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CSF contamination contributes to apparent microstructural alterations in mild cognitive impairment
Rok Berlot1, Claudia Metzler-Baddeley2, Derek K Jones2
1Department of Clinical Neuroscience, Institute of Psychiatry, King's College London, 16 De Crespigny Park, London SE5 8AF, UK; Department of Neurology, University Medical Centre Ljubljana, Zaloska 2, 1000 Ljubljana, Slovenia.
Abstract:
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.
Insights
Cerebrospinal fluid contamination (CSFC) significantly impacts diffusion MRI findings in mild cognitive impairment (MCI). Correcting for CSFC using free-water elimination reveals true microstructural changes and alters the apparent pattern of white matter involvement in disease.
Area of Science:
- Neuroimaging
- Neurology
- Biomedical Engineering
Background:
- Diffusion MRI is crucial for detecting microstructural changes in neurological diseases.
- Ageing and neurodegeneration cause atrophy, leading to cerebrospinal fluid contamination (CSFC) artifacts in diffusion MRI.
- Understanding CSFC's influence is vital for accurate disease assessment.
Purpose of the Study:
- To investigate the impact of CSFC on apparent microstructural changes in mild cognitive impairment (MCI).
- To analyze CSFC effects at multiple spatial scales: individual tracts, white matter skeleton, and histograms.
- To evaluate the efficacy of free-water elimination for correcting CSFC-induced artifacts.
Main Methods:
- Diffusion MRI scans were acquired from 25 individuals with MCI and 20 healthy controls.
- A voxel-by-voxel free-water elimination method was employed for post-acquisition CSFC correction.
- Analysis included tract-level, tract-based spatial statistics (TBSS), and white matter histogram approaches.
Main Results:
- CSFC significantly influenced apparent microstructural differences between MCI patients and controls, affecting up to two-thirds of diffusivity measure differences.
- The apparent spatial pattern of white matter involvement in MCI shifted after CSFC correction.
- TBSS showed robustness across most of the white matter skeleton, with localized CSFC effects; fornix microstructure differences were exaggerated by CSFC.
Conclusions:
- CSFC introduces significant quantitative and spatial artifacts in diffusion MRI studies of MCI.
- Free-water elimination is a valuable method for distinguishing true microstructural alterations from volumetric changes caused by atrophy.
- Accurate interpretation of diffusion MRI in atrophic conditions like MCI requires robust CSFC correction.
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