PathAR: Structure-First Autoregressive Synthesis of Multimodal Pathology Images

Data scarcity in multimodal pathology motivates unified generative models that synthesize modality-specific appearance while preserving anatomically coherent structure. Although modalities differ in appearance statistics, morphological structures such as cellular topology and tissue boundaries are largely preserved across acquisition protocols. However, existing methods often model these factors within a homogeneous token stream, implicitly coupling structure with appearance and weakening structural controllability under modality shifts. To address this, we propose pathology Autorgressive modeling (PathAR), a structure-first autoregressive synthesis framework that explicitly factorizes structure and appearance for modality-label-conditioned pathology generation.PathAR employs a dual vector quantization (Dual-VQ) tokenizer to decompose samples into mask-grounded structure and appearance tokens, and an interleaved autoregressive (IAR) transformer with asymmetric attention visibility to enforce structure-to-appearance dependence. PathAR stabilizes morphology under heterogeneous modality-specific appearances and enables spatially aligned image--mask pair generation. Extensive experiments show that PathAR improves structural consistency and modality fidelity over baselines, maintains sample diversity, supports downstream segmentation in data-scarce regimes, and demonstrates extensibility to finer-grained intra-modality organ-label variation.

MARVEL: Universal Murray's Law-informed Vessel Tree Segmentation and Topology Estimation

Vascular circulation follows fundamental biophysical principles that optimize mass transport and metabolic energy expenditure, which can be effectively modeled by Murray's law. However, contemporary deep learning methods for vascular segmentation often neglect these biophysical constraints. This leads to physiologically implausible branching and misclassification vascular trees, rendering. These automated segmentation results are unreliable unreliable for downstream clinical tasks such as blood flow simulation or disease quantification. In this paper, we introduce MARVEL (Universal MurrAy's law-infoRmed Vessel sEgmentation and topoLogy estimation), a backbone-agnostic framework that integrates biophysical priors into vascular tree extraction. MARVEL combines per-pixel supervision with explicit radius predictions to enforce local bifurcation constraints derived from an empirical width-exponent mapping. We implement these constraints as differentiable regularizers during training to guide models toward physiologically consistent reconstructions. We evaluate MARVEL on eight public datasets across multiple vascular modalities and segmentation backbones. Results demonstrate MARVEL's superior performance in segmentation accuracy, topological consistency, and physiological plausibility. By converting segmented masks into graph-based hemodynamic simulations, we demonstrate that MARVEL preserves the subtle pathological narrowing and topological connectivity required to distinguish hypertensive from normotensive eyes. Results show that MARVEL significantly improves the classification of hypertension via arteriovenous pressure differences in the eye (p < 0.001), outperforming baseline models in both topological consistency and clinical predictive value.

Towards Clinically Interpretable Ophthalmic VQA via Spatially-Grounded Lesion Evidence

Visual Question Answering (VQA) holds great promise for clinical support, particularly in ophthalmology, where retinal fundus photography is essential for diagnosis. However, ophthalmic VQA benchmarks primarily emphasize answer accuracy, neglecting the explicit visual evidence necessary for clinical interpretability. In this work, we introduce FundusGround, a new benchmark for clinically interpretable ophthalmic VQA with spatially-grounded lesion evidence. Specifically, we propose a three-stage pipeline that collects 10,719 fundus images with 15,595 image-level meticulously annotated lesions. To ensure anatomical consistency and clinical validity, all lesions are spatially localized using the Early Treatment Diabetic Retinopathy Study (ETDRS) grid, enabling standardized mapping to nine clinically meaningful retinal regions. Built upon this structured lesion evidence, 72,706 questions are then generated spanning four formats: open-ended, closed-ended, single-choice, and multiple-choice. We further benchmark multiple general- and medical- large vision-language models using dual metrics for answer accuracy and lesion-level reasoning. The experiments demonstrate that incorporating lesion-level visual evidence consistently improves model performance and transparency, highlighting the necessity of explicit spatial grounding for reliable and explainable ophthalmic VQA.

Thinking in Scales: Accelerating Gigapixel Pathology Image Analysis via Adaptive Continuous Reasoning

Traditional whole slide image (WSI) analysis methods typically rely on the multiple instance learning (MIL) paradigm, which extracts patch-level features at high magnification and aggregates them for slide-level prediction. However, such exhaustive patch-level processing is computationally expensive, severely limiting the efficiency and scalability of WSI analysis. To address this challenge, we propose PathCTM (a Pathology-oriented Continuous Thought Model) that enables token-efficient scale-space continuous reasoning for gigapixel WSIs. PathCTM formulates diagnostic inference as a dynamic sequential information pursuit. It progressively transitions from low-magnification global to high-magnification local inspection, and adaptively terminates inference when sufficient evidence is gathered to effectively bound decision uncertainty. Specifically, it uses conditional computation for dynamic scale switching with attention-guided region pruning, coupled with confidence-aware early stopping. Extensive experiments demonstrate that, compared with standard MIL-based methods, PathCTM reduces the number of required image patches by 95.95% and shortens inference time by approximately 95.62%, while maintaining AUC without degradation. Code is available at https://github.com/JSGe-AI/PathCTM.

PRIME: Prototype-Driven Multimodal Pretraining for Cancer Prognosis with Missing Modalities

Multimodal self-supervised pretraining offers a promising route to cancer prognosis by integrating histopathology whole-slide images, gene expression, and pathology reports, yet most existing approaches require fully paired and complete inputs. In practice, clinical cohorts are fragmented and often miss one or more modalities, limiting both supervised fusion and scalable multimodal pretraining. We propose PRIME, a missing-aware multimodal self-supervised pretraining framework that learns robust and transferable representations from partially observed cohorts. PRIME maps heterogeneous modality embeddings into a unified token space and introduces a shared prototype memory bank for latent-space semantic imputation via patient-level consensus retrieval, producing structurally aligned tokens without reconstructing raw signals. Two complementary pretraining objectives: inter-modality alignment and post-fusion consistency under structured missingness augmentation, jointly learn representations that remain predictive under arbitrary modality subsets. We evaluate PRIME on The Cancer Genome Atlas with label-free pretraining on 32 cancer types and downstream 5-fold evaluation on five cohorts across overall survival prediction, 3-year mortality classification, and 3-year recurrence classification. PRIME achieves the best macro-average performance among all compared methods, reaching 0.653 C-index, 0.689 AUROC, and 0.637 AUROC on the three tasks, respectively, while improving robustness under test-time missingness and supporting parameter-efficient and label-efficient adaptation. These results support missing-aware multimodal pretraining as a practical strategy for prognosis modeling in fragmented clinical data settings.

Enhancing Medical Visual Grounding via Knowledge-guided Spatial Prompts

Medical Visual Grounding (MVG) aims to identify diagnostically relevant phrases from free-text radiology reports and localize their corresponding regions in medical images, providing interpretable visual evidence to support clinical decision-making. Although recent Vision-Language Models (VLMs) exhibit promising multimodal reasoning ability, their grounding remains insufficient spatial precision, largely due to a lack of explicit localization priors when relying solely on latent embeddings. In this work, we analyze this limitation from an attention perspective and propose KnowMVG, a Knowledge-prior and global-local attention enhancement framework for MVG in VLMs that explicitly strengthens spatial awareness during decoding. Specifically, we present a knowledge-enhanced prompting strategy that encodes phrase related medical knowledge into compact embeddings, together with a global-local attention that jointly leverages coarse global information and refined local cues to guide precise region localization. localization. This design bridges high-level semantic understanding and fine-grained visual perception without introducing extra textual reasoning overhead. Extensive experiments on four MVG benchmarks demonstrate that our KnowMVG consistently outperforms existing approaches, achieving gains of 3.0% in AP50 and 2.6% in mIoU over prior state-of-the-art methods. Qualitative and ablation studies further validate the effectiveness of each component.

Authorize-on-Demand: Dynamic Authorization with Legality-Aware Intellectual Property Protection for VLMs

The rapid adoption of vision-language models (VLMs) has heightened the demand for robust intellectual property (IP) protection of these high-value pretrained models. Effective IP protection should proactively confine model deployment within authorized domains and prevent unauthorized transfers. However, existing methods rely on static training-time definitions, limiting flexibility in dynamic environments and often producing opaque responses to unauthorized inputs. To address these limitations, we propose a novel dynamic authorization with legality-aware intellectual property protection (AoD-IP) for VLMs, a framework that supports authorize-on-demand and legality-aware assessment. AoD-IP introduces a lightweight dynamic authorization module that enables flexible, user-controlled authorization, allowing users to actively specify or switch authorized domains on demand at deployment time. This enables the model to adapt seamlessly as application scenarios evolve and provides substantially greater extensibility than existing static-domain approaches. In addition, AoD-IP incorporates a dual-path inference mechanism that jointly predicts input legality-aware and task-specific outputs. Comprehensive experimental results on multiple cross-domain benchmarks demonstrate that AoD-IP maintains strong authorized-domain performance and reliable unauthorized detection, while supporting user-controlled authorization for adaptive deployment in dynamic environments.

Structure-constrained Language-informed Diffusion Model for Unpaired Low-dose Computed Tomography Angiography Reconstruction

The application of iodinated contrast media (ICM) improves the sensitivity and specificity of computed tomography (CT) for a wide range of clinical indications. However, overdose of ICM can cause problems such as kidney damage and life-threatening allergic reactions. Deep learning methods can generate CT images of normal-dose ICM from low-dose ICM, reducing the required dose while maintaining diagnostic power. However, existing methods are difficult to realize accurate enhancement with incompletely paired images, mainly because of the limited ability of the model to recognize specific structures. To overcome this limitation, we propose a Structure-constrained Language-informed Diffusion Model (SLDM), a unified medical generation model that integrates structural synergy and spatial intelligence. First, the structural prior information of the image is effectively extracted to constrain the model inference process, thus ensuring structural consistency in the enhancement process. Subsequently, semantic supervision strategy with spatial intelligence is introduced, which integrates the functions of visual perception and spatial reasoning, thus prompting the model to achieve accurate enhancement. Finally, the subtraction angiography enhancement module is applied, which serves to improve the contrast of the ICM agent region to suitable interval for observation. Qualitative analysis of visual comparison and quantitative results of several metrics demonstrate the effectiveness of our method in angiographic reconstruction for low-dose contrast medium CT angiography.

Topology-aware Pathological Consistency Matching for Weakly-Paired IHC Virtual Staining

Immunohistochemical (IHC) staining provides crucial molecular characterization of tissue samples and plays an indispensable role in the clinical examination and diagnosis of cancers. However, compared with the commonly used Hematoxylin and Eosin (H&E) staining, IHC staining involves complex procedures and is both time-consuming and expensive, which limits its widespread clinical use. Virtual staining converts H&E images to IHC images, offering a cost-effective alternative to clinical IHC staining. Nevertheless, using adjacent slides as ground truth often results in weakly-paired data with spatial misalignment and local deformations, hindering effective supervised learning. To address these challenges, we propose a novel topology-aware framework for H&E-to-IHC virtual staining. Specifically, we introduce a Topology-aware Consistency Matching (TACM) mechanism that employs graph contrastive learning and topological perturbations to learn robust matching patterns despite spatial misalignments, ensuring structural consistency. Furthermore, we propose a Topology-constrained Pathological Matching (TCPM) mechanism that aligns pathological positive regions based on node importance to enhance pathological consistency. Extensive experiments on two benchmarks across four staining tasks demonstrate that our method outperforms state-of-the-art approaches, achieving superior generation quality with higher clinical relevance.

Plasticine: A Traceable Diffusion Model for Medical Image Translation

Domain gaps arising from variations in imaging devices and population distributions pose significant challenges for machine learning in medical image analysis. Existing image-to-image translation methods primarily aim to learn mappings between domains, often generating diverse synthetic data with variations in anatomical scale and shape, but they usually overlook spatial correspondence during the translation process. For clinical applications, traceability, defined as the ability to provide pixel-level correspondences between original and translated images, is equally important. This property enhances clinical interpretability but has been largely overlooked in previous approaches. To address this gap, we propose Plasticine, which is, to the best of our knowledge, the first end-to-end image-to-image translation framework explicitly designed with traceability as a core objective. Our method combines intensity translation and spatial transformation within a denoising diffusion framework. This design enables the generation of synthetic images with interpretable intensity transitions and spatially coherent deformations, supporting pixel-wise traceability throughout the translation process.