Abstract:Accurate and reproducible brain morphometry from structural MRI is critical for monitoring neuroanatomical changes across time and across imaging domains. Although deep learning has accelerated segmentation workflows, scanner-induced variability and reproducibility limitations remain-especially in longitudinal and multi-site settings. In this study, we benchmark two modern segmentation pipelines, FastSurfer and SynthSeg, both integrated into FreeSurfer, one of the most widely adopted tools in neuroimaging. Using two complementary datasets - a 17-year longitudinal cohort (SIMON) and a 9-site test-retest cohort (SRPBS)-we quantify inter-scan segmentation variability using Dice coefficient, Surface Dice, Hausdorff Distance (HD95), and Mean Absolute Percentage Error (MAPE). Our results reveal up to 7-8% volume variation in small subcortical structures such as the amygdala and ventral diencephalon, even under controlled test-retest conditions. This raises a key question: is it feasible to detect subtle longitudinal changes on the order of 5-10% in pea-sized brain regions, given the magnitude of domain-induced morphometric noise? We further analyze the effects of registration templates and interpolation modes, and propose surface-based quality filtering to improve segmentation reliability. This study provides a reproducible benchmark for morphometric reproducibility and emphasizes the need for harmonization strategies in real-world neuroimaging studies. Code and figures: https://github.com/kondratevakate/brain-mri-segmentation