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Jan 6

Brain Latent Progression: Individual-based Spatiotemporal Disease Progression on 3D Brain MRIs via Latent Diffusion

The growing availability of longitudinal Magnetic Resonance Imaging (MRI) datasets has facilitated Artificial Intelligence (AI)-driven modeling of disease progression, making it possible to predict future medical scans for individual patients. However, despite significant advancements in AI, current methods continue to face challenges including achieving patient-specific individualization, ensuring spatiotemporal consistency, efficiently utilizing longitudinal data, and managing the substantial memory demands of 3D scans. To address these challenges, we propose Brain Latent Progression (BrLP), a novel spatiotemporal model designed to predict individual-level disease progression in 3D brain MRIs. The key contributions in BrLP are fourfold: (i) it operates in a small latent space, mitigating the computational challenges posed by high-dimensional imaging data; (ii) it explicitly integrates subject metadata to enhance the individualization of predictions; (iii) it incorporates prior knowledge of disease dynamics through an auxiliary model, facilitating the integration of longitudinal data; and (iv) it introduces the Latent Average Stabilization (LAS) algorithm, which (a) enforces spatiotemporal consistency in the predicted progression at inference time and (b) allows us to derive a measure of the uncertainty for the prediction at the global and voxel level. We train and evaluate BrLP on 11,730 T1-weighted (T1w) brain MRIs from 2,805 subjects and validate its generalizability on an external test set comprising 2,257 MRIs from 962 subjects. Our experiments compare BrLP-generated MRI scans with real follow-up MRIs, demonstrating state-of-the-art accuracy compared to existing methods. The code is publicly available at: https://github.com/LemuelPuglisi/BrLP.

  • 3 authors
·
Feb 12, 2025

HR-VILAGE-3K3M: A Human Respiratory Viral Immunization Longitudinal Gene Expression Dataset for Systems Immunity

Respiratory viral infections pose a global health burden, yet the cellular immune responses driving protection or pathology remain unclear. Natural infection cohorts often lack pre-exposure baseline data and structured temporal sampling. In contrast, inoculation and vaccination trials generate insightful longitudinal transcriptomic data. However, the scattering of these datasets across platforms, along with inconsistent metadata and preprocessing procedure, hinders AI-driven discovery. To address these challenges, we developed the Human Respiratory Viral Immunization LongitudinAl Gene Expression (HR-VILAGE-3K3M) repository: an AI-ready, rigorously curated dataset that integrates 14,136 RNA-seq profiles from 3,178 subjects across 66 studies encompassing over 2.56 million cells. Spanning vaccination, inoculation, and mixed exposures, the dataset includes microarray, bulk RNA-seq, and single-cell RNA-seq from whole blood, PBMCs, and nasal swabs, sourced from GEO, ImmPort, and ArrayExpress. We harmonized subject-level metadata, standardized outcome measures, applied unified preprocessing pipelines with rigorous quality control, and aligned all data to official gene symbols. To demonstrate the utility of HR-VILAGE-3K3M, we performed predictive modeling of vaccine responders and evaluated batch-effect correction methods. Beyond these initial demonstrations, it supports diverse systems immunology applications and benchmarking of feature selection and transfer learning algorithms. Its scale and heterogeneity also make it ideal for pretraining foundation models of the human immune response and for advancing multimodal learning frameworks. As the largest longitudinal transcriptomic resource for human respiratory viral immunization, it provides an accessible platform for reproducible AI-driven research, accelerating systems immunology and vaccine development against emerging viral threats.

  • 17 authors
·
May 19, 2025