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Test-retest reliability of FreeSurfer measures of neurodegeneration.

Overview

Authors: Henry Rusinek1,2, Louisa Bokacheva3, Haiyun Chen3, Arjun Masurkar3, Ricardo Osorio2, Rebecca Betensky4, Alok Vedvyas3, Joshua Chodosh5, Yongzhao Shao6, Timothy Shepherd1, Karyn Marsh3, Thomas Wisniewski3
  1. Department of Radiology and Psychiatry, NYU Grossman School of Medicine, 660 First Ave, New York, NY 10016, USA
  2. Department of Psychiatry, NYU Grossman School of Medicine, 145 East 32nd Street, New York, NY 10016, USA
  3. Department of Neurology, NYU Grossman School of Medicine, 145 East 32nd Street, New York, NY 10016, USA
  4. Department of Biostatistics, NYU School of Global Public Health, 708 Broadway, New York, NY 10003, USA
  5. Department of Medicine, NYU Grossman School of Medicine, 550 First Ave, New York, NY 10016, USA
  6. Department of Population Health, NYU Grossman School of Medicine, 550 First Ave, New York, NY 10016, USA
Institutions: New York University (United States); NYU Langone Health (United States)
Journal: NeuroImage, volume 333, article 121920
Dates: published online 9 April 2026; in print June 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.neuroimage.2026.121920 · PMID 41966233 · PMCID PMC13293555 · OpenAlex W7152454045
Open access: gold, a free copy (OpenAlex)
Status: code on request
Categories: structural MRI / diffusion (modality), human (organism), Alzheimer's / dementia (population), methods / tools (subfield)
Methods: Statistics, fMRI & imaging, Preprocessing
MeSH: Alzheimer Disease*, Brain*, Magnetic Resonance Imaging*, Aged, Aged, 80 and over, Aging, Female, Humans, Male, Reproducibility of Results (* major topic)
Topic: Parkinson's Disease Mechanisms and Treatments (Neurology, Medicine), according to OpenAlex
Funding: National Institute on Aging (P30AG066512); NINDS NIH HHS (U24 NS141774); NIA NIH HHS (P30 AG066512)
Citations: not cited yet (Europe PMC); 37 references in the paper

Abstract

Reliable structural brain measurements are essential for studying neurodegeneration and for designing adequately powered aging and Alzheimer’s disease (AD) research. We evaluated the test–retest reliability of FreeSurfer 7.1 morphometric measures in 100 older adults (mean age 73.5 years) ranging from cognitively unimpaired to dementia. Each participant underwent two T1-weighted 3T MRI scans on the same scanner within a short interval (mean 5.5 weeks), minimizing biological change. Segmentation was performed in both standard cross-sectional and longitudinal FreeSurfer modes, focusing on AD-relevant volumes of entorhinal cortex, hippocampus, lateral ventricles, choroid plexus, and the AD cortical thickness signature. Reliability was quantified using absolute and root-mean-square test–retest differences, standard deviation of differences, and intraclass correlation coefficients. Longitudinal processing improved precision by 15–50% across most measures compared with cross-sectional processing, with the largest gain observed for entorhinal thickness. Larger, anatomically well-defined regions (e.g., hippocampus, AD signature) demonstrated higher reliability than small structures or those with complex geometry (e.g., entorhinal cortex, choroid plexus). Image quality, indexed by the Euler characteristic, was the only factor significantly associated with measurement variability; reliability was unrelated to age, sex, cognitive status, inter-scan interval, or amyloid/tau PET burden. Power analyses indicated that detecting a 1% within-individual change requires sample sizes ranging from 36 (AD signature) to >300 (entorhinal cortex). We observed low reliability of choroid plexus volumetry by FreeSurfer 7. These results provide practical benchmarks for expected FreeSurfer measurement variability in older adults. They highlight the advantages of longitudinal processing and rigorous quality control for research on brain aging and AD.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

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Data

No dataset and no data link were found in the paper.

Data and code availability statement

The data used in this study contain sensitive human participant information and cannot be made publicly available due to institutional ethical restrictions and participant privacy protections. De-identified data may be made available to qualified researchers upon reasonable request and completion of a data use agreement.

Analysis code used in this study is available from the corresponding author upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 29 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 12 authors, 10 MeSH terms, 3 funders, 35 references.

Cite

This paper

Rusinek, H., Bokacheva, L., Chen, H., Masurkar, A., Osorio, R., Betensky, R., Vedvyas, A., Chodosh, J., Shao, Y., Shepherd, T., Marsh, K., & Wisniewski, T. (2026). Test-retest reliability of FreeSurfer measures of neurodegeneration. NeuroImage, 333, 121920. https://doi.org/10.1016/j.neuroimage.2026.121920

BibTeX

@article{rusinek2026test,
author = {Rusinek, Henry and Bokacheva, Louisa and Chen, Haiyun and Masurkar, Arjun and Osorio, Ricardo and Betensky, Rebecca and Vedvyas, Alok and Chodosh, Joshua and Shao, Yongzhao and Shepherd, Timothy and Marsh, Karyn and Wisniewski, Thomas},
title = {{Test-retest reliability of FreeSurfer measures of neurodegeneration}},
journal = {NeuroImage},
year = {2026},
month = apr,
volume = {333},
pages = {121920},
publisher = {Elsevier BV},
issn = {1053-8119},
doi = {10.1016/j.neuroimage.2026.121920},
url = {https://doi.org/10.1016/j.neuroimage.2026.121920},
pmid = {41966233},
pmcid = {PMC13293555}
}

RIS

TY - JOUR
AU - Rusinek, Henry
AU - Bokacheva, Louisa
AU - Chen, Haiyun
AU - Masurkar, Arjun
AU - Osorio, Ricardo
AU - Betensky, Rebecca
AU - Vedvyas, Alok
AU - Chodosh, Joshua
AU - Shao, Yongzhao
AU - Shepherd, Timothy
AU - Marsh, Karyn
AU - Wisniewski, Thomas
TI - Test-retest reliability of FreeSurfer measures of neurodegeneration
T2 - NeuroImage
J2 - Neuroimage
PY - 2026
DA - 2026/04/09
VL - 333
SP - 121920
SN - 1053-8119
PB - Elsevier BV
DO - 10.1016/j.neuroimage.2026.121920
UR - https://doi.org/10.1016/j.neuroimage.2026.121920
LA - en
ER -

CSL-JSON

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