Tract based spatial statistics of the normal appearing white matter in the general elderly population
Year: 2008
Type: dissertation
Abstract: The role of cerebral white matter in intact brain functioning in older age is increasingly being recognized. Recent magnetic resonance (MR) imaging advances enable to non-invasively quantify structural integrity of normal appearing white matter. Studies into white matter integrity in the general elderly population, aim to gain insight into the pathophysiology of cognitive decline and neurodegenerative diseases such as dementia. Tract Based Spatial Statistics (TBSS), a novel analysis technique, allows the automated analysis of microstructural integrity in the tract centres of cerebral white matter. Fractional anisotropy images, derived from Diffusion Tensor MR data for every subject, are spatially normalized in a constrained manner. Subject specific measurements are then projected onto a skeleton of the common white matter structures to allow comparison of measurements between subjects. A feasibility study using TBSS was conducted in a small subject group. This study helped identify methodological components that needed adaptation or extension in order to analyse Tract Based Spatial Statistics of the normal appearing white matter in the general elderly population. In order to best drive the registration in the first stage of TBSS, a study specific template was established by crosswise registering all subjects' fractional anisotropy images. The time required for this operation was reduced by the adoption of a hierarchical registration scheme. To allow a specific focus on the normal appearing white matter, and thus to exclude visibly abnormal white matter, we used an existing white matter lesion segmentation. Once maps of white matter lesions were transformed into the subjects native space, we projected these maps onto the skeleton to earmark skeleton voxels originating in white matter lesions for subsequent exclusion in the statistical analysis. Furthermore, brain masking was improved, laterality is ascertained to be consistent between the different image processing pipelines and the followed TBSS pipeline was transformed to allow a large epidemiological cohort (N=832) to be processed. The latter modifications include adaptations to enable nonparametric permutation based multiple comparison correction in conjunction with a clustering approach. This thesis mainly addresses the methodological extensions and adaptations implemented to allow the proposed analysis. A manuscript "White matter atrophy and lesion formation explain the loss of structural integrity of white matter in aging" is included in Appendix 2. This manuscript, accepted for publication in NeuroImage, introduces the adaptations and extensions, but most importantly describes the application of the developed methodology and the conclusions that can be derived from the obtained results. The successful application of the adapted methodology offers numerous opportunities for future research. The aggregation of tract-specific measures derived from diffusion tensor MR images into imaging based biomarkers for early diagnosis of neurodegenerative diseases can be investigated. A first start will be made in studying the cingulate bundle. Another future direction is to define local measures to describe lesion load or white matter atrophy. This would yield insight into the link between macrostructural white matter changes, lesion formation and atrophy, and microstructural properties derived with diffusion tensor MR.
Author: Marius de Groot
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W33395299