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Challenges and best practices when using ComBAT to harmonize diffusion MRI data.

Publication ,  Journal Article
Jodoin, P-M; Edde, M; Girard, G; Dumais, F; Theaud, G; Dumont, M; Houde, J-C; David, Y; Descoteaux, M; Alzheimer’s Disease Neuroimaging Initiative
Published in: Sci Rep
November 24, 2025

Over the years, ComBAT has become the standard method for harmonizing MRI-derived measurements, with its ability to compensate for site-related additive and multiplicative biases while preserving biological variability. However, ComBAT relies on a set of assumptions that, when violated, can result in flawed harmonization. In this paper, we thoroughly review ComBAT's mathematical foundation, outlining these assumptions, and exploring their implications for the demographic composition necessary for optimal results. Through a series of experiments involving a slightly modified version of ComBAT called Pairwise-ComBAT tailored for normative modeling applications, we assess the impact of various population characteristics, including population size, age distribution, the absence of certain covariates, and the magnitude of additive and multiplicative factors. Based on these experiments, we present five essential recommendations that should be carefully considered to enhance consistency and supporting reproducibility, two essential factors for open science, collaborative research, and real-life clinical deployment.

Duke Scholars

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

November 24, 2025

Volume

15

Issue

1

Start / End Page

41508

Location

England

Related Subject Headings

  • Reproducibility of Results
  • Image Processing, Computer-Assisted
  • Humans
  • Diffusion Magnetic Resonance Imaging
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Jodoin, P.-M., Edde, M., Girard, G., Dumais, F., Theaud, G., Dumont, M., … Alzheimer’s Disease Neuroimaging Initiative. (2025). Challenges and best practices when using ComBAT to harmonize diffusion MRI data. Sci Rep, 15(1), 41508. https://doi.org/10.1038/s41598-025-25400-x
Jodoin, Pierre-Marc, Manon Edde, Gabriel Girard, Felix Dumais, Guillaume Theaud, Matthieu Dumont, Jean-Christophe Houde, Yoan David, Maxime Descoteaux, and Alzheimer’s Disease Neuroimaging Initiative. “Challenges and best practices when using ComBAT to harmonize diffusion MRI data.Sci Rep 15, no. 1 (November 24, 2025): 41508. https://doi.org/10.1038/s41598-025-25400-x.
Jodoin P-M, Edde M, Girard G, Dumais F, Theaud G, Dumont M, et al. Challenges and best practices when using ComBAT to harmonize diffusion MRI data. Sci Rep. 2025 Nov 24;15(1):41508.
Jodoin, Pierre-Marc, et al. “Challenges and best practices when using ComBAT to harmonize diffusion MRI data.Sci Rep, vol. 15, no. 1, Nov. 2025, p. 41508. Pubmed, doi:10.1038/s41598-025-25400-x.
Jodoin P-M, Edde M, Girard G, Dumais F, Theaud G, Dumont M, Houde J-C, David Y, Descoteaux M, Alzheimer’s Disease Neuroimaging Initiative. Challenges and best practices when using ComBAT to harmonize diffusion MRI data. Sci Rep. 2025 Nov 24;15(1):41508.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

November 24, 2025

Volume

15

Issue

1

Start / End Page

41508

Location

England

Related Subject Headings

  • Reproducibility of Results
  • Image Processing, Computer-Assisted
  • Humans
  • Diffusion Magnetic Resonance Imaging