A Quantitative Analysis of Multimodal Biomarkers in Alzheimer's DiseaseAntonio Scardace, Daniele Ravì
Despite increasing adoption of multimodal approaches in Alzheimer's Disease (AD) research -- aimed at integrating molecular, structural, clinical, and genetic biomarkers to enhance disease characterization -- the relationships among these modalities remain poorly understood. A systematic analysis of their dynamic interaction is essential for improving disease modeling, identifying redundant assessments, and reducing patient burden and acquisition costs. In this paper, we present a quantitative analysis of multimodal AD biomarkers by integrating tau-PET, structural MRI, cognitive scores (MMSE and CDR), and APOE4 data from 789 subjects drawn from the ADNI dataset. In our analyses, we (A) quantify cross-modal mutual information and explained variance to assess redundancy and predictive dependencies; (B) examine associations between tau topologies and structural atrophy across brain regions to select informative ROIs; (C) perform a statistical decomposition of the tau-cognition association into atrophy-related and atrophy-independent components; (D) and identify a dominant neurodegenerative trajectory that aligns with cognitive decline. This study provides a systematic characterization of cross-modal relationships, improving the interpretability and selection of biomarkers in AD. Code is publicly available at: https://github.com/antonioscardace/Multimodal-AD.
A Novel Metric for Detecting Memorization in Generative Models for Brain MRI SynthesisAntonio Scardace, Lemuel Puglisi, Francesco Guarnera et al.
Deep generative models have emerged as a transformative tool in medical imaging, offering substantial potential for synthetic data generation. However, recent empirical studies highlight a critical vulnerability: these models can memorize sensitive training data, posing significant risks of unauthorized patient information disclosure. Detecting memorization in generative models remains particularly challenging, necessitating scalable methods capable of identifying training data leakage across large sets of generated samples. In this work, we propose DeepSSIM, a novel self-supervised metric for quantifying memorization in generative models. DeepSSIM is trained to: i) project images into a learned embedding space and ii) force the cosine similarity between embeddings to match the ground-truth SSIM (Structural Similarity Index) scores computed in the image space. To capture domain-specific anatomical features, training incorporates structure-preserving augmentations, allowing DeepSSIM to estimate similarity reliably without requiring precise spatial alignment. We evaluate DeepSSIM in a case study involving synthetic brain MRI data generated by a Latent Diffusion Model (LDM) trained under memorization-prone conditions, using 2,195 MRI scans from two publicly available datasets (IXI and CoRR). Compared to state-of-the-art memorization metrics, DeepSSIM achieves superior performance, improving F1 scores by an average of +52.03% over the best existing method. Code and data of our approach are publicly available at the following link: https://github.com/brAIn-science/DeepSSIM.