Agreement and longitudinal repeatability of established brain volumetry pipelines across healthy controls, multiple sclerosis, and Alzheimer's disease
6 affiliations
- 1Roche Pharma Research and Early Development, Neuroscience and Rare Diseases Biomarkers
- 2Faculty of Mathematics, Natural Sciences and Information Technologies, University of Primorska
- 3Sherbrooke Connectivity Imaging Lab (SCIL), University of Sherbrooke
- 4Division of Neurology, Department of Medicine, University of Sherbrooke (Université de Sherbrooke)
- 5Research Centre of the Sherbrooke University Hospital Centre (Centre de recherche du Centre hospitalier universitaire de Sherbrooke)
- 6Division of Neurology, Department of Medicine, Centre Hospitalier Universitaire de Sherbrooke
Abstract
Introduction: Brain volume estimates are increasingly used as longitudinal endpoints in neuroimaging studies and clinical trials, but outputs from different segmentation pipelines may not be interchangeable. In this study, we performed a version-specific comparison of six established brain segmentation pipelines across healthy controls (HC; n = 20), people with multiple sclerosis (MS; n = 19), and people with Alzheimer's disease (AD; n = 50).
Methods: FreeSurfer v6, FreeSurfer v7.2, SAMSEG, FastSurfer v1, SIENAX/SIENA-XL, and CAT12 were evaluated. The primary aims were to quantify systematic offsets and inter-pipeline agreement in normalized baseline volume estimates, assess within-pipeline repeatability and longitudinal change-from-baseline concordance, and determine whether longitudinal processing reduced variability relative to cross-sectional processing. Gray matter, white matter, hippocampus, and thalamus were selected and normalized to intracranial volume. Agreement was assessed using intraclass correlation coefficients, while longitudinal change was evaluated using mixed-effects models and repeatability metrics.
Results: Baseline volume estimates differed significantly across pipelines in 11 of 12 cohort-by-tissue comparisons (FDR-adjusted p < 0.001), with the largest pipeline-dependent offsets observed for grey matter, hippocampus, and thalamus. Inter-pipeline agreement was generally strong for white matter and lower for gray matter and subcortical structures (hippocampus and thalamus), particularly in pathological cohorts. Change-from-baseline models showed no significant Pipeline × Timepoint interactions after FDR correction, indicating broadly parallel longitudinal trajectories across pipelines after baseline normalization. However, significant pipeline main effects persisted in selected tissues, especially in AD and subcortical regions, indicating residual differences in the magnitude of estimated change. Longitudinal processing reduced within-subject variability in selected settings, particularly for FreeSurfer-derived hippocampal and thalamic estimates, but did not uniformly improve stability across all pipelines or tissues.
Discussion: Together, these findings show that systematic offset, absolute agreement, longitudinal change magnitude, and short-interval repeatability represent distinct properties of volumetric pipelines and vary by tissue, cohort, and processing mode. Longitudinal processing reduced variability but not uniformly, highlighting pipeline- and tissue-dependent differences relevant to the interpretation of longitudinal volumetric measurements.
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BibTeX
@article{sisic2026agreement,
title = {{Agreement and longitudinal repeatability of established brain volumetry pipelines across healthy controls, multiple sclerosis, and Alzheimer's disease}},
author = {Nedim Šišić and Muhamed Barakovic and Manon Edde and Antoine Théberge and Ann-Marie Beaudoin and Moussa Dumbia and Emmanuelle Lapointe and Maxime Descoteaux and Stefano Magon and Susanna Gobbi},
journal = {Frontiers in Neuroscience},
year = {2026},
month = oct,
doi = {10.3389/fnins.2026.1917471},
url = {https://www.frontiersin.org/articles/10.3389/fnins.2026.1917471/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Agreement and longitudinal repeatability of established brain volumetry pipelines across healthy controls, multiple sclerosis, and Alzheimer's disease
AU - Nedim Šišić
AU - Muhamed Barakovic
AU - Manon Edde
AU - Antoine Théberge
AU - Ann-Marie Beaudoin
AU - Moussa Dumbia
AU - Emmanuelle Lapointe
AU - Maxime Descoteaux
AU - Stefano Magon
AU - Susanna Gobbi
PY - 2026
DA - 2026/10/16
JO - Frontiers in Neuroscience
DO - 10.3389/fnins.2026.1917471
UR - https://www.frontiersin.org/articles/10.3389/fnins.2026.1917471/full
AB - Introduction: Brain volume estimates are increasingly used as longitudinal endpoints in neuroimaging studies and clinical trials, but outputs from different segmentation pipelines may not be interchangeable. In this study, we performed a version-specific comparison of six established brain segmentation pipelines across healthy controls (HC; n = 20), people with multiple sclerosis (MS; n = 19), and people with Alzheimer's disease (AD; n = 50). Methods: FreeSurfer v6, FreeSurfer v7.2, SAMSEG, FastSurfer v1, SIENAX/SIENA-XL, and CAT12 were evaluated. The primary aims were to quantify systematic offsets and inter-pipeline agreement in normalized baseline volume estimates, assess within-pipeline repeatability and longitudinal change-from-baseline concordance, and determine whether longitudinal processing reduced variability relative to cross-sectional processing. Gray matter, white matter, hippocampus, and thalamus were selected and normalized to intracranial volume. Agreement was assessed using intraclass correlation coefficients, while longitudinal change was evaluated using mixed-effects models and repeatability metrics. Results: Baseline volume estimates differed significantly across pipelines in 11 of 12 cohort-by-tissue comparisons (FDR-adjusted p < 0.001), with the largest pipeline-dependent offsets observed for grey matter, hippocampus, and thalamus. Inter-pipeline agreement was generally strong for white matter and lower for gray matter and subcortical structures (hippocampus and thalamus), particularly in pathological cohorts. Change-from-baseline models showed no significant Pipeline × Timepoint interactions after FDR correction, indicating broadly parallel longitudinal trajectories across pipelines after baseline normalization. However, significant pipeline main effects persisted in selected tissues, especially in AD and subcortical regions, indicating residual differences in the magnitude of estimated change. Longitudinal processing reduced within-subject variability in selected settings, particularly for FreeSurfer-derived hippocampal and thalamic estimates, but did not uniformly improve stability across all pipelines or tissues. Discussion: Together, these findings show that systematic offset, absolute agreement, longitudinal change magnitude, and short-interval repeatability represent distinct properties of volumetric pipelines and vary by tissue, cohort, and processing mode. Longitudinal processing reduced variability but not uniformly, highlighting pipeline- and tissue-dependent differences relevant to the interpretation of longitudinal volumetric measurements.
SN - 1662-453X
SN - 1662-4548
ER -