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Updated: May 29, 2026

Co-analysis of Brain Structure and Function using fMRI and Diffusion-weighted Imaging
Published on: November 8, 2012
How and how not to correct for CSF-contamination in diffusion MRI
Claudia Metzler-Baddeley1, Michael J O'Sullivan, Sonya Bells
1Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, and the Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK. Metzler-BaddeleyC@cardiff.ac.uk
Abstract:
Diffusion MRI is used extensively to investigate changes in white matter microstructure related to brain development and pathology. Ageing, however, is also associated with significant white and grey matter loss which in turn can lead to cerebrospinal fluid (CSF) based partial volume artefacts in diffusion MRI metrics. This is especially problematic in regions prone to CSF contamination, such as the fornix and the genu of corpus callosum, structures that pass through or close to the ventricles respectively. The aim of this study was to model the effects of CSF contamination on diffusion MRI metrics, and to evaluate different post-acquisition strategies to correct for CSF-contamination: Controlling for whole brain volume and correcting on a voxel-wise basis using the Free Water Elimination (FWE) approach. Using the fornix as an exemplar of a structure prone to CSF-contamination, corrections were applied to tract-specific and voxel-based [tract based spatial statistics (TBSS)] analyses of empirical DT-MRI data from 39 older adults (53-93 years of age). In addition to significant age-related decreases in whole brain volume and fornix tissue volume fraction, age was also associated with a reduction in mean fractional anisotropy and increase in diffusivity metrics in the fornix. The experimental data agreed with the simulations in that diffusivity metrics (mean diffusivity, axial and radial diffusivity) were more prone to partial volume CSF-contamination errors than fractional anisotropy. After FWE-based voxel-by-voxel partial volume corrections, the significant positive correlations between age and diffusivity metrics, in particular with axial diffusivity, disappeared whereas the correlation with anisotropy remained. In contrast, correcting for whole brain volume had little effect in removing these spurious correlations. Our study highlights the importance of correcting for CSF-contamination partial volume effects in the structures of interest on a voxel-by-voxel basis prior to drawing inferences about underlying changes in white matter structures and have implications for the interpretation of many recent diffusion MRI results in ageing and disease.
Insights
Age-related white matter changes detected by diffusion MRI can be skewed by cerebrospinal fluid (CSF) contamination. Voxel-wise Free Water Elimination (FWE) correction effectively removes these artifacts, unlike whole-brain volume correction, ensuring accurate analysis of aging brain microstructure.
Area of Science:
- Neuroimaging
- Biomedical Engineering
- Gerontology
Background:
- Diffusion MRI is crucial for studying white matter changes in development and disease.
- Aging causes brain volume loss, leading to cerebrospinal fluid (CSF) partial volume artifacts in diffusion MRI metrics.
- These artifacts are particularly problematic in brain regions near ventricles, like the fornix.
Purpose of the Study:
- To model the impact of CSF contamination on diffusion MRI metrics.
- To evaluate post-acquisition correction strategies for CSF contamination: whole-brain volume control versus voxel-wise Free Water Elimination (FWE).
Main Methods:
- Simulated CSF contamination effects on diffusion MRI metrics.
- Applied tract-specific and voxel-based (TBSS) analyses to DT-MRI data from 39 older adults (53-93 years).
- Compared whole-brain volume correction with FWE-based voxel-by-voxel correction using the fornix as a model structure.
Main Results:
- Age-related decreases in whole brain and fornix tissue volume were observed.
- Diffusivity metrics (MD, AD, RD) were more susceptible to CSF contamination than fractional anisotropy (FA).
- FWE correction eliminated spurious age-related correlations with diffusivity metrics, while whole-brain correction had minimal effect.
Conclusions:
- Voxel-by-voxel correction for CSF contamination is essential for accurate interpretation of diffusion MRI findings in aging and disease.
- The Free Water Elimination (FWE) approach is a robust method for mitigating CSF partial volume effects.
- Findings have significant implications for understanding white matter changes in aging and neurological conditions.

