A3-TTA: Adaptive Anchor Alignment Test-Time Adaptation for Image Segmentation

Test-Time Adaptation (TTA) offers a practical solution for deploying image segmentation models under domain shift without accessing source data or retraining. Among existing TTA strategies, pseudo-label-based methods have shown promising performance. However, they often rely on perturbation-ensemble heuristics (e.g., dropout sampling, test-time augmentation, Gaussian noise), which lack distributional grounding and yield unstable training signals. This can trigger error accumulation and catastrophic forgetting during adaptation. To address this, we propose \textbf{A3-TTA}, a TTA framework that constructs reliable pseudo-labels through anchor-guided supervision. Specifically, we identify well-predicted target domain images using a class compact density metric, under the assumption that confident predictions imply distributional proximity to the source domain. These anchors serve as stable references to guide pseudo-label generation, which is further regularized via semantic consistency and boundary-aware entropy minimization. Additionally, we introduce a self-adaptive exponential moving average strategy to mitigate label noise and stabilize model update during adaptation. Evaluated on both multi-domain medical images (heart structure and prostate segmentation) and natural images, A3-TTA significantly improves average Dice scores by 10.40 to 17.68 percentage points compared to the source model, outperforming several state-of-the-art TTA methods under different segmentation model architectures. A3-TTA also excels in continual TTA, maintaining high performance across sequential target domains with strong anti-forgetting ability. The code will be made publicly available at https://github.com/HiLab-git/A3-TTA.

SRA-Seg: Synthetic to Real Alignment for Semi-Supervised Medical Image Segmentation

Synthetic data, an appealing alternative to extensive expert-annotated data for medical image segmentation, consistently fails to improve segmentation performance despite its visual realism. The reason being that synthetic and real medical images exist in different semantic feature spaces, creating a domain gap that current semi-supervised learning methods cannot bridge. We propose SRA-Seg, a framework explicitly designed to align synthetic and real feature distributions for medical image segmentation. SRA-Seg introduces a similarity-alignment (SA) loss using frozen DINOv2 embeddings to pull synthetic representations toward their nearest real counterparts in semantic space. We employ soft edge blending to create smooth anatomical transitions and continuous labels, eliminating the hard boundaries from traditional copy-paste augmentation. The framework generates pseudo-labels for synthetic images via an EMA teacher model and applies soft-segmentation losses that respect uncertainty in mixed regions. Our experiments demonstrate strong results: using only 10% labeled real data and 90% synthetic unlabeled data, SRA-Seg achieves 89.34% Dice on ACDC and 84.42% on FIVES, significantly outperforming existing semi-supervised methods and matching the performance of methods using real unlabeled data.

MedSAM-Agent: Empowering Interactive Medical Image Segmentation with Multi-turn Agentic Reinforcement Learning

Medical image segmentation is evolving from task-specific models toward generalizable frameworks. Recent research leverages Multi-modal Large Language Models (MLLMs) as autonomous agents, employing reinforcement learning with verifiable reward (RLVR) to orchestrate specialized tools like the Segment Anything Model (SAM). However, these approaches often rely on single-turn, rigid interaction strategies and lack process-level supervision during training, which hinders their ability to fully exploit the dynamic potential of interactive tools and leads to redundant actions. To bridge this gap, we propose MedSAM-Agent, a framework that reformulates interactive segmentation as a multi-step autonomous decision-making process. First, we introduce a hybrid prompting strategy for expert-curated trajectory generation, enabling the model to internalize human-like decision heuristics and adaptive refinement strategies. Furthermore, we develop a two-stage training pipeline that integrates multi-turn, end-to-end outcome verification with a clinical-fidelity process reward design to promote interaction parsimony and decision efficiency. Extensive experiments across 6 medical modalities and 21 datasets demonstrate that MedSAM-Agent achieves state-of-the-art performance, effectively unifying autonomous medical reasoning with robust, iterative optimization. Code is available \href{https://github.com/CUHK-AIM-Group/MedSAM-Agent}{here}.

Bayesian Integration of Nonlinear Incomplete Clinical Data

Multimodal clinical data are characterized by high dimensionality, heterogeneous representations, and structured missingness, posing significant challenges for predictive modeling, data integration, and interpretability. We propose BIONIC (Bayesian Integration of Nonlinear Incomplete Clinical data), a unified probabilistic framework that integrates heterogeneous multimodal data under missingness through a joint generative-discriminative latent architecture. BIONIC uses pretrained embeddings for complex modalities such as medical images and clinical text, while incorporating structured clinical variables directly within a Bayesian multimodal formulation. The proposed framework enables robust learning in partially observed and semi-supervised settings by explicitly modeling modality-level and variable-level missingness, as well as missing labels. We evaluate BIONIC on three multimodal clinical and biomedical datasets, demonstrating strong and consistent discriminative performance compared to representative multimodal baselines, particularly under incomplete data scenarios. Beyond predictive accuracy, BIONIC provides intrinsic interpretability through its latent structure, enabling population-level analysis of modality relevance and supporting clinically meaningful insight.

Scale-Cascaded Diffusion Models for Super-Resolution in Medical Imaging

Diffusion models have been increasingly used as strong generative priors for solving inverse problems such as super-resolution in medical imaging. However, these approaches typically utilize a diffusion prior trained at a single scale, ignoring the hierarchical scale structure of image data. In this work, we propose to decompose images into Laplacian pyramid scales and train separate diffusion priors for each frequency band. We then develop an algorithm to perform super-resolution that utilizes these priors to progressively refine reconstructions across different scales. Evaluated on brain, knee, and prostate MRI data, our approach both improves perceptual quality over baselines and reduces inference time through smaller coarse-scale networks. Our framework unifies multiscale reconstruction and diffusion priors for medical image super-resolution.

Investigation into using stochastic embedding representations for evaluating the trustworthiness of the Fréchet Inception Distance

Feature embeddings acquired from pretrained models are widely used in medical applications of deep learning to assess the characteristics of datasets; e.g. to determine the quality of synthetic, generated medical images. The Fréchet Inception Distance (FID) is one popular synthetic image quality metric that relies on the assumption that the characteristic features of the data can be detected and encoded by an InceptionV3 model pretrained on ImageNet1K (natural images). While it is widely known that this makes it less effective for applications involving medical images, the extent to which the metric fails to capture meaningful differences in image characteristics is not obviously known. Here, we use Monte Carlo dropout to compute the predictive variance in the FID as well as a supplemental estimate of the predictive variance in the feature embedding model's latent representations. We show that the magnitudes of the predictive variances considered exhibit varying degrees of correlation with the extent to which test inputs (ImageNet1K validation set augmented at various strengths, and other external datasets) are out-of-distribution relative to its training data, providing some insight into the effectiveness of their use as indicators of the trustworthiness of the FID.

MedAD-R1: Eliciting Consistent Reasoning in Interpretible Medical Anomaly Detection via Consistency-Reinforced Policy Optimization

Medical Anomaly Detection (MedAD) presents a significant opportunity to enhance diagnostic accuracy using Large Multimodal Models (LMMs) to interpret and answer questions based on medical images. However, the reliance on Supervised Fine-Tuning (SFT) on simplistic and fragmented datasets has hindered the development of models capable of plausible reasoning and robust multimodal generalization. To overcome this, we introduce MedAD-38K, the first large-scale, multi-modal, and multi-center benchmark for MedAD featuring diagnostic Chain-of-Thought (CoT) annotations alongside structured Visual Question-Answering (VQA) pairs. On this foundation, we propose a two-stage training framework. The first stage, Cognitive Injection, uses SFT to instill foundational medical knowledge and align the model with a structured think-then-answer paradigm. Given that standard policy optimization can produce reasoning that is disconnected from the final answer, the second stage incorporates Consistency Group Relative Policy Optimization (Con-GRPO). This novel algorithm incorporates a crucial consistency reward to ensure the generated reasoning process is relevant and logically coherent with the final diagnosis. Our proposed model, MedAD-R1, achieves state-of-the-art (SOTA) performance on the MedAD-38K benchmark, outperforming strong baselines by more than 10\%. This superior performance stems from its ability to generate transparent and logically consistent reasoning pathways, offering a promising approach to enhancing the trustworthiness and interpretability of AI for clinical decision support.

Region-Normalized DPO for Medical Image Segmentation under Noisy Judges

While dense pixel-wise annotations remain the gold standard for medical image segmentation, they are costly to obtain and limit scalability. In contrast, many deployed systems already produce inexpensive automatic quality-control (QC) signals like model agreement, uncertainty measures, or learned mask-quality scores which can be used for further model training without additional ground-truth annotation. However, these signals can be noisy and biased, making preference-based fine-tuning susceptible to harmful updates. We study Direct Preference Optimization (DPO) for segmentation from such noisy judges using proposals generated by a supervised base segmenter trained on a small labeled set. We find that outcomes depend strongly on how preference pairs are mined: selecting the judge's top-ranked proposal can improve peak performance when the judge is reliable, but can amplify harmful errors under weaker judges. We propose Region-Normalized DPO (RN-DPO), a segmentation-aware objective which normalizes preference updates by the size of the disagreement region between masks, reducing the leverage of harmful comparisons and improving optimization stability. Across two medical datasets and multiple regimes, RN-DPO improves sustained performance and stabilizes preference-based fine-tuning, outperforming standard DPO and strong baselines without requiring additional pixel annotations.

PathReasoner-R1: Instilling Structured Reasoning into Pathology Vision-Language Model via Knowledge-Guided Policy Optimization

Vision-Language Models (VLMs) are advancing computational pathology with superior visual understanding capabilities. However, current systems often reduce diagnosis to directly output conclusions without verifiable evidence-linked reasoning, which severely limits clinical trust and hinders expert error rectification. To address these barriers, we construct PathReasoner, the first large-scale dataset of whole-slide image (WSI) reasoning. Unlike previous work reliant on unverified distillation, we develop a rigorous knowledge-guided generation pipeline. By leveraging medical knowledge graphs, we explicitly align structured pathological findings and clinical reasoning with diagnoses, generating over 20K high-quality instructional samples. Based on the database, we propose PathReasoner-R1, which synergizes trajectory-masked supervised fine-tuning with reasoning-oriented reinforcement learning to instill structured chain-of-thought capabilities. To ensure medical rigor, we engineer a knowledge-aware multi-granular reward function incorporating an Entity Reward mechanism strictly aligned with knowledge graphs. This effectively guides the model to optimize for logical consistency rather than mere outcome matching, thereby enhancing robustness. Extensive experiments demonstrate that PathReasoner-R1 achieves state-of-the-art performance on both PathReasoner and public benchmarks across various image scales, equipping pathology models with transparent, clinically grounded reasoning capabilities. Dataset and code are available at https://github.com/cyclexfy/PathReasoner-R1.

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.