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Free water elimination tractometry for aging brains.

Kelly Chang¹, Luke Burke², Nina LaPiana³

¹Department of Psychology, University of Washington, Seattle, WA, United States.

Imaging Neuroscience (Cambridge, Mass.)

|November 13, 2025

Summary

Free water elimination (FWE) and multi-shell modeling improve diffusion MRI tractometry reliability in aging brains. These methods enhance accuracy and yield, even with single-shell data, highlighting the need to account for free water in older adults.

Keywords:

aging diffusion imaging free water elimination tractography tractometry

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Area of Science:

Neuroimaging
Biomedical Engineering
Gerontology

Background:

Diffusion MRI tractometry is crucial for studying brain connections in aging.
Increased white matter free water in aging brains can reduce tractometry reliability.
Existing methods may not fully account for age-related changes in white matter microstructure.

Purpose of the Study:

To evaluate the impact of free water elimination (FWE) and multi-shell multi-tissue (MSMT) modeling on tractometry reliability and accuracy in older adults.
To assess the generalizability of findings to single-shell diffusion MRI datasets.
To investigate the relationship between tractometry metrics and white matter hyperintensity burden.

Main Methods:

Applied FWE and MSMT modeling to diffusion MRI data from 396 older adults (65-103 years).
Assessed tractometry reliability using split-half comparisons across the analysis pipeline.
Correlated tractometry outcomes with Fazekas scores for white matter hyperintensity burden.
Simulated single-shell data from multi-shell datasets to test generalizability.

Main Results:

Both FWE and MSMT modeling significantly improved tractometry reliability and accuracy.
FWE enhanced tractography yield and coverage in areas with leukoaraiosis.
Tractometry findings were strongly predictive of Fazekas scores, indicating global white matter changes.
Results generalized to single-shell data, suggesting applicability to diverse datasets.

Conclusions:

Accounting for free water is essential for reliable and accurate tractometry in aging brains.
FWE and MSMT modeling offer robust solutions for analyzing white matter integrity in older populations.
The findings underscore the impact of white matter hyperintensities on overall brain connectivity.