reconstruction. By adapting VQA's text feature extraction approach, we derive stable genomic representations that circumvent dimensionality challenges in raw genomic data. Simultaneously, a cluster-based visual prompt module selectively enhances discriminative WSI patches, addressing noise from unfiltered image regions. Evaluated across five TCGA datasets, VGAT outperforms existing WSI-only methods, demonstrating the viability of genomic-informed inference without sequencing. This approach bridges multimodal research and clinical feasibility in resource-constrained settings. The code link is https://github.com/CZZZZZZZZZZZZZZZZZ/VGAT.

Towards Unified Molecule-Enhanced Pathology Image Representation Learning via Integrating Spatial Transcriptomics

Recent advancements in multimodal pre-training models have significantly advanced computational pathology. However, current approaches predominantly rely on visual-language models, which may impose limitations from a molecular perspective and lead to performance bottlenecks. Here, we introduce a Unified Molecule-enhanced Pathology Image REpresentationn Learning framework (UMPIRE). UMPIRE aims to leverage complementary information from gene expression profiles to guide the multimodal pre-training, enhancing the molecular awareness of pathology image representation learning. We demonstrate that this molecular perspective provides a robust, task-agnostic training signal for learning pathology image embeddings. Due to the scarcity of paired data, approximately 4 million entries of spatial transcriptomics gene expression were collected to train the gene encoder. By leveraging powerful pre-trained encoders, UMPIRE aligns the encoders across over 697K pathology image-gene expression pairs. The performance of UMPIRE is demonstrated across various molecular-related downstream tasks, including gene expression prediction, spot classification, and mutation state prediction in whole slide images. Our findings highlight the effectiveness of multimodal data integration and open new avenues for exploring computational pathology enhanced by molecular perspectives. The code and pre-trained weights are available at https://github.com/Hanminghao/UMPIRE.