REMEMBER: Retrieval-based Explainable Multimodal Evidence-guided Modeling for Brain Evaluation and Reasoning in Zero- and Few-shot Neurodegenerative Diagnosis

Timely and accurate diagnosis of neurodegenerative disorders, such as Alzheimer's disease, is central to disease management. Existing deep learning models require large-scale annotated datasets and often function as "black boxes". Additionally, datasets in clinical practice are frequently small or unlabeled, restricting the full potential of deep learning methods. Here, we introduce REMEMBER -- Retrieval-based Explainable Multimodal Evidence-guided Modeling for Brain Evaluation and Reasoning -- a new machine learning framework that facilitates zero- and few-shot Alzheimer's diagnosis using brain MRI scans through a reference-based reasoning process. Specifically, REMEMBER first trains a contrastively aligned vision-text model using expert-annotated reference data and extends pseudo-text modalities that encode abnormality types, diagnosis labels, and composite clinical descriptions. Then, at inference time, REMEMBER retrieves similar, human-validated cases from a curated dataset and integrates their contextual information through a dedicated evidence encoding module and attention-based inference head. Such an evidence-guided design enables REMEMBER to imitate real-world clinical decision-making process by grounding predictions in retrieved imaging and textual context. Specifically, REMEMBER outputs diagnostic predictions alongside an interpretable report, including reference images and explanations aligned with clinical workflows. Experimental results demonstrate that REMEMBER achieves robust zero- and few-shot performance and offers a powerful and explainable framework to neuroimaging-based diagnosis in the real world, especially under limited data.

VisTA: Vision-Text Alignment Model with Contrastive Learning using Multimodal Data for Evidence-Driven, Reliable, and Explainable Alzheimer's Disease Diagnosis

Objective: Assessing Alzheimer's disease (AD) using high-dimensional radiology images is clinically important but challenging. Although Artificial Intelligence (AI) has advanced AD diagnosis, it remains unclear how to design AI models embracing predictability and explainability. Here, we propose VisTA, a multimodal language-vision model assisted by contrastive learning, to optimize disease prediction and evidence-based, interpretable explanations for clinical decision-making. Methods: We developed VisTA (Vision-Text Alignment Model) for AD diagnosis. Architecturally, we built VisTA from BiomedCLIP and fine-tuned it using contrastive learning to align images with verified abnormalities and their descriptions. To train VisTA, we used a constructed reference dataset containing images, abnormality types, and descriptions verified by medical experts. VisTA produces four outputs: predicted abnormality type, similarity to reference cases, evidence-driven explanation, and final AD diagnoses. To illustrate VisTA's efficacy, we reported accuracy metrics for abnormality retrieval and dementia prediction. To demonstrate VisTA's explainability, we compared its explanations with human experts' explanations. Results: Compared to 15 million images used for baseline pretraining, VisTA only used 170 samples for fine-tuning and obtained significant improvement in abnormality retrieval and dementia prediction. For abnormality retrieval, VisTA reached 74% accuracy and an AUC of 0.87 (26% and 0.74, respectively, from baseline models). For dementia prediction, VisTA achieved 88% accuracy and an AUC of 0.82 (30% and 0.57, respectively, from baseline models). The generated explanations agreed strongly with human experts' and provided insights into the diagnostic process. Taken together, VisTA optimize prediction, clinical reasoning, and explanation.