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Fed-ComBat: A Generalized Federated Framework for Batch Effect Harmonization in Collaborative Studies

Silva, S., Lorenzi, M., Altmann, A., Oxtoby, N.

biorxiv logopreprintMay 14 2025
In neuroimaging research, the utilization of multi-centric analyses is crucial for obtaining sufficient sample sizes and representative clinical populations. Data harmonization techniques are typically part of the pipeline in multi-centric studies to address systematic biases and ensure the comparability of the data. However, most multi-centric studies require centralized data, which may result in exposing individual patient information. This poses a significant challenge in data governance, leading to the implementation of regulations such as the GDPR and the CCPA, which attempt to address these concerns but also hinder data access for researchers. Federated learning offers a privacy-preserving alternative approach in machine learning, enabling models to be collaboratively trained on decentralized data without the need for data centralization or sharing. In this paper, we present Fed-ComBat, a federated framework for batch effect harmonization on decentralized data. Fed-ComBat extends existing centralized linear methods, such as ComBat and distributed as d-ComBat, and nonlinear approaches like ComBat-GAM in accounting for potentially nonlinear and multivariate covariate effects. By doing so, Fed-ComBat enables the preservation of nonlinear covariate effects without requiring centralization of data and without prior knowledge of which variables should be considered nonlinear or their interactions, differentiating it from ComBat-GAM. We assessed Fed-ComBat and existing approaches on simulated data and multiple cohorts comprising healthy controls (CN) and subjects with various disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), and autism spectrum disorder (ASD). The results of our study show that Fed-ComBat performs better than centralized ComBat when dealing with nonlinear effects and is on par with centralized methods like ComBat-GAM. Through experiments using synthetic data, Fed-ComBat demonstrates a superior ability to reconstruct the target unbiased function, achieving a 35% improvement (RMSE=0.5952) compared to d-ComBat (RMSE=0.9162) and a 12% improvement compared to our proposal to federate ComBat-GAM, d-ComBat-GAM (RMSE=0.6751). Additionally, Fed-ComBat achieves comparable results to centralized methods like ComBat-GAM for MRI-derived phenotypes without requiring prior knowledge of potential nonlinearities.

AmygdalaGo-BOLT: an open and reliable AI tool to trace boundaries of human amygdala

Zhou, Q., Dong, B., Gao, P., Jintao, W., Xiao, J., Wang, W., Liang, P., Lin, D., Zuo, X.-N., He, H.

biorxiv logopreprintMay 13 2025
Each year, thousands of brain MRI scans are collected to study structural development in children and adolescents. However, the amygdala, a particularly small and complex structure, remains difficult to segment reliably, especially in developing populations where its volume is even smaller. To address this challenge, we developed AmygdalaGo-BOLT, a boundary-aware deep learning model tailored for human amygdala segmentation. It was trained and validated using 854 manually labeled scans from pediatric datasets, with independent samples used to ensure performance generalizability. The model integrates multiscale image features, spatial priors, and self-attention mechanisms within a compact encoder-decoder architecture to enhance boundary detection. Validation across multiple imaging centers and age groups shows that AmygdalaGo-BOLT closely matches expert manual labels, improves processing efficiency, and outperforms existing tools in accuracy. This enables robust and scalable analysis of amygdala morphology in developmental neuroimaging studies where manual tracing is impractical. To support open and reproducible science, we publicly release both the labeled datasets and the full source code.
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