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Co-analysis of Brain Structure and Function using fMRI and Diffusion-weighted Imaging

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

Alyssa H Zhu^1,2, Talia M Nir¹, Shayan Javid^1,2

¹Imaging Genetics Center, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA.

Scientific Data

|May 6, 2025

Summary

Researchers created normative white matter (WM) microstructure reference curves across the lifespan using harmonized diffusion MRI data. The ApoE4 gene variant showed associations with WM integrity, even in healthy individuals.

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Area of Science:

Neuroscience
Radiology
Biostatistics

Background:

White matter (WM) microstructure undergoes maturation and decline throughout human life.
Understanding normative WM development and aging is crucial for identifying neurodegenerative changes.

Purpose of the Study:

To establish normative lifespan reference curves for global and regional WM microstructure.
To harmonize diffusion MRI (dMRI) data across multiple studies for robust analysis.
To investigate the impact of the ApoE4 genotype on WM microstructure across the lifespan.

Main Methods:

Harmonization of dMRI-derived data from 40,898 subjects (ages 3-95) using three methods.
Extraction of regional fractional anisotropy (FA) using the ENIGMA-DTI pipeline.
Validation of lifespan FA reference curves with test-retest data.

Main Results:

ComBat-GAM harmonization yielded trajectories consistent with known WM maturation peaks.
Significant associations between the ApoE4 genotype and WM FA were observed across the lifespan.
Regional age-by-genotype interactions indicated differential effects of ApoE4 on WM integrity.

Conclusions:

Established normative lifespan reference curves for WM microstructure using harmonized dMRI data.
Demonstrated the utility of these curves in assessing genetic risk factors like ApoE4 for neurodegeneration.
Publicly released the eHarmonize tools for dMRI data harmonization.