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

Area of Science:

• Neuroscience
• Radiology
• Biostatistics

Background:

• White matter (WM) microstructure undergoes maturation and decline throughout human life.
• Understanding these age-related changes is crucial for diagnosing neurodegenerative diseases.

Purpose of the Study:

• To establish normative lifespan reference curves for global and regional WM microstructure.
• To assess the impact of the ApoE4 gene on WM integrity across the lifespan.

Main Methods:

• Harmonized diffusion MRI (dMRI) data from 40,898 subjects (ages 3-95) using three methods.
• Applied ComBat-GAM harmonization to regional diffusion tensor imaging (DTI)-derived fractional anisotropy (FA) via the ENIGMA-DTI pipeline.
• Validated FA reference curves with test-retest data and analyzed ApoE4 effects.

Main Results:

• ComBat-GAM harmonization yielded WM maturation trajectories consistent with known peaks.
• Lifespan FA reference curves were successfully generated and validated.
• Significant associations between ApoE4 and WM FA were observed across the lifespan, including in healthy individuals, with regional age-by-genotype interactions.

Conclusions:

• Developed publicly available lifespan reference curves for WM microstructure (eHarmonize).
• The ApoE4 risk factor for dementia impacts WM integrity throughout life, even in healthy individuals.
• These reference curves provide a valuable tool for studying WM changes and genetic influences across the lifespan.