Ke Zou

Meng Wang, Lianyu Wang, Xinxing Xu et al.

Deep learning models have shown promising performance in the field of diabetic retinopathy (DR) staging. However, collaboratively training a DR staging model across multiple institutions remains a challenge due to non-iid data, client reliability, and confidence evaluation of the prediction. To address these issues, we propose a novel federated uncertainty-aware aggregation paradigm (FedUAA), which considers the reliability of each client and produces a confidence estimation for the DR staging. In our FedUAA, an aggregated encoder is shared by all clients for learning a global representation of fundus images, while a novel temperature-warmed uncertainty head (TWEU) is utilized for each client for local personalized staging criteria. Our TWEU employs an evidential deep layer to produce the uncertainty score with the DR staging results for client reliability evaluation. Furthermore, we developed a novel uncertainty-aware weighting module (UAW) to dynamically adjust the weights of model aggregation based on the uncertainty score distribution of each client. In our experiments, we collect five publicly available datasets from different institutions to conduct a dataset for federated DR staging to satisfy the real non-iid condition. The experimental results demonstrate that our FedUAA achieves better DR staging performance with higher reliability compared to other federated learning methods. Our proposed FedUAA paradigm effectively addresses the challenges of collaboratively training DR staging models across multiple institutions, and provides a robust and reliable solution for the deployment of DR diagnosis models in real-world clinical scenarios.

Samantha Min Er Yew, Xiaofeng Lei, Jocelyn Hui Lin Goh et al.

Background: RETFound, a self-supervised, retina-specific foundation model (FM), showed potential in downstream applications. However, its comparative performance with traditional deep learning (DL) models remains incompletely understood. This study aimed to evaluate RETFound against three ImageNet-pretrained supervised DL models (ResNet50, ViT-base, SwinV2) in detecting ocular and systemic diseases. Methods: We fine-tuned/trained RETFound and three DL models on full datasets, 50%, 20%, and fixed sample sizes (400, 200, 100 images, with half comprising disease cases; for each DR severity class, 100 and 50 cases were used. Fine-tuned models were tested internally using the SEED (53,090 images) and APTOS-2019 (3,672 images) datasets and externally validated on population-based (BES, CIEMS, SP2, UKBB) and open-source datasets (ODIR-5k, PAPILA, GAMMA, IDRiD, MESSIDOR-2). Model performance was compared using area under the receiver operating characteristic curve (AUC) and Z-tests with Bonferroni correction (P<0.05/3). Interpretation: Traditional DL models are mostly comparable to RETFound for ocular disease detection with large datasets. However, RETFound is superior in systemic disease detection with smaller datasets. These findings offer valuable insights into the respective merits and limitation of traditional models and FMs.

Ke Zou, Yang Bai, Bo Liu et al.

Medical phrase grounding is crucial for identifying relevant regions in medical images based on phrase queries, facilitating accurate image analysis and diagnosis. However, current methods rely on manual extraction of key phrases from medical reports, reducing efficiency and increasing the workload for clinicians. Additionally, the lack of model confidence estimation limits clinical trust and usability. In this paper, we introduce a novel task called Medical Report Grounding (MRG), which aims to directly identify diagnostic phrases and their corresponding grounding boxes from medical reports in an end-to-end manner. To address this challenge, we propose uMedGround, a robust and reliable framework that leverages a multimodal large language model to predict diagnostic phrases by embedding a unique token, <BOX>, into the vocabulary to enhance detection capabilities. A vision encoder-decoder processes the embedded token and input image to generate grounding boxes. Critically, uMedGround incorporates an uncertainty-aware prediction model, significantly improving the robustness and reliability of grounding predictions. Experimental results demonstrate that uMedGround outperforms state-of-the-art medical phrase grounding methods and fine-tuned large visual-language models, validating its effectiveness and reliability. This study represents a pioneering exploration of the MRG task, marking the first-ever endeavor in this domain. Additionally, we demonstrate the applicability of uMedGround in medical visual question answering and class-based localization tasks, where it highlights visual evidence aligned with key diagnostic phrases, supporting clinicians in interpreting various types of textual inputs, including free-text reports, visual question answering queries, and class labels.

Zehui Liao, Shishuai Hu, Ke Zou et al.

Multimodal large language models (MLLMs) have demonstrated significant potential in medical Visual Question Answering (VQA). Yet, they remain prone to hallucinations-incorrect responses that contradict input images, posing substantial risks in clinical decision-making. Detecting these hallucinations is essential for establishing trust in MLLMs among clinicians and patients, thereby enabling their real-world adoption. Current hallucination detection methods, especially semantic entropy (SE), have demonstrated promising hallucination detection capacity for LLMs. However, adapting SE to medical MLLMs by incorporating visual perturbations presents a dilemma. Weak perturbations preserve image content and ensure clinical validity, but may be overlooked by medical MLLMs, which tend to over rely on language priors. In contrast, strong perturbations can distort essential diagnostic features, compromising clinical interpretation. To address this issue, we propose Vision Amplified Semantic Entropy (VASE), which incorporates weak image transformations and amplifies the impact of visual input, to improve hallucination detection in medical VQA. We first estimate the semantic predictive distribution under weak visual transformations to preserve clinical validity, and then amplify visual influence by contrasting this distribution with that derived from a distorted image. The entropy of the resulting distribution is estimated as VASE. Experiments on two medical open-ended VQA datasets demonstrate that VASE consistently outperforms existing hallucination detection methods.

Qingshan Hou, Meng Wang, Peng Cao et al.

Recent advancements in ophthalmology foundation models such as RetFound have demonstrated remarkable diagnostic capabilities but require massive datasets for effective pre-training, creating significant barriers for development and deployment. To address this critical challenge, we propose FundusGAN, a novel hierarchical feature-aware generative framework specifically designed for high-fidelity fundus image synthesis. Our approach leverages a Feature Pyramid Network within its encoder to comprehensively extract multi-scale information, capturing both large anatomical structures and subtle pathological features. The framework incorporates a modified StyleGAN-based generator with dilated convolutions and strategic upsampling adjustments to preserve critical retinal structures while enhancing pathological detail representation. Comprehensive evaluations on the DDR, DRIVE, and IDRiD datasets demonstrate that FundusGAN consistently outperforms state-of-the-art methods across multiple metrics (SSIM: 0.8863, FID: 54.2, KID: 0.0436 on DDR). Furthermore, disease classification experiments reveal that augmenting training data with FundusGAN-generated images significantly improves diagnostic accuracy across multiple CNN architectures (up to 6.49\% improvement with ResNet50). These results establish FundusGAN as a valuable foundation model component that effectively addresses data scarcity challenges in ophthalmological AI research, enabling more robust and generalizable diagnostic systems while reducing dependency on large-scale clinical data collection.

Sahana Srinivasan, Xuguang Ai, Minjie Zou et al.

Question: What is the performance and reasoning ability of OpenAI o1 compared to other large language models in addressing ophthalmology-specific questions? Findings: This study evaluated OpenAI o1 and five LLMs using 6,990 ophthalmological questions from MedMCQA. O1 achieved the highest accuracy (0.88) and macro-F1 score but ranked third in reasoning capabilities based on text-generation metrics. Across subtopics, o1 ranked first in ``Lens'' and ``Glaucoma'' but second to GPT-4o in ``Corneal and External Diseases'', ``Vitreous and Retina'' and ``Oculoplastic and Orbital Diseases''. Subgroup analyses showed o1 performed better on queries with longer ground truth explanations. Meaning: O1's reasoning enhancements may not fully extend to ophthalmology, underscoring the need for domain-specific refinements to optimize performance in specialized fields like ophthalmology.

Minjie Zou, Sahana Srinivasan, Thaddaeus Wai Soon Lo et al.

Recent advances in reasoning-focused large language models (LLMs) mark a shift from general LLMs toward models designed for complex decision-making, a crucial aspect in medicine. However, their performance in specialized domains like ophthalmology remains underexplored. This study comprehensively evaluated and compared the accuracy and reasoning capabilities of four newly developed reasoning-focused LLMs, namely DeepSeek-R1, OpenAI o1, o3-mini, and Gemini 2.0 Flash-Thinking. Each model was assessed using 5,888 multiple-choice ophthalmology exam questions from the MedMCQA dataset in zero-shot setting. Quantitative evaluation included accuracy, Macro-F1, and five text-generation metrics (ROUGE-L, METEOR, BERTScore, BARTScore, and AlignScore), computed against ground-truth reasonings. Average inference time was recorded for a subset of 100 randomly selected questions. Additionally, two board-certified ophthalmologists qualitatively assessed clarity, completeness, and reasoning structure of responses to differential diagnosis questions.O1 (0.902) and DeepSeek-R1 (0.888) achieved the highest accuracy, with o1 also leading in Macro-F1 (0.900). The performance of models across the text-generation metrics varied: O3-mini excelled in ROUGE-L (0.151), o1 in METEOR (0.232), DeepSeek-R1 and o3-mini tied for BERTScore (0.673), DeepSeek-R1 (-4.105) and Gemini 2.0 Flash-Thinking (-4.127) performed best in BARTScore, while o3-mini (0.181) and o1 (0.176) led AlignScore. Inference time across the models varied, with DeepSeek-R1 being slowest (40.4 seconds) and Gemini 2.0 Flash-Thinking fastest (6.7 seconds). Qualitative evaluation revealed that DeepSeek-R1 and Gemini 2.0 Flash-Thinking tended to provide detailed and comprehensive intermediate reasoning, whereas o1 and o3-mini displayed concise and summarized justifications.

Meng Wang, Tian Lin, Qingshan Hou et al.

Artificial intelligence (AI) shows remarkable potential in medical imaging diagnostics, yet most current models require retraining when applied across different clinical settings, limiting their scalability. We introduce GlobeReady, a clinician-friendly AI platform that enables fundus disease diagnosis that operates without retraining, fine-tuning, or the needs for technical expertise. GlobeReady demonstrates high accuracy across imaging modalities: 93.9-98.5% for 11 fundus diseases using color fundus photographs (CPFs) and 87.2-92.7% for 15 fundus diseases using optic coherence tomography (OCT) scans. By leveraging training-free local feature augmentation, GlobeReady platform effectively mitigates domain shifts across centers and populations, achieving accuracies of 88.9-97.4% across five centers on average in China, 86.3-96.9% in Vietnam, and 73.4-91.0% in Singapore, and 90.2-98.9% in the UK. Incorporating a bulit-in confidence-quantifiable diagnostic mechanism further enhances the platform's accuracy to 94.9-99.4% with CFPs and 88.2-96.2% with OCT, while enabling identification of out-of-distribution cases with 86.3% accuracy across 49 common and rare fundus diseases using CFPs, and 90.6% accuracy across 13 diseases using OCT. Clinicians from countries rated GlobeReady highly for usability and clinical relevance (average score 4.6/5). These findings demonstrate GlobeReady's robustness, generalizability and potential to support global ophthalmic care without technical barriers.

Sahana Srinivasan, Xuguang Ai, Thaddaeus Wai Soon Lo et al.

Current benchmarks evaluating large language models (LLMs) in ophthalmology are limited in scope and disproportionately prioritise accuracy. We introduce BELO (BEnchmarking LLMs for Ophthalmology), a standardized and comprehensive evaluation benchmark developed through multiple rounds of expert checking by 13 ophthalmologists. BELO assesses ophthalmology-related clinical accuracy and reasoning quality. Using keyword matching and a fine-tuned PubMedBERT model, we curated ophthalmology-specific multiple-choice-questions (MCQs) from diverse medical datasets (BCSC, MedMCQA, MedQA, BioASQ, and PubMedQA). The dataset underwent multiple rounds of expert checking. Duplicate and substandard questions were systematically removed. Ten ophthalmologists refined the explanations of each MCQ's correct answer. This was further adjudicated by three senior ophthalmologists. To illustrate BELO's utility, we evaluated six LLMs (OpenAI o1, o3-mini, GPT-4o, DeepSeek-R1, Llama-3-8B, and Gemini 1.5 Pro) using accuracy, macro-F1, and five text-generation metrics (ROUGE-L, BERTScore, BARTScore, METEOR, and AlignScore). In a further evaluation involving human experts, two ophthalmologists qualitatively reviewed 50 randomly selected outputs for accuracy, comprehensiveness, and completeness. BELO consists of 900 high-quality, expert-reviewed questions aggregated from five sources: BCSC (260), BioASQ (10), MedMCQA (572), MedQA (40), and PubMedQA (18). A public leaderboard has been established to promote transparent evaluation and reporting. Importantly, the BELO dataset will remain a hold-out, evaluation-only benchmark to ensure fair and reproducible comparisons of future models.

Hongye Zeng, Ke Zou, Zhihao Chen et al.

Handheld ultrasound devices face usage limitations due to user inexperience and cannot benefit from supervised deep learning without extensive expert annotations. Moreover, the models trained on standard ultrasound device data are constrained by training data distribution and perform poorly when directly applied to handheld device data. In this study, we propose the Training-free Image Style Alignment (TISA) framework to align the style of handheld device data to those of standard devices. The proposed TISA can directly infer handheld device images without extra training and is suited for clinical applications. We show that TISA performs better and more stably in medical detection and segmentation tasks for handheld device data. We further validate TISA as the clinical model for automatic measurements of spinal curvature and carotid intima-media thickness. The automatic measurements agree well with manual measurements made by human experts and the measurement errors remain within clinically acceptable ranges. We demonstrate the potential for TISA to facilitate automatic diagnosis on handheld ultrasound devices and expedite their eventual widespread use.

Guoyao Deng, Ke Zou, Kai Ren et al.

Recently, Segmenting Anything has taken an important step towards general artificial intelligence. At the same time, its reliability and fairness have also attracted great attention, especially in the field of health care. In this study, we propose multi-box prompts triggered uncertainty estimation for SAM cues to demonstrate the reliability of segmented lesions or tissues. We estimate the distribution of SAM predictions via Monte Carlo with prior distribution parameters, which employs different prompts as formulation of test-time augmentation. Our experimental results found that multi-box prompts augmentation improve the SAM performance, and endowed each pixel with uncertainty. This provides the first paradigm for a reliable SAM.