Federated Learning for MRI-based BrainAGE: a multicenter study on post-stroke functional outcome prediction
Authors: Vincent Roca, Marc Tommasi, Paul Andrey, Aurélien Bellet, Markus D. Schirmer, Hilde Henon, Laurent Puy, Julien Ramon, +3 more
Organizations: Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US 41 - UAR 2014 - PLBS, F-59000 Lille, France · Univ. Lille, Inria, F-59000 Lille, France · Univ. Montpellier, Inria, F-34090 Montpellier, France · Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, USA · CHU Lille, D´epartement de Neurologie vasculaire, F-59037 Lille, France · Univ. Lille, Inserm, CHU Lille, U1172 - Lille Neurosciences & Cognition, F-59037 Lille, France
Abstract
Objective: Brain-predicted age difference (BrainAGE) is a neuroimaging biomarker reflecting brain health. However, training robust BrainAGE models requires large datasets, often restricted by privacy concerns. This study evaluates the performance of federated learning (FL) for BrainAGE estimation in ischemic stroke patients treated with mechanical thrombectomy, and investigates its association with clinical phenotypes and functional outcomes. Methods: We used FLAIR brain images from 1674 stroke patients across 16 hospital centers. We implemented standard machine learning and deep learning models for BrainAGE estimates under three data management strategies: centralized learning (pooled data), FL (local training at each site), and single-site learning. We reported prediction errors and examined associations between BrainAGE and vascular risk factors (e.g., diabetes mellitus, hypertension, smoking), as well as functional outcomes at three months post-stroke. Logistic regression evaluated BrainAGE's predictive value for these outcomes, adjusting for age, sex, vascular risk factors, stroke severity, time between MRI and arterial puncture, prior intravenous thrombolysis, and recanalisation outcome. Results: While centralized learning yielded the most accurate predictions, FL consistently outperformed single-site models. BrainAGE was significantly higher in patients with diabetes mellitus across all models. Comparisons between patients with good and poor functional outcomes, and multivariate predictions of these outcomes showed the significance of the association between BrainAGE and post-stroke recovery. Conclusion: FL enables accurate age predictions without data centralization. The strong association between BrainAGE, vascular risk factors, and post-stroke recovery highlights its potential for prognostic modeling in stroke care.
Aging clocks quantify biological aging and help characterize individual health status. What protein interactions are important for accurate aging clocks, and are they zeroth-order or higher-order? Addressing these questions requires learning from large molecular datasets distributed across medical centers, where privacy constraints prevent centralized data sharing. Federated learning offers a natural solution but faces four challenges in this setting: limited local sample sizes, sparse and directional inter-center trust, the need to retain discriminative age prediction while supporting interpretation, and model drift and forgetting under heterogeneous cross-center data. We propose TNFL, a trust-network-based federated learning framework that progressively propagates models along directed pairwise trust relations without centralized aggregation. TNFL combines an age-aware mixture-of-experts model with generative replay to preserve previously learned information and reduce forgetting and drift. Experiments across multiple molecular datasets show that TNFL enables effective aging-clock prediction with limited local data, provides interpretable age-dependent prediction patterns, and maintains stable performance across interaction orders. To investigate the biological questions, we analyze TNFL-identified pairwise protein interactions and their higher-order organization through functional and network analyses. The identified interactions repeatedly form coordinated higher-order subnetworks spanning multiple aging-related biological systems, with several proteins recurring across subnetworks. These findings suggest that TNFL captures molecular relationships beyond isolated pairwise associations and reveals coherent higher-order biological organization associated with aging.
Federated Learning (FL) enables collaborative training of machine learning models across multiple institutions without sharing sensitive data, making it particularly suitable for medical imaging applications. However, heterogeneous data distributions across institutions and potential information leakage through model updates remain important challenges. In this work, we propose DP-SimAgg, a privacy-preserving federated learning framework that integrates similarity-weighted aggregation with a server-side differential privacy mechanism. The proposed method applies L2 clipping to bound collaborator updates, computes similarity-based aggregation weights to mitigate the effects of non-IID data distributions, and injects calibrated Gaussian noise at the central server, providing per-round privacy guarantees under the assumed sensitivity bound. The framework is implemented using Intel's OpenFL platform and evaluated on the FeTS 2022 dataset consisting of 1251 multi-modal MRI scans for brain tumor segmentation. Experimental results demonstrate that DP-SimAgg maintains competitive segmentation performance while providing privacy protection. Under a strict per-round privacy budget (epsilon = 1, cumulative epsilon_total = 20 over 20 rounds), the method achieves Dice scores of 0.6357, 0.5305, and 0.5274 for the enhancing tumor (ET), tumor core (TC), and whole tumor (WT) regions, respectively. With a more relaxed per-round budget (epsilon = 10, cumulative epsilon_total = 200), performance approaches that of the non-private baseline while incorporating a central Gaussian mechanism with per-round (epsilon, delta)-DP accounting under the assumed sensitivity bound. These results highlight the potential of DP-SimAgg for enabling privacy-preserving collaborative learning in medical imaging applications.
Muhammad Irfan Khan, Eero Lehtonen, Joni Obradovic +4
Deep learning models for neuroimaging have largely been developed for individual tasks, limiting knowledge transfer across applications. Here we introduce GenFAR, a modular deep learning framework that learns general, clinically informed features from brain MRIs. We trained this modular architecture on 49,246 individuals across 11 cohorts, using 17 diverse classification and regression tasks spanning cognition, clinical, diagnosis, demographics, and biomarkers. This yields aggregated, focused feature sets that capture rich, clinically- and biologically-relevant brain representations. We developed a sequential learning approach where tasks progressively build on previously learned representations. Through an analysis of 5,000 task sequences, we identified an optimal sequence length of six tasks and introduced a Donor Score metric to quantify each task's contribution to downstream performance. This analysis revealed five consistently strong donor tasks (Age, AD/MCI, MMSE, Hypertension, Hyperlipidemia) that formed the base of our sequential model. We demonstrated the utility of our learned representation, in various tasks beyond those included in the training set, to serve as the foundation for specialized secondary predictors. We further showed that using the learned feature representation can substantially increase the sample efficiency of secondary deep learning training tasks and models, as well as improve their accuracy.