for the Alzheimer's Disease Neuroimaging Initiative
Abstract:Aligning Large Language Models (LLMs) with human preferences is often formulated via Direct Preference Optimization (DPO). However, the standard Bradley-Terry instantiation of DPO is limited in modeling common departures from transitivity in human preferences. To address this, recent work has introduced Self-Play Preference Optimization (SPPO), which iteratively refines the policy by training on self-generated win-lose pairs. Our investigation, however, reveals a critical instability in SPPO: the optimization is prone to policy degeneration when the preference oracle assigns overly confident wins to semantically indistinguishable responses. To mitigate this, we propose S-SPPO, a dual-space semantic calibration framework comprising: i) Supervision Calibration via semantic gating, which anneals win rate targets toward the maximum-entropy baseline as semantic overlap increases; and ii) Representation Calibration via latent repulsion to enforce geometric diversity to prevent manifold collapse and maintain latent diversity between chosen and rejected samples. Theoretically, we show that the calibration preserves the constant-sum game structure, facilitating convergence to a Nash Equilibrium. Empirically, S-SPPO avoids the performance degradation seen in prior methods, achieving 52.19% win rate and 47.46% length-controlled win rate on AlpacaEval 2.0 with Llama-3-8B, without using additional human-annotated preferences during training. The code will be available at https://github.com/xiwenc1/s-sppo.
Abstract:The advancement of general medical Multimodal Large Language Models (MLLMs) has shown great potential for building conversational assistants to support clinical diagnosis. However, their adaptation to highly specialized domains such as ophthalmology remains underexplored, primarily due to the scarcity of large-scale, domain-specific instruction-tuning data. Existing ophthalmic datasets for conversational agents are often limited in scale and largely rely on images from established public benchmarks, limiting the scalability of ophthalmic MLLMs and their ability to capture real-world clinical complexity. To address this gap, we propose $\textbf{OphIn-Engine}$, an ophthalmology-specific instruction data curation pipeline that constructs high-quality instruction data from open-access ophthalmology web-scale videos. The pipeline integrates multimodal transcription for extracting image-transcript pairs, visual cue separation and scoring for identifying clinically relevant visual descriptions, and instruction synthesis with quality control for generating accurate and diverse clinical dialogues. Using this engine, we introduce $\textbf{OphIn-500K}$, a large-scale multimodal ophthalmology instruction-tuning dataset containing over 500,000 instruction instances and more than 151,000 unique images from over 29,000 video clips, formatted as visual question answering (VQA), multi-turn conversational interactions, and chain-of-thought (CoT) reasoning. Built upon this dataset, we further develop $\textbf{OphIn-VL}$, an ophthalmology-specific MLLM with advanced visual understanding and conversational capabilities. Comprehensive experiments and case studies demonstrate that OphIn-VL achieves superior performance compared with state-of-the-art general medical and domain-specific MLLMs.
Abstract:Despite their popularity and success, Multimodal Large Language Models (MLLMs) often struggle to interpret images accurately, which limits their reasoning capability in complex scenarios (e.g., high object density and complex background clutter). Prior work mainly addresses this limitation by incorporating explicit visual cues like bounding boxes that require extra annotations. In addition, the resulting low-resolution crops often miss fine-grained details that MLLMs require for accurate reasoning. Therefore, we propose Mags-RL, an Agentic Reinforcement Learning (RL) framework that equips MLLMs with an external super-resolution "magnifying glass" agent for high-resolution fine-grained inspection. Specifically, the model performs two-round reasoning: in the first round, it generates an initial rationale and autonomously identifies regions of interest without relying on additional annotations; in the second round, it invokes a super-resolution agent to crop and upscale those regions, then revisits and verifies its earlier reasoning to produce the final answer. We also introduce a novel curriculum learning strategy that enables data-efficient RL training, needing as few as only 40 training samples to achieve reasonable performance. Experiments on VSR, TallyQA, and GQA subsets show its superior performance against recent strong competing methods, demonstrating high-quality reasoning with precise visual grounding. Code and weights will be released soon.
Abstract:Representation learning on large-scale unstructured volumetric and surface meshes poses significant challenges in neuroimaging, especially when models must incorporate diverse vertex-level morphometric descriptors, such as cortical thickness, curvature, sulcal depth, and myelin content, which carry subtle disease-related signals. Current approaches either ignore these clinically informative features or support only a single mesh topology, restricting their use across imaging pipelines. We introduce a hierarchical transformer framework designed for heterogeneous mesh analysis that operates on spatially adaptive tree partitions constructed from simplicial complexes of arbitrary order. This design accommodates both volumetric and surface discretizations within a single architecture, enabling efficient multi-scale attention without topology-specific modifications. A feature projection module maps variable-length per-vertex clinical descriptors into the spatial hierarchy, separating geometric structure from feature dimensionality and allowing seamless integration of different neuroimaging feature sets. Self-supervised pretraining via masked reconstruction of both coordinates and morphometric channels on large unlabeled cohorts yields a transferable encoder backbone applicable to diverse downstream tasks and mesh modalities. We validate our approach on Alzheimer's disease classification and amyloid burden prediction using volumetric brain meshes from ADNI, as well as focal cortical dysplasia detection on cortical surface meshes from the MELD dataset, achieving state-of-the-art results across all benchmarks.
Abstract:The rapid deployment of open-source frameworks has significantly advanced the development of modern multi-agent systems. However, expanded action spaces, including uncontrolled privilege exposure and hidden inter-system interactions, pose severe security challenges. Specifically, Indirect Prompt Injections (IPI), which conceal malicious instructions within third-party content, can trigger unauthorized actions such as data exfiltration during normal operations. While current security evaluations predominantly rely on isolated single-turn benchmarks, the systemic vulnerabilities of these agents within complex dynamic environments remain critically underexplored. To bridge this gap, we systematically evaluate six defense strategies against four sophisticated IPI attack vectors across nine LLM backbones. Crucially, we conduct our evaluation entirely within dynamic multi-step tool-calling environments to capture the true attack surface of modern autonomous agents. Moving beyond binary success rates, our multidimensional analysis reveals a pronounced fragility. Advanced injections successfully bypass nearly all baseline defenses, and some surface-level mitigations even produce counterproductive side effects. Furthermore, while agents execute malicious instructions almost instantaneously, their internal states exhibit abnormally high decision entropy. Motivated by this latent hesitation, we investigate Representation Engineering (RepE) as a robust detection strategy. By extracting hidden states at the tool-input position, we revealed that the RepE-based circuit breaker successfully identifies and intercepts unauthorized actions before the agent commits to them, achieving high detection accuracy across diverse LLM backbones. This study exposes the limitations of current IPI defenses and provides a highly practical paradigm for building resilient multi-agent architectures.
Abstract:Over the past decade, generative models have demonstrated success in enhancing fundus images. However, the evaluation of these models remains a challenge. A benchmark for fundus image enhancement is needed for three main reasons:(1) Conventional denoising metrics such as PSNR and SSIM fail to capture clinically relevant features, such as lesion preservation and vessel morphology consistency, limiting their applicability in real-world settings; (2) There is a lack of unified evaluation protocols that address both paired and unpaired enhancement methods, particularly those guided by clinical expertise; and (3) An evaluation framework should provide actionable insights to guide future advancements in clinically aligned enhancement models. To address these gaps, we introduce EyeBench-V2, a benchmark designed to bridge the gap between enhancement model performance and clinical utility. Our work offers three key contributions:(1) Multi-dimensional clinical-alignment through downstream evaluations: Beyond standard enhancement metrics, we assess performance across clinically meaningful tasks including vessel segmentation, diabetic retinopathy (DR) grading, generalization to unseen noise patterns, and lesion segmentation. (2) Expert-guided evaluation design: We curate a novel dataset enabling fair comparisons between paired and unpaired enhancement methods, accompanied by a structured manual assessment protocol by medical experts, which evaluates clinically critical aspects such as lesion structure alterations, background color shifts, and the introduction of artificial structures. (3) Actionable insights: Our benchmark provides a rigorous, task-oriented analysis of existing generative models, equipping clinical researchers with the evidence needed to make informed decisions, while also identifying limitations in current methods to inform the design of next-generation enhancement models.
Abstract:Black-box knowledge distillation for large language models presents a strict trade-off. Simple off-policy methods (e.g., sequence-level knowledge distillation) struggle to correct the student's inherent errors. Fully on-policy methods (e.g., Generative Adversarial Distillation) solve this via adversarial training but introduce well-known training instability and crippling computational overhead. To address this dilemma, we propose SODA (Semi On-policy Distillation with Alignment), a highly efficient alternative motivated by the inherent capability gap between frontier teachers and much smaller base models. Because a compact student model's natural, zero-shot responses are almost strictly inferior to the powerful teacher's targets, we can construct a highly effective contrastive signal simply by pairing the teacher's optimal response with a one-time static snapshot of the student's outputs. This demonstrates that exposing the small student to its own static inferior behaviors is sufficient for high-quality distribution alignment, eliminating the need for costly dynamic rollouts and fragile adversarial balancing. Extensive evaluations across four compact Qwen2.5 and Llama-3 models validate this semi on-policy paradigm. SODA matches or outperforms the state-of-the-art methods on 15 out of 16 benchmark results. More importantly, it achieves this superior distillation quality while training 10 times faster, consuming 27% less peak GPU memory, and completely eliminating adversarial instability.
Abstract:Multi-modal large language models (MLLMs) achieve strong visual-language reasoning but suffer from high inference cost due to redundant visual tokens. Recent work explores visual token pruning to accelerate inference, while existing pruning methods overlook the underlying distributional structure of visual representations. We propose OTPrune, a training-free framework that formulates pruning as distribution alignment via optimal transport (OT). By minimizing the 2-Wasserstein distance between the full and pruned token distributions, OTPrune preserves both local diversity and global representativeness while reducing inference cost. Moreover, we derive a tractable submodular objective that enables efficient optimization, and theoretically prove its monotonicity and submodularity, providing a principled foundation for stable and efficient pruning. We further provide a comprehensive analysis that explains how distributional alignment contributes to stable and semantically faithful pruning. Comprehensive experiments on wider benchmarks demonstrate that OTPrune achieves superior performance-efficiency tradeoffs compared to state-of-the-art methods. The code is available at https://github.com/xiwenc1/OTPrune.
Abstract:Retinal fundus photography is indispensable for ophthalmic screening and diagnosis, yet image quality is often degraded by noise, artifacts, and uneven illumination. Recent GAN- and diffusion-based enhancement methods improve perceptual quality by aligning degraded images with high-quality distributions, but our analysis shows that this focus can distort intra-class geometry: clinically related samples become dispersed, disease-class boundaries blur, and downstream tasks such as grading or lesion detection are harmed. The Gromov Wasserstein (GW) discrepancy offers a principled solution by aligning distributions through internal pairwise distances, naturally preserving intra-class structure, but its high computational cost restricts practical use. To overcome this, we propose SGW-GAN, the first framework to incorporate Sliced GW (SGW) into retinal image enhancement. SGW approximates GW via random projections, retaining relational fidelity while greatly reducing cost. Experiments on public datasets show that SGW-GAN produces visually compelling enhancements, achieves superior diabetic retinopathy grading, and reports the lowest GW discrepancy across disease labels, demonstrating both efficiency and clinical fidelity for unpaired medical image enhancement.
Abstract:Although Large Audio-Language Models (LALMs) deliver state-of-the-art (SOTA) performance, they frequently suffer from hallucinations, e.g. generating text not grounded in the audio input. We analyze these grounding failures and identify a distinct taxonomy: Event Omission, False Event Identity, Temporal Relation Error, and Quantitative Temporal Error. To address this, we introduce the AHA (Audio Hallucination Alignment) framework. By leveraging counterfactual hard negative mining, our pipeline constructs a high-quality preference dataset that forces models to distinguish strict acoustic evidence from linguistically plausible fabrications. Additionally, we establish AHA-Eval, a diagnostic benchmark designed to rigorously test these fine-grained temporal reasoning capabilities. We apply this data to align Qwen2.5-Omni. The resulting model, Qwen-Audio-AHA, achieves a 13.7% improvement on AHA-Eval. Crucially, this benefit generalizes beyond our diagnostic set. Our model shows substantial gains on public benchmarks, including 1.3% on MMAU-Test and 1.6% on MMAR, outperforming latest SOTA methods.