Luis Filipe Nakayama

Sebastian Cajas, Ashaba Judith, Rahul Gorijavolu et al.

Latent diffusion models for medical image super-resolution universally inherit variational autoencoders designed for natural photographs. We show that this default choice, not the diffusion architecture, is the dominant constraint on reconstruction quality. In a controlled experiment holding all other pipeline components fixed, replacing the generic Stable Diffusion VAE with MedVAE, a domain-specific autoencoder pretrained on more than 1.6 million medical images, yields +2.91 to +3.29 dB PSNR improvement across knee MRI, brain MRI, and chest X-ray (n = 1,820; Cohen's d = 1.37 to 1.86, all p < 10^{-20}, Wilcoxon signed-rank). Wavelet decomposition localises the advantage to the finest spatial frequency bands encoding anatomically relevant fine structure. Ablations across inference schedules, prediction targets, and generative architectures confirm the gap is stable within plus or minus 0.15 dB, while hallucination rates remain comparable between methods (Cohen's h < 0.02 across all datasets), establishing that reconstruction fidelity and generative hallucination are governed by independent pipeline components. These results provide a practical screening criterion: autoencoder reconstruction quality, measurable without diffusion training, predicts downstream SR performance (R^2 = 0.67), suggesting that domain-specific VAE selection should precede diffusion architecture search. Code and trained model weights are publicly available at https://github.com/sebasmos/latent-sr.

David Restrepo, Miguel L Martins, Chenwei Wu et al.

Vision-Language Models (VLMs) exhibit a characteristic "cone effect" in which nonlinear encoders map embeddings into highly concentrated regions of the representation space, contributing to cross-modal separation known as the modality gap. While this phenomenon has been widely observed, its practical impact on supervised multimodal learning -particularly in medical domains- remains unclear. In this work, we introduce a lightweight post-hoc mechanism that keeps pretrained VLM encoders frozen while continuously controlling cross-modal separation through a single hyperparameter {λ}. This enables systematic analysis of how the modality gap affects downstream multimodal performance without expensive retraining. We evaluate generalist (CLIP, SigLIP) and medically specialized (BioMedCLIP, MedSigLIP) models across diverse medical and natural datasets in a supervised multimodal settings. Results consistently show that reducing excessive modality gap improves downstream performance, with medical datasets exhibiting stronger sensitivity to gap modulation; however, fully collapsing the gap is not always optimal, and intermediate, task-dependent separation yields the best results. These findings position the modality gap as a tunable property of multimodal representations rather than a quantity that should be universally minimized.

Jonathan Fhima, Jan Van Eijgen, Lennert Beeckmans et al.

Generalization in medical segmentation models is challenging due to limited annotated datasets and imaging variability. To address this, we propose Retinal Layout-Aware Diffusion (RLAD), a novel diffusion-based framework for generating controllable layout-aware images. RLAD conditions image generation on multiple key layout components extracted from real images, ensuring high structural fidelity while enabling diversity in other components. Applied to retinal fundus imaging, we augmented the training datasets by synthesizing paired retinal images and vessel segmentations conditioned on extracted blood vessels from real images, while varying other layout components such as lesions and the optic disc. Experiments demonstrated that RLAD-generated data improved generalization in retinal vessel segmentation by up to 8.1%. Furthermore, we present REYIA, a comprehensive dataset comprising 586 manually segmented retinal images. To foster reproducibility and drive innovation, both our code and dataset will be made publicly accessible.

Dilermando Queiroz, Anderson Carlos, Maíra Fatoretto et al.

Foundation models have emerged as robust models with label efficiency in diverse domains. In medical imaging, these models contribute to the advancement of medical diagnoses due to the difficulty in obtaining labeled data. However, it is unclear whether using a large amount of unlabeled data, biased by the presence of sensitive attributes during pre-training, influences the fairness of the model. This research examines the bias in the Foundation model (RetFound) when it is applied to fine-tune the Brazilian Multilabel Ophthalmological Dataset (BRSET), which has a different population than the pre-training dataset. The model evaluation, in comparison with supervised learning, shows that the Foundation Model has the potential to reduce the gap between the maximum AUC and minimum AUC evaluations across gender and age groups. However, in a data-efficient generalization, the model increases the bias when the data amount decreases. These findings suggest that when deploying a Foundation Model in real-life scenarios with limited data, the possibility of fairness issues should be considered.

David Restrepo, Chenwei Wu, Constanza Vásquez-Venegas et al.

In the big data era, integrating diverse data modalities poses significant challenges, particularly in complex fields like healthcare. This paper introduces a new process model for multimodal Data Fusion for Data Mining, integrating embeddings and the Cross-Industry Standard Process for Data Mining with the existing Data Fusion Information Group model. Our model aims to decrease computational costs, complexity, and bias while improving efficiency and reliability. We also propose "disentangled dense fusion", a novel embedding fusion method designed to optimize mutual information and facilitate dense inter-modality feature interaction, thereby minimizing redundant information. We demonstrate the model's efficacy through three use cases: predicting diabetic retinopathy using retinal images and patient metadata, domestic violence prediction employing satellite imagery, internet, and census data, and identifying clinical and demographic features from radiography images and clinical notes. The model achieved a Macro F1 score of 0.92 in diabetic retinopathy prediction, an R-squared of 0.854 and sMAPE of 24.868 in domestic violence prediction, and a macro AUC of 0.92 and 0.99 for disease prediction and sex classification, respectively, in radiological analysis. These results underscore the Data Fusion for Data Mining model's potential to significantly impact multimodal data processing, promoting its adoption in diverse, resource-constrained settings.

Yevgeniy Men, Jonathan Fhima, Leo Anthony Celi et al.

Diabetic retinopathy (DR) is a prevalent complication of diabetes associated with a significant risk of vision loss. Timely identification is critical to curb vision impairment. Algorithms for DR staging from digital fundus images (DFIs) have been recently proposed. However, models often fail to generalize due to distribution shifts between the source domain on which the model was trained and the target domain where it is deployed. A common and particularly challenging shift is often encountered when the source- and target-domain supports do not fully overlap. In this research, we introduce DRStageNet, a deep learning model designed to mitigate this challenge. We used seven publicly available datasets, comprising a total of 93,534 DFIs that cover a variety of patient demographics, ethnicities, geographic origins and comorbidities. We fine-tune DINOv2, a pretrained model of self-supervised vision transformer, and implement a multi-source domain fine-tuning strategy to enhance generalization performance. We benchmark and demonstrate the superiority of our method to two state-of-the-art benchmarks, including a recently published foundation model. We adapted the grad-rollout method to our regression task in order to provide high-resolution explainability heatmaps. The error analysis showed that 59\% of the main errors had incorrect reference labels. DRStageNet is accessible at URL [upon acceptance of the manuscript].

David Restrepo, Chenwei Wu, Zhengxu Tang et al.

Current ophthalmology clinical workflows are plagued by over-referrals, long waits, and complex and heterogeneous medical records. Large language models (LLMs) present a promising solution to automate various procedures such as triaging, preliminary tests like visual acuity assessment, and report summaries. However, LLMs have demonstrated significantly varied performance across different languages in natural language question-answering tasks, potentially exacerbating healthcare disparities in Low and Middle-Income Countries (LMICs). This study introduces the first multilingual ophthalmological question-answering benchmark with manually curated questions parallel across languages, allowing for direct cross-lingual comparisons. Our evaluation of 6 popular LLMs across 7 different languages reveals substantial bias across different languages, highlighting risks for clinical deployment of LLMs in LMICs. Existing debiasing methods such as Translation Chain-of-Thought or Retrieval-augmented generation (RAG) by themselves fall short of closing this performance gap, often failing to improve performance across all languages and lacking specificity for the medical domain. To address this issue, We propose CLARA (Cross-Lingual Reflective Agentic system), a novel inference time de-biasing method leveraging retrieval augmented generation and self-verification. Our approach not only improves performance across all languages but also significantly reduces the multilingual bias gap, facilitating equitable LLM application across the globe.

Leonor Fernandes, Tiago Gonçalves, João Matos et al.

Diabetic retinopathy (DR) is a leading cause of vision loss in working-age adults. While screening reduces the risk of blindness, traditional imaging is often costly and inaccessible. Artificial intelligence (AI) algorithms present a scalable diagnostic solution, but concerns regarding fairness and generalization persist. This work evaluates the fairness and performance of image-trained models in DR prediction, as well as the impact of disentanglement as a bias mitigation technique, using the diverse mBRSET fundus dataset. Three models, ConvNeXt V2, DINOv2, and Swin V2, were trained on macula images to predict DR and sensitive attributes (SAs) (e.g., age and gender/sex). Fairness was assessed between subgroups of SAs, and disentanglement was applied to reduce bias. All models achieved high DR prediction performance in diagnosing (up to 94% AUROC) and could reasonably predict age and gender/sex (91% and 77% AUROC, respectively). Fairness assessment suggests disparities, such as a 10% AUROC gap between age groups in DINOv2. Disentangling SAs from DR prediction had varying results, depending on the model selected. Disentanglement improved DINOv2 performance (2% AUROC gain), but led to performance drops in ConvNeXt V2 and Swin V2 (7% and 3%, respectively). These findings highlight the complexity of disentangling fine-grained features in fundus imaging and emphasize the importance of fairness in medical imaging AI to ensure equitable and reliable healthcare solutions.

Cindy Lie Tabuse, David Restepo, Carolina Gracitelli et al.

Large language models (LLMs) can simulate clinical reasoning based on natural language prompts, but their utility in ophthalmology is largely unexplored. This study evaluated GPT-4's ability to interpret structured textual descriptions of retinal fundus photographs and simulate clinical decisions for diabetic retinopathy (DR) and glaucoma screening, including the impact of adding real or synthetic clinical metadata. We conducted a retrospective diagnostic validation study using 300 annotated fundus images. GPT-4 received structured prompts describing each image, with or without patient metadata. The model was tasked with assigning an ICDR severity score, recommending DR referral, and estimating the cup-to-disc ratio for glaucoma referral. Performance was evaluated using accuracy, macro and weighted F1 scores, and Cohen's kappa. McNemar's test and change rate analysis were used to assess the influence of metadata. GPT-4 showed moderate performance for ICDR classification (accuracy 67.5%, macro F1 0.33, weighted F1 0.67, kappa 0.25), driven mainly by correct identification of normal cases. Performance improved in the binary DR referral task (accuracy 82.3%, F1 0.54, kappa 0.44). For glaucoma referral, performance was poor across all settings (accuracy ~78%, F1 <0.04, kappa <0.03). Metadata inclusion did not significantly affect outcomes (McNemar p > 0.05), and predictions remained consistent across conditions. GPT-4 can simulate basic ophthalmic decision-making from structured prompts but lacks precision for complex tasks. While not suitable for clinical use, LLMs may assist in education, documentation, or image annotation workflows in ophthalmology.

Benjamin A. Cohen, Jonathan Fhima, Meishar Meisel et al.

Self-supervised learning (SSL) has enabled Vision Transformers (ViTs) to learn robust representations from large-scale natural image datasets, enhancing their generalization across domains. In retinal imaging, foundation models pretrained on either natural or ophthalmic data have shown promise, but the benefits of in-domain pretraining remain uncertain. To investigate this, we benchmark six SSL-pretrained ViTs on seven digital fundus image (DFI) datasets totaling 70,000 expert-annotated images for the task of moderate-to-late age-related macular degeneration (AMD) identification. Our results show that iBOT pretrained on natural images achieves the highest out-of-distribution generalization, with AUROCs of 0.80-0.97, outperforming domain-specific models, which achieved AUROCs of 0.78-0.96 and a baseline ViT-L with no pretraining, which achieved AUROCs of 0.68-0.91. These findings highlight the value of foundation models in improving AMD identification and challenge the assumption that in-domain pretraining is necessary. Furthermore, we release BRAMD, an open-access dataset (n=587) of DFIs with AMD labels from Brazil.

Maria Miguel Beirão, João Matos, Tiago Gonçalves et al.

Keratitis is an inflammatory corneal condition responsible for 10% of visual impairment in low- and middle-income countries (LMICs), with bacteria, fungi, or amoeba as the most common infection etiologies. While an accurate and timely diagnosis is crucial for the selected treatment and the patients' sight outcomes, due to the high cost and limited availability of laboratory diagnostics in LMICs, diagnosis is often made by clinical observation alone, despite its lower accuracy. In this study, we investigate and compare different deep learning approaches to diagnose the source of infection: 1) three separate binary models for infection type predictions; 2) a multitask model with a shared backbone and three parallel classification layers (Multitask V1); and, 3) a multitask model with a shared backbone and a multi-head classification layer (Multitask V2). We used a private Brazilian cornea dataset to conduct the empirical evaluation. We achieved the best results with Multitask V2, with an area under the receiver operating characteristic curve (AUROC) confidence intervals of 0.7413-0.7740 (bacteria), 0.8395-0.8725 (fungi), and 0.9448-0.9616 (amoeba). A statistical analysis of the impact of patient features on models' performance revealed that sex significantly affects amoeba infection prediction, and age seems to affect fungi and bacteria predictions.

David Restrepo, Chenwei Wu, Constanza Vásquez-Venegas et al.

The deployment of large language models (LLMs) in healthcare has demonstrated substantial potential for enhancing clinical decision-making, administrative efficiency, and patient outcomes. However, the underrepresentation of diverse groups in the development and application of these models can perpetuate biases, leading to inequitable healthcare delivery. This paper presents a comprehensive scientometric analysis of LLM research for healthcare, including data from January 1, 2021, to July 1, 2024. By analyzing metadata from PubMed and Dimensions, including author affiliations, countries, and funding sources, we assess the diversity of contributors to LLM research. Our findings highlight significant gender and geographic disparities, with a predominance of male authors and contributions primarily from high-income countries (HICs). We introduce a novel journal diversity index based on Gini diversity to measure the inclusiveness of scientific publications. Our results underscore the necessity for greater representation in order to ensure the equitable application of LLMs in healthcare. We propose actionable strategies to enhance diversity and inclusivity in artificial intelligence research, with the ultimate goal of fostering a more inclusive and equitable future in healthcare innovation.

David Restrepo, Chenwei Wu, Sebastián Andrés Cajas et al.

Large-scale multi-modal deep learning models have revolutionized domains such as healthcare, highlighting the importance of computational power. However, in resource-constrained regions like Low and Middle-Income Countries (LMICs), limited access to GPUs and data poses significant challenges, often leaving CPUs as the sole resource. To address this, we advocate for leveraging vector embeddings to enable flexible and efficient computational methodologies, democratizing multimodal deep learning across diverse contexts. Our paper investigates the efficiency and effectiveness of using vector embeddings from single-modal foundation models and multi-modal Vision-Language Models (VLMs) for multimodal deep learning in low-resource environments, particularly in healthcare. Additionally, we propose a simple yet effective inference-time method to enhance performance by aligning image-text embeddings. Comparing these approaches with traditional methods, we assess their impact on computational efficiency and model performance using metrics like accuracy, F1-score, inference time, training time, and memory usage across three medical modalities: BRSET (ophthalmology), HAM10000 (dermatology), and SatelliteBench (public health). Our findings show that embeddings reduce computational demands without compromising model performance. Furthermore, our alignment method improves performance in medical tasks. This research promotes sustainable AI practices by optimizing resources in constrained environments, highlighting the potential of embedding-based approaches for efficient multimodal learning. Vector embeddings democratize multimodal deep learning in LMICs, particularly in healthcare, enhancing AI adaptability in varied use cases.