When Does Synthetic CT Transfer? A Label-Free Donor/Host Diagnostic for Medical Vision-Language Model Routing on Real Lung CT

3D CT vision-language models (VLMs) classify abnormalities from text prompts in a zero-shot manner, enabling cross-institution deployment where labels are scarce and clinical tasks shift faster than supervised models can be retrained. A real CT scan, however, typically contains several co-occurring abnormalities, and the reliability of zero-shot multi-label prediction under distribution shift remains poorly understood. Test-time adaptation (TTA) updates a model on unlabeled target scans without source data or target annotations, yet existing TTA methods target multi-class softmax prediction on natural images or 2D medical segmentation, and none addresses unsupervised multi-label adaptation for zero-shot 3D CT VLMs. We study when TTA helps zero-shot 3D CT VLMs. A controlled diagnostic analysis shows that TTA is conditional: the volumetric input must preserve the encoder's depth structure, and the base representation must transfer to the target cohort, with depth reduction alone lowering internal AUROC by more than 0.12. We then focus on the regime where the base model already separates present from absent abnormalities. We introduce CARVE (Cardinality-Aware Retained-View Entropy), the first TTA method for this setting. CARVE estimates a sample-specific positive-label cardinality $\hat{k}$, optimizes a top-$\hat{k}$ objective to preserve co-occurring abnormalities, and performs memory-efficient multi-view adaptation by scoring weak 3D views without gradients before updating on a retained subset. Across contrastive CT-CLIP and anatomy-aware fVLM, CARVE provides the most consistent improvements across multi-label, three-class, and binary CT tasks when the base model is already discriminative. These results establish multi-label TTA for zero-shot 3D CT VLMs as a distinct problem and CARVE as a cardinality-aware solution.

We introduce iTRIALSPACE, a programmable evaluation framework for controlled assessment of lung CT models. Standard benchmarks are static retrospective collections that entangle lesion size, lobe prevalence, anatomy, and acquisition context, making it difficult to determine what structurally drives model accuracy. iTRIALSPACE addresses this limitation by composing real clinical CTs and lesion profiles into controlled virtual lesion trials through a four-stage pipeline: multidataset nodule profiling, explicit trial specification, anatomy-aware mask insertion, and ControlNet-conditioned CT synthesis. The framework is built on a unified 54-attribute nodule-profile dataset spanning 13,140 annotated nodules from seven public CT sources and instantiated as 13 trial modes. We evaluate iTRIALSPACE in a 55,469-sample Virtual Lesion Study spanning three medical VLMs, four spatialguidance conditions, and three clinical tasks. Across all 13 modes, the synthetic substrate remains within the real-to-real FID baseline, and synthetic performance rankings transfer strongly to real clinical data ($ρ$ = 0.93, p < 10$^{-15}$). Controlled trial modes expose findings unavailable to fixed-distribution benchmarks, including shortcut-driven size prediction collapse under lobe-equalized sampling and hostto-donor variance ratios of 8.9x and 3.3x in twin-cross analysis. These results position iTRIALSPACE as an auditable evaluation infrastructure for controlled, falsifiable testing beyond static retrospective benchmarks.

Vision-language pre-training (VLP) holds great promise for general-purpose medical AI by leveraging radiology reports as rich textual supervision, yet existing methods struggle with 3D CT imaging due to inefficient visual backbones and coarse semantic alignment. To address these issues, we propose a tailored VLP framework featuring three key components: (1) a CNN-ViT hybrid encoder that replaces ViT's patch embedding with a 3D CNN backbone to efficiently capture local anatomical details while preserving global attention and compatibility with pre-trained cross-modal priors; (2) a disease-level contrastive learning mechanism using learnable query tokens to dynamically extract disease-specific semantics from full reports and align them with corresponding visual features, thereby disentangling distinct diseases within the same anatomical region; and (3) a diagnosis-aware prompt strategy that employs real clinical phrases and aggregated disease prototypes to bridge the pre-training-inference gap and enhance zero-shot diagnostic reliability. Our model achieves state-of-the-art performance on CT-RATE (84.4% AUC, +5.1%) and Rad-ChestCT (75.4% AUC, +5.4%), with even larger gains (+9.8% AUC) on a challenging 60-disease benchmark, and demonstrates strong transferability to radiology report generation, underscoring the generality and clinical utility of our approach.