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UBC Theses and Dissertations

Mathematical modelling of the spatial dispersion of brain MRI lesions in multiple sclerosis Sheikhzadeh, Fahime


Many previous studies in multiple sclerosis (MS) have focused on the relationship between white matter lesion volume and clinical parameters, but few have investigated the independent contribution of the spatial dispersion of lesions to patient disability. In this thesis, we investigate whether a mathematical measure of the 3D spatial dispersion of lesions can reveal clinical significance that is independent of volume. Our hypothesis is that for any two given patients with similar lesion loads, the one with greater lesion dispersion would tend to have a greater disability. We investigate four different approaches for quantifying lesion dispersion and examine the ability of these lesion dispersion measures to act as potential surrogate markers of disability. We propose one connectedness-based measure (compactness), two region-based measures (ratio of minimum bounding spheres and ratio of lesion convex hull to the brain volume), two distance-based measures (Euclidean distance from a fixed point and pair-wise Euclidean distances) and one measure based on network theory (small-worldness). Our data include three sets of MRIs (n = 24, 174, 182) selected from two MS clinical trials. We segment all white matter lesions in each scan with a semi-automatic method to produce binary images of lesion voxels, quantify their spatial dispersion using the defined measures, then perform a statistical analysis to compare the dispersion values to total lesion volume and patient disability. We use linear and rank correlations to investigate the relationships between dispersion, disability, and total lesion volume, and regression analysis to investigate whether there is a potentially meaningful relationship between dispersion and disability, independent of volume. Our main finding is that one distance based measure, Euclidean distance from a fixed point, consistently correlates with disability score across all three datasets, and has predictive value that is at least partly independent of lesion volume. The results provide support for our hypothesis and suggest that a potentially meaningful relationship exists between patient disability and measurements of lesion dispersion. Finding such relationships can improve the understanding of MS and potentially lead to the discovery of novel surrogate biomarkers for clinical use in designing treatment trials and providing prognostic advice to individual patients.

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