Quasi-multimodal-based pathophysiological feature learning for retinal disease diagnosis

Retinal diseases spanning a broad spectrum can be effectively identified and diagnosed using complementary signals from multimodal data. However, multimodal diagnosis in ophthalmic practice is typically challenged in terms of data heterogeneity, potential invasiveness, registration complexity, and so on. As such, a unified framework that integrates multimodal data synthesis and fusion is proposed for retinal disease classification and grading. Specifically, the synthesized multimodal data incorporates fundus fluorescein angiography (FFA), multispectral imaging (MSI), and saliency maps that emphasize latent lesions as well as optic disc/cup regions. Parallel models are independently trained to learn modality-specific representations that capture cross-pathophysiological signatures. These features are then adaptively calibrated within and across modalities to perform information pruning and flexible integration according to downstream tasks. The proposed learning system is thoroughly interpreted through visualizations in both image and feature spaces. Extensive experiments on two public datasets demonstrated the superiority of our approach over state-of-the-art ones in the tasks of multi-label classification (F1-score: 0.683, AUC: 0.953) and diabetic retinopathy grading (Accuracy:0.842, Kappa: 0.861). This work not only enhances the accuracy and efficiency of retinal disease screening but also offers a scalable framework for data augmentation across various medical imaging modalities.

Inference-Time Dynamic Modality Selection for Incomplete Multimodal Classification

Multimodal deep learning (MDL) has achieved remarkable success across various domains, yet its practical deployment is often hindered by incomplete multimodal data. Existing incomplete MDL methods either discard missing modalities, risking the loss of valuable task-relevant information, or recover them, potentially introducing irrelevant noise, leading to the discarding-imputation dilemma. To address this dilemma, in this paper, we propose DyMo, a new inference-time dynamic modality selection framework that adaptively identifies and integrates reliable recovered modalities, fully exploring task-relevant information beyond the conventional discard-or-impute paradigm. Central to DyMo is a novel selection algorithm that maximizes multimodal task-relevant information for each test sample. Since direct estimation of such information at test time is intractable due to the unknown data distribution, we theoretically establish a connection between information and the task loss, which we compute at inference time as a tractable proxy. Building on this, a novel principled reward function is proposed to guide modality selection. In addition, we design a flexible multimodal network architecture compatible with arbitrary modality combinations, alongside a tailored training strategy for robust representation learning. Extensive experiments on diverse natural and medical image datasets show that DyMo significantly outperforms state-of-the-art incomplete/dynamic MDL methods across various missing-data scenarios. Our code is available at https://github.com//siyi-wind/DyMo.

LLM is Not All You Need: A Systematic Evaluation of ML vs. Foundation Models for text and image based Medical Classification

The combination of multimodal Vision-Language Models (VLMs) and Large Language Models (LLMs) opens up new possibilities for medical classification. This work offers a rigorous, unified benchmark by using four publicly available datasets covering text and image modalities (binary and multiclass complexity) that contrasts traditional Machine Learning (ML) with contemporary transformer-based techniques. We evaluated three model classes for each task: Classical ML (LR, LightGBM, ResNet-50), Prompt-Based LLMs/VLMs (Gemini 2.5), and Fine-Tuned PEFT Models (LoRA-adapted Gemma3 variants). All experiments used consistent data splits and aligned metrics. According to our results, traditional machine learning (ML) models set a high standard by consistently achieving the best overall performance across most medical categorization tasks. This was especially true for structured text-based datasets, where the classical models performed exceptionally well. In stark contrast, the LoRA-tuned Gemma variants consistently showed the worst performance across all text and image experiments, failing to generalize from the minimal fine-tuning provided. However, the zero-shot LLM/VLM pipelines (Gemini 2.5) had mixed results; they performed poorly on text-based tasks, but demonstrated competitive performance on the multiclass image task, matching the classical ResNet-50 baseline. These results demonstrate that in many medical categorization scenarios, established machine learning models continue to be the most reliable option. The experiment suggests that foundation models are not universally superior and that the effectiveness of Parameter-Efficient Fine-Tuning (PEFT) is highly dependent on the adaptation strategy, as minimal fine-tuning proved detrimental in this study.

DermaBench: A Clinician-Annotated Benchmark Dataset for Dermatology Visual Question Answering and Reasoning

Vision-language models (VLMs) are increasingly important in medical applications; however, their evaluation in dermatology remains limited by datasets that focus primarily on image-level classification tasks such as lesion recognition. While valuable for recognition, such datasets cannot assess the full visual understanding, language grounding, and clinical reasoning capabilities of multimodal models. Visual question answering (VQA) benchmarks are required to evaluate how models interpret dermatological images, reason over fine-grained morphology, and generate clinically meaningful descriptions. We introduce DermaBench, a clinician-annotated dermatology VQA benchmark built on the Diverse Dermatology Images (DDI) dataset. DermaBench comprises 656 clinical images from 570 unique patients spanning Fitzpatrick skin types I-VI. Using a hierarchical annotation schema with 22 main questions (single-choice, multi-choice, and open-ended), expert dermatologists annotated each image for diagnosis, anatomic site, lesion morphology, distribution, surface features, color, and image quality, together with open-ended narrative descriptions and summaries, yielding approximately 14.474 VQA-style annotations. DermaBench is released as a metadata-only dataset to respect upstream licensing and is publicly available at Harvard Dataverse.

Evaluating the Diagnostic Classification Ability of Multimodal Large Language Models: Insights from the Osteoarthritis Initiative

Multimodal large language models (MLLMs) show promising performance on medical visual question answering (VQA) and report generation, but these generation and explanation abilities do not reliably transfer to disease-specific classification. We evaluated MLLM architectures on knee osteoarthritis (OA) radiograph classification, which remains underrepresented in existing medical MLLM benchmarks, even though knee OA affects an estimated 300 to 400 million people worldwide. Through systematic ablation studies manipulating the vision encoder, the connector, and the large language model (LLM) across diverse training strategies, we measured each component's contribution to diagnostic accuracy. In our classification task, a trained vision encoder alone could outperform full MLLM pipelines in classification accuracy and fine-tuning the LLM provided no meaningful improvement over prompt-based guidance. And LoRA fine-tuning on a small, class-balanced dataset (500 images) gave better results than training on a much larger but class-imbalanced set (5,778 images), indicating that data balance and quality can matter more than raw scale for this task. These findings suggest that for domain-specific medical classification, LLMs are more effective as interpreters and report generators rather than as primary classifiers. Therefore, the MLLM architecture appears less suitable for medical image diagnostic classification tasks that demand high certainty. We recommend prioritizing vision encoder optimization and careful dataset curation when developing clinically applicable systems.

MedGemma vs GPT-4: Open-Source and Proprietary Zero-shot Medical Disease Classification from Images

Multimodal Large Language Models (LLMs) introduce an emerging paradigm for medical imaging by interpreting scans through the lens of extensive clinical knowledge, offering a transformative approach to disease classification. This study presents a critical comparison between two fundamentally different AI architectures: the specialized open-source agent MedGemma and the proprietary large multimodal model GPT-4 for diagnosing six different diseases. The MedGemma-4b-it model, fine-tuned using Low-Rank Adaptation (LoRA), demonstrated superior diagnostic capability by achieving a mean test accuracy of 80.37% compared to 69.58% for the untuned GPT-4. Furthermore, MedGemma exhibited notably higher sensitivity in high-stakes clinical tasks, such as cancer and pneumonia detection. Quantitative analysis via confusion matrices and classification reports provides comprehensive insights into model performance across all categories. These results emphasize that domain-specific fine-tuning is essential for minimizing hallucinations in clinical implementation, positioning MedGemma as a sophisticated tool for complex, evidence-based medical reasoning.

Bridging the Perception-Cognition Gap:Re-engineering SAM2 with Hilbert-Mamba for Robust VLM-based Medical Diagnosis

Recent studies suggest that Visual Language Models (VLMs) hold great potential for tasks such as automated medical diagnosis. However, processing complex three-dimensional (3D) multimodal medical images poses significant challenges - specifically, the effective integration of complementary information and the occasional oversight of subtle yet critical pathological features. To address these issues, we present a novel two-stage fusion framework termed Hilbert-VLM. This framework leverages the HilbertMed-SAM module for precise lesion segmentation, with the generated multimodal enhanced prompts then guiding the VLM toward accurate disease classification. Our key innovation lies in the systematic redesign of the Segment Anything Model 2 (SAM2) architecture: we incorporate Hilbert space-filling curves into the scanning mechanism of the Mamba State Space Model (SSM) to maximize the preservation of spatial locality in 3D data, a property critical for medical image analysis. We also introduce a novel Hilbert-Mamba Cross-Attention (HMCA) mechanism and a scale-aware decoder to capture fine-grained details. Meanwhile, the prompt enhancement module unifies segmentation masks and their corresponding textual attributes into an information-dense prompt to support VLM inference. Extensive experiments were conducted to validate the effectiveness of the Hilbert-VLM model. On the BraTS2021 segmentation benchmark, it achieves a Dice score of 82.35 percent, with a diagnostic classification accuracy (ACC) of 78.85 percent. These results demonstrate that the proposed model offers substantial potential to improve the accuracy and reliability of medical VLM-based analysis.

Intersectional Fairness in Vision-Language Models for Medical Image Disease Classification

Medical artificial intelligence (AI) systems, particularly multimodal vision-language models (VLM), often exhibit intersectional biases where models are systematically less confident in diagnosing marginalised patient subgroups. Such bias can lead to higher rates of inaccurate and missed diagnoses due to demographically skewed data and divergent distributions of diagnostic certainty. Current fairness interventions frequently fail to address these gaps or compromise overall diagnostic performance to achieve statistical parity among the subgroups. In this study, we developed Cross-Modal Alignment Consistency (CMAC-MMD), a training framework that standardises diagnostic certainty across intersectional patient subgroups. Unlike traditional debiasing methods, this approach equalises the model's decision confidence without requiring sensitive demographic data during clinical inference. We evaluated this approach using 10,015 skin lesion images (HAM10000) with external validation on 12,000 images (BCN20000), and 10,000 fundus images for glaucoma detection (Harvard-FairVLMed), stratifying performance by intersectional age, gender, and race attributes. In the dermatology cohort, the proposed method reduced the overall intersectional missed diagnosis gap (difference in True Positive Rate, $Δ$TPR) from 0.50 to 0.26 while improving the overall Area Under the Curve (AUC) from 0.94 to 0.97 compared to standard training. Similarly, for glaucoma screening, the method reduced $Δ$TPR from 0.41 to 0.31, achieving a better AUC of 0.72 (vs. 0.71 baseline). This establishes a scalable framework for developing high-stakes clinical decision support systems that are both accurate and can perform equitably across diverse patient subgroups, ensuring reliable performance without increasing privacy risks.

The Multi-View Paradigm Shift in MRI Radiomics: Predicting MGMT Methylation in Glioblastoma

Non-invasive inference of molecular tumor characteristics from medical imaging is a central goal of radiogenomics, particularly in glioblastoma (GBM), where O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation carries important prognostic and therapeutic significance. Although radiomics-based machine learning methods have shown promise for this task, conventional unimodal and early-fusion approaches are often limited by high feature redundancy and an incomplete modeling of modality-specific information. In this work, we introduce a multi-view latent representation learning framework based on variational autoencoders (VAE) to integrate complementary radiomic features derived from post-contrast T1-weighted (T1Gd) and Fluid-Attenuated Inversion Recovery (FLAIR) magnetic resonance imaging (MRI). By encoding each modality through an independent probabilistic encoder and performing fusion in a compact latent space, the proposed approach preserves modality-specific structure while enabling effective multimodal integration. The resulting latent embeddings are subsequently used for MGMT promoter methylation classification.

Beyond CLIP: Knowledge-Enhanced Multimodal Transformers for Cross-Modal Alignment in Diabetic Retinopathy Diagnosis

Diabetic retinopathy (DR) is a leading cause of preventable blindness worldwide, demanding accurate automated diagnostic systems. While general-domain vision-language models like Contrastive Language-Image Pre-Training (CLIP) perform well on natural image tasks, they struggle in medical domain applications, particularly in cross-modal retrieval for ophthalmological images. We propose a novel knowledge-enhanced joint embedding framework that integrates retinal fundus images, clinical text, and structured patient data through a multimodal transformer architecture to address the critical gap in medical image-text alignment. Our approach employs separate encoders for each modality: a Vision Transformer (ViT-B/16) for retinal images, Bio-ClinicalBERT for clinical narratives, and a multilayer perceptron for structured demographic and clinical features. These modalities are fused through a joint transformer with modality-specific embeddings, trained using multiple objectives including contrastive losses between modality pairs, reconstruction losses for images and text, and classification losses for DR severity grading according to ICDR and SDRG schemes. Experimental results on the Brazilian Multilabel Ophthalmological Dataset (BRSET) demonstrate significant improvements over baseline models. Our framework achieves near-perfect text-to-image retrieval performance with Recall@1 of 99.94% compared to fine-tuned CLIP's 1.29%, while maintaining state-of-the-art classification accuracy of 97.05% for SDRG and 97.97% for ICDR. Furthermore, zero-shot evaluation on the unseen DeepEyeNet dataset validates strong generalizability with 93.95% Recall@1 versus 0.22% for fine-tuned CLIP. These results demonstrate that our multimodal training approach effectively captures cross-modal relationships in the medical domain, establishing both superior retrieval capabilities and robust diagnostic performance.