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

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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Publication Details

Journal
Scientific Data
Published
2025-05-06
DOI
https://doi.org/10.1038/s41597-025-05028-2
Citations
11
Primary Topic
Advanced Neuroimaging Techniques and Applications
Type
article
Field-Weighted Citation Impact
14.96

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article

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

John Blangero, Katie L. McMahon, Shayan Javid, Sarah Elizabeth Medland et al.
11 citations
Scientific Data
Advanced Neuroimaging Techniques and Applications
14.96
article

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

John Blangero, Katie L. McMahon, Shayan Javid, Sarah Elizabeth Medland, Neda Jahanshad, Douglas E. Williamson, Peter Kochunov, Greig I. de Zubicaray, Margaret J. Wright, Asta Kristine Haberg, Lachlan T. Strike, Alyssa H. Zhu, Amanda Rodrigue, Julio E. Villalón‐Reina, David C. Glahn, Talia M. Nir, Paul M. Thompson
article en
11 citations

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 ).

Scientific DataVol. 12(1)
Boston Children's Hospital (US), Harvard University (US), Viterbo University (US), Queensland University of Technology (AU), The University of Queensland (AU), Duke University (US), Norwegian University of Science and Technology (NO), QIMR Berghofer Medical Research Institute (AU), Keck Hospital of USC (US), The University of Texas Rio Grande Valley (US), St Olav's University Hospital (NO), National Imaging Facility (AU), Durham VA Health Care System (US), Institute for Community Living (US), Imaging Center (US), Hartford Financial Services (United States), The University of Texas Health Science Center at Houston (US)
Alzheimer's Association, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Sanofi, Biogen, Teva Pharmaceutical Industries, Celgene, Wellcome Trust, Jazz Pharmaceuticals, Chongqing Postdoctoral Science Foundation, Neurocrine Biosciences, Verily Life Sciences, Voyager Therapeutics, Cancer Research UK, British Heart Foundation, National Natural Science Foundation of China, China Postdoctoral Science Foundation, Northwest Regional Development Agency, Natural Science Foundation of Chongqing, Southwest University, Fok Ying Tung Education Foundation, Servier, H. Lundbeck A/S, Sun Pharma, National Institutes of Health, Genentech, Allergan, Medical Research Council, National Health and Medical Research Council, Fundamental Research Funds for the Central Universities, National Institute of Mental Health, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Openalex Percentile: Top 1%
Advanced Neuroimaging Techniques and Applications
14.96
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