CSF contamination contributes to apparent microstructural alterations in mild cognitive impairment

Diffusion MRI is used widely to probe microstructural alterations in neurological and psychiatric disease. However, ageing and neurodegeneration are also associated with atrophy, which leads to artefacts through partial volume effects due to cerebrospinal-fluid contamination (CSFC). The aim of this study was to explore the influence of CSFC on apparent microstructural changes in mild cognitive impairment (MCI) at several spatial levels: individually reconstructed tracts; at the level of a whole white matter skeleton (tract-based spatial statistics); and histograms derived from all white matter. 25 individuals with MCI and 20 matched controls underwent diffusion MRI. We corrected for CSFC using a post-acquisition voxel-by-voxel approach of free-water elimination. Tracts varied in their susceptibility to CSFC. The apparent pattern of tract involvement in disease shifted when correction was applied. Both spurious group differences, driven by CSFC, and masking of true differences were observed. Tract-based spatial statistics were found to be robust across much of the skeleton but with some localised CSFC effects. Diffusivity measures were affected disproportionately in MCI, and group differences in fornix microstructure were exaggerated. Group differences in white matter histogram measures were also partly driven by CSFC. For diffusivity measures, up to two thirds of observed group differences were due to CSFC. Our results demonstrate that CSFC has an impact on quantitative differences between MCI and controls. Furthermore, it affects the apparent spatial pattern of white matter involvement. Free-water elimination provides a step towards disentangling intrinsic and volumetric alterations in individuals prone to atrophy.