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Updated: Feb 20, 2026

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Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
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Reproducibility and Reliability of Free-Water-Corrected Diffusion Tensor Imaging of the Brain: Revisited
Tomasz Pieciak1, Guillem París1, Santiago Aja-Fernández1
1Laboratorio de Procesado de Imagen (LPI), ETSI Telecomunicación, Universidad de Valladolid, Valladolid, Spain.
Human Brain Mapping
|February 18, 2026
Summary
Free-water (FW) corrected diffusion tensor imaging (DTI) improves reliability in brain white matter analysis, but results depend on methodology. The combined FW-correction scheme with multiple-shell data offers the most robust DTI measures for clinical applications.
Area of Science:
- Neuroimaging
- Biomedical Engineering
- Medical Physics
Background:
- Diffusion Tensor Imaging (DTI) is essential for mapping white matter structure.
- Free-water (FW) correction in DTI separates hindered diffusion from isotropic fluid signals.
- Assessing FW-corrected DTI reliability is vital for clinical translation.
Purpose of the Study:
- To evaluate the variability, reliability, and separability of FW-corrected DTI measures in healthy human brain white matter.
- To compare three FW-correction techniques across single- and multiple-shell MR acquisitions.
- To identify the optimal FW-correction DTI scheme for clinical applications.
Main Methods:
- Utilized publicly available test-retest DTI databases (intra-scanner, longitudinal, inter-scanner).
- Investigated three FW-correction techniques: variational bi-tensor, region contraction, and spherical means with signal correction.
- Analyzed DTI parameters derived from single- and multiple-shell diffusion-sensitising MR acquisitions.
Main Results:
- FW correction's impact on DTI repeatability is data- and methodology-dependent, not universally applicable to multiple-shell data.
- Single-shell variational FW-correction failed to yield meaningful mean diffusivity (MD) information.
- Combined FW-correction reduced MD variability, especially with multiple-shell derived FW volume fraction (FWVF).
- Fractional anisotropy and axial diffusivity from multiple-shell, combined FW-correction showed highest reliability and repeatability.
- Mean diffusivity and FWVF were the least reliable measures across all FW-correction methods.
Conclusions:
- The choice of FW-correction method and acquisition scheme significantly influences DTI measure reliability.
- Combined FW-correction with multiple-shell data provides the most reliable DTI metrics (FA, AD) for clinical use.
- Mean diffusivity and FWVF are unreliable and should be interpreted cautiously in FW-corrected DTI studies.

