Zero-Cost Virtual RNA: Approximating Immunotherapy Signatures via Cross-Modal WSI Retrieval

Identifying the ``Inflamed'' immunophenotype in Gastric Adenocarcinoma predicts immunotherapy response but requires an expensive 10-gene RNA signature. While deep learning on standard H\&E slides offers a scalable alternative, conventional binary classifiers oversimplify continuous RNA data and introduce label noise. To resolve this, we propose VITA (VIrtual Transcriptomic Approximation). By aligning H\&E and RNA into a joint latent space during training, VITA requires only standard H\&E at inference to retrieve morphologically similar historical cases and approximate the continuous RNA signature. Achieving 0.72 classification accuracy and a 0.66 Spearman correlation, VITA provides a cost-effective ``virtual transcriptomics'' pre-screening tool that preserves the continuous phenotypic spectrum without requiring genomic sequencing.

SCALPEL: Semantic Cross-modal Alignment via LLM-Powered Encoder Learning for Medical Vision-Language Representation

Vision-language pre-training (VLP) serves as a cornerstone for medical multimodal representation learning. However, existing medical VLP frameworks are often constrained by the limited context windows and shallow representational capacities of lightweight text encoders when processing lengthy, terminology-dense clinical reports. While integrating medical large language models (LLMs) offers unprecedented clinical reasoning capabilities, it introduces three major bottlenecks: (i) the anisotropic representational collapse of generative LLMs under standard contrastive objectives, (ii) the prohibitive memory overhead of joint end-to-end training with large batch sizes, and (iii) the medical hallucinations induced by vanilla contrastive losses that ignore fine-grained anatomical laterality and negation modifiers. To address these challenges, we propose \textbf{SCALPEL}, a \textbf{S}emantic \textbf{C}ross-modal \textbf{A}lignment framework via \textbf{L}LM-\textbf{P}owered \textbf{E}ncoder \textbf{L}earning. First, Clinical Report Contrastive fine-tuning converts a generative LLM into an isotropic encoder via domain-specific clinical text adaptation. Second, an asymmetric alignment strategy leverages offline feature caching to enable efficient training. Critically, we formulate an Anatomy-Negation Aware Objective that explicitly penalizes mismatched image-text pairs involving laterality confusion or false negations. Extensive experiments across MIMIC-CXR, CheXpert, and IU X-Ray benchmarks demonstrate that SCALPEL achieves state-of-the-art performance in cross-modal retrieval, zero-shot disease classification and medical visual question answering.