Lifespan reference curves for harmonizing multi-site regional brain white matter metrics from diffusion MRI

Abstract Age-related white matter (WM) microstructure maturation and decline occur throughout the human lifespan, complementing the process of gray matter development and degeneration. Here, we create normative lifespan reference curves for global and regional WM microstructure by harmonizing diffus...

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Main Authors: Alyssa H. Zhu, Talia M. Nir, Shayan Javid, Julio E. Villalón-Reina, Amanda L. Rodrigue, Lachlan T. Strike, Greig I. de Zubicaray, Katie L. McMahon, Margaret J. Wright, Sarah E. Medland, John Blangero, David C. Glahn, Peter Kochunov, Douglas E. Williamson, Asta K. Håberg, Paul M. Thompson, Neda Jahanshad
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Data
Online Access:https://doi.org/10.1038/s41597-025-05028-2
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author Alyssa H. Zhu
Talia M. Nir
Shayan Javid
Julio E. Villalón-Reina
Amanda L. Rodrigue
Lachlan T. Strike
Greig I. de Zubicaray
Katie L. McMahon
Margaret J. Wright
Sarah E. Medland
John Blangero
David C. Glahn
Peter Kochunov
Douglas E. Williamson
Asta K. Håberg
Paul M. Thompson
Neda Jahanshad
author_facet Alyssa H. Zhu
Talia M. Nir
Shayan Javid
Julio E. Villalón-Reina
Amanda L. Rodrigue
Lachlan T. Strike
Greig I. de Zubicaray
Katie L. McMahon
Margaret J. Wright
Sarah E. Medland
John Blangero
David C. Glahn
Peter Kochunov
Douglas E. Williamson
Asta K. Håberg
Paul M. Thompson
Neda Jahanshad
author_sort Alyssa H. Zhu
collection DOAJ
description Abstract Age-related white matter (WM) microstructure maturation and decline occur throughout the human lifespan, complementing the process of gray matter development and degeneration. Here, we create normative lifespan reference curves for global and regional WM microstructure by harmonizing diffusion MRI (dMRI)-derived data from ten public datasets (N = 40,898 subjects; age: 3–95 years; 47.6% male). We tested three harmonization methods on regional diffusion tensor imaging (DTI) based fractional anisotropy (FA), a metric of WM microstructure, extracted using the ENIGMA-DTI pipeline. ComBat-GAM harmonization provided multi-study trajectories most consistent with known WM maturation peaks. Lifespan FA reference curves were validated with test-retest data and used to assess the effect of the ApoE4 risk factor for dementia in WM across the lifespan. We found significant associations between ApoE4 and FA in WM regions associated with neurodegenerative disease even in healthy individuals across the lifespan, with regional age-by-genotype interactions. Our lifespan reference curves and tools to harmonize new dMRI data to the curves are publicly available as eHarmonize ( https://github.com/ahzhu/eharmonize ).
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spelling doaj-art-42f852eee65744e1b35c4eb5a1c97d832025-08-20T01:49:39ZengNature PortfolioScientific Data2052-44632025-05-0112111810.1038/s41597-025-05028-2Lifespan reference curves for harmonizing multi-site regional brain white matter metrics from diffusion MRIAlyssa H. Zhu0Talia M. Nir1Shayan Javid2Julio E. Villalón-Reina3Amanda L. Rodrigue4Lachlan T. Strike5Greig I. de Zubicaray6Katie L. McMahon7Margaret J. Wright8Sarah E. Medland9John Blangero10David C. Glahn11Peter Kochunov12Douglas E. Williamson13Asta K. Håberg14Paul M. Thompson15Neda Jahanshad16Imaging Genetics Center, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USCImaging Genetics Center, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USCImaging Genetics Center, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USCImaging Genetics Center, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USCDepartment of Psychiatry and Behavioral Science, Boston Children’s Hospital, Harvard Medical SchoolQIMR Berghofer Medical Research InstituteQueensland University of TechnologyQueensland University of TechnologyQueensland Brain Institute, University of QueenslandQIMR Berghofer Medical Research InstituteDepartment of Human Genetics, University of Texas Rio Grande ValleyDepartment of Psychiatry and Behavioral Science, Boston Children’s Hospital, Harvard Medical SchoolFaillace Department of Psychiatry and Behavioral Sciences at McGovern Medical School, The University of Texas Health Science Center at HoustonDepartment of Psychiatry and Behavioral Sciences, Duke University School of MedicineDepartment of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU)Imaging Genetics Center, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USCImaging Genetics Center, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USCAbstract Age-related white matter (WM) microstructure maturation and decline occur throughout the human lifespan, complementing the process of gray matter development and degeneration. Here, we create normative lifespan reference curves for global and regional WM microstructure by harmonizing diffusion MRI (dMRI)-derived data from ten public datasets (N = 40,898 subjects; age: 3–95 years; 47.6% male). We tested three harmonization methods on regional diffusion tensor imaging (DTI) based fractional anisotropy (FA), a metric of WM microstructure, extracted using the ENIGMA-DTI pipeline. ComBat-GAM harmonization provided multi-study trajectories most consistent with known WM maturation peaks. Lifespan FA reference curves were validated with test-retest data and used to assess the effect of the ApoE4 risk factor for dementia in WM across the lifespan. We found significant associations between ApoE4 and FA in WM regions associated with neurodegenerative disease even in healthy individuals across the lifespan, with regional age-by-genotype interactions. Our lifespan reference curves and tools to harmonize new dMRI data to the curves are publicly available as eHarmonize ( https://github.com/ahzhu/eharmonize ).https://doi.org/10.1038/s41597-025-05028-2
spellingShingle Alyssa H. Zhu
Talia M. Nir
Shayan Javid
Julio E. Villalón-Reina
Amanda L. Rodrigue
Lachlan T. Strike
Greig I. de Zubicaray
Katie L. McMahon
Margaret J. Wright
Sarah E. Medland
John Blangero
David C. Glahn
Peter Kochunov
Douglas E. Williamson
Asta K. Håberg
Paul M. Thompson
Neda Jahanshad
Lifespan reference curves for harmonizing multi-site regional brain white matter metrics from diffusion MRI
Scientific Data
title Lifespan reference curves for harmonizing multi-site regional brain white matter metrics from diffusion MRI
title_full Lifespan reference curves for harmonizing multi-site regional brain white matter metrics from diffusion MRI
title_fullStr Lifespan reference curves for harmonizing multi-site regional brain white matter metrics from diffusion MRI
title_full_unstemmed Lifespan reference curves for harmonizing multi-site regional brain white matter metrics from diffusion MRI
title_short Lifespan reference curves for harmonizing multi-site regional brain white matter metrics from diffusion MRI
title_sort lifespan reference curves for harmonizing multi site regional brain white matter metrics from diffusion mri
url https://doi.org/10.1038/s41597-025-05028-2
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