Leveraging Segmentation Variability to Improve Brain Age Prediction

Abstract

Analytical variability in neuroimaging pipelines contributes to concerns about reproducibility in the field. In structural MRI, different segmentation tools produce discrepant morphometric estimates that may influence downstream analyses, such as predictive modeling. We tested whether integrating several segmentation pipelines improves brain age prediction, and characterized the spatial and demographic structure of pipeline differences across several datasets. T1-weighted scans from five open-access datasets were processed with four widely-used structural segmentation pipelines. Brain age models were trained using single-pipeline features and compared with multi-pipeline aggregation strategies. Inter-pipeline variability was assessed across shared subcortical structures and examined in relation to age and sex. Integrating features across distinct segmentation frameworks improved predictive performance relative to individual pipelines, whereas aggregation within closely related software versions provided limited benefit. Variability was spatially structured and volumetric measures were often systematically associated with age and sex. These results suggest that segmentation differences reflect structured, demographically sensitive variation rather than random noise, and that multi-pipeline feature integration can enhance robustness in neuroimaging-based prediction.