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DTI measures in crossing-fibre areas: increased diffusion anisotropy reveals early white matter alteration in MCI and mild Alzheimer's disease.

ABSTRACT: Though mild cognitive impairment is an intermediate clinical state between healthy aging and Alzheimer's disease (AD), there are very few whole-brain voxel-wise diffusion MRI studies directly comparing changes in healthy control, mild cognitive impairment (MCI) and AD subjects. Here we report whole-brain findings from a comprehensive study of diffusion tensor indices and probabilistic tractography obtained in a very large population of healthy controls, MCI and probable AD subjects. As expected from the literature, all diffusion indices converged to show that the cingulum bundle, the uncinate fasciculus, the entire corpus callosum and the superior longitudinal fasciculus are the most affected white matter tracts in AD. Significant differences between MCI and AD were essentially confined to the corpus callosum. More importantly, we introduce for the first time in a degenerative disorder an application of a recently developed tensor index, the "mode" of anisotropy, as well as probabilistic crossing-fibre tractography. The mode of anisotropy specifies the type of anisotropy as a continuous measure reflecting differences in shape of the diffusion tensor ranging from planar (e.g., in regions of crossing fibres from two fibre populations of similar density or regions of "kissing" fibres) to linear (e.g., in regions where one fibre population orientation predominates), while probabilistic crossing-fibre tractography allows to accurately trace pathways from a crossing-fibre region. Remarkably, when looking for whole-brain diffusion differences between MCI patients and healthy subjects, the only region with significant abnormalities was a region of crossing fibres in the centrum semiovale, showing an increased mode of anisotropy. The only white matter region demonstrating a significant difference in correlations between neuropsychological scores and a diffusion measure (mode of anisotropy) across the three groups was the same region of crossing fibres. Further examination using probabilistic tractography established explicitly and quantitatively that this previously unreported increase of mode and co-localised increase of fractional anisotropy was explained by a relative preservation of motor-related projection fibres (at this early stage of the disease) crossing the association fibres of the superior longitudinal fasciculus. These findings emphasise the benefit of looking at the more complex regions in which spared and affected pathways are crossing to detect very early alterations of the white matter that could not be detected in regions consisting of one fibre population only. Finally, the methods used in this study may have general applicability for other degenerative disorders and, beyond the clinical sphere, they could contribute to a better quantification and understanding of subtle effects generated by normal processes such as visuospatial attention or motor learning.

SUBMITTER: Douaud G

PROVIDER: S-EPMC7116583 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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DTI measures in crossing-fibre areas: increased diffusion anisotropy reveals early white matter alteration in MCI and mild Alzheimer's disease.

Douaud Gwenaëlle G Jbabdi Saâd S Behrens Timothy E J TE Menke Ricarda A RA Gass Achim A Monsch Andreas U AU Rao Anil A Whitcher Brandon B Kindlmann Gordon G Matthews Paul M PM Smith Stephen S

NeuroImage 20101221 3

Though mild cognitive impairment is an intermediate clinical state between healthy aging and Alzheimer's disease (AD), there are very few whole-brain voxel-wise diffusion MRI studies directly comparing changes in healthy control, mild cognitive impairment (MCI) and AD subjects. Here we report whole-brain findings from a comprehensive study of diffusion tensor indices and probabilistic tractography obtained in a very large population of healthy controls, MCI and probable AD subjects. As expected ...[more]

PMID: 21182970

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Project description:Background: Mild traumatic brain injuries (mTBIs) are a significant social, sport, and military health issue. In spite of advances in the clinical management of these injuries, the underlying pathophysiology is not well-understood. There is a critical need to advance objective biomarkers, allowing the identification and tracking of the long-term evolution of changes resulting from mTBI. Diffusion-weighted imaging (DWI) allows for the assessment of white-matter properties in the brain and shows promise as a suitable biomarker of mTBI pathophysiology. Methods: 34 individuals within a year of an mTBI (age: 24.4 ± 7.4) and 18 individuals with no history of mTBI (age: 23.2 ± 3.4) participated in this study. Participants completed self-report measures related to functional outcomes, psychological health, post-injury symptoms, and sleep, and underwent a neuroimaging session that included DWI. Whole-brain white matter was skeletonized using tract-based spatial statistics (TBSS) and compared between groups as well as correlated within-group with the self-report measures. Results: There were no statistically significant anatomical differences between the two groups. After controlling for time since injury, fractional anisotropy (FA) demonstrated a negative correlation with sleep quality scores (higher FA was associated with better sleep quality) and increasing depressive symptoms in the mTBI participants. Conversely, mean (MD) and radial diffusivity (RD) demonstrated positive correlations with sleep quality scores (higher RD was associated with worse sleep quality) and increasing depressive symptoms. These correlations were observed bilaterally in the internal capsule (anterior and posterior limbs), corona radiata (anterior and superior), fornix, and superior fronto-occipital fasciculi. Conclusion: The results of this study indicate that the clinical presentation of mTBI, particularly with respect to depression and sleep, is associated with reduced white-matter integrity in multiple areas of the brain, even after controlling for time since injury. These areas are generally associated not only with sleep and emotion regulation but also cognition. Consequently, the onset of depression and sleep dysfunction as well as cognitive impairments following mTBI may be closely related to each other and to white-matter integrity throughout the brain.

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Dataset Information

DTI measures in crossing-fibre areas: increased diffusion anisotropy reveals early white matter alteration in MCI and mild Alzheimer's disease.

Publications

DTI measures in crossing-fibre areas: increased diffusion anisotropy reveals early white matter alteration in MCI and mild Alzheimer's disease.

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