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Published on: November 8, 2012
Comparing Harmonization Approaches for Protocol-Related Variability in Multisite Diffusion MRI Data
Kenny Liou1, Sophia I Thomopoulos1, Julio E Villalon Reina1
1Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
Biorxiv : the Preprint Server for Biology
|July 17, 2026
Summary
Harmonizing diffusion MRI data across multiple protocols in Alzheimer's Disease Neuroimaging Initiative (ADNI) studies is crucial. Three methods effectively reduced variability while preserving key associations with cognitive decline and disease biomarkers.
Area of Science:
- Neuroimaging
- Radiology
- Neurology
Background:
- Diffusion MRI (dMRI) reveals white matter changes in Alzheimer's Disease (AD).
- Multisite dMRI data present challenges due to varying acquisition protocols.
- The Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset utilizes over 10 dMRI protocols.
Purpose of the Study:
- To compare three data harmonization methods for dMRI data.
- To assess the reduction of protocol-related variability in diffusion tensor imaging metrics.
- To evaluate the preservation of associations with cognitive impairment and AD biomarkers.
Main Methods:
- Comparison of three harmonization techniques: mixed-effects models, ComBat-GAM, and eHarmonize.
- Analysis of diffusion tensor imaging fractional anisotropy (FA) and mean diffusivity (MD) data.
- Evaluation in 1,086 ADNI3/4 participants with cognitive and PET imaging data.
Main Results:
- All three methods successfully aligned FA and MD distributions across different dMRI protocols.
- Associations between dMRI metrics and cognitive impairment were consistent across harmonization approaches.
- Associations with amyloid-beta and tau PET burden showed more variability.
Conclusions:
- Multiple harmonization strategies effectively address protocol-related variability in multisite dMRI data.
- These methods preserve crucial associations between dMRI metrics and cognitive status in AD.
- Careful consideration of harmonization is essential for robust analysis of pooled dMRI datasets.

