| White matter hyperintensities (WMH), detected by T2-weighted magnetic resonance imaging (MRI), are common in many neurological diseases as well as in healthy older individuals. Despite a common appearance on MRI, these hyperintensities represent distinct pathological processes, for example inflammatory demyelination in multiple sclerosis (MS) and ischemic or hypoxic changes in healthy aging. Greater WMH burdens have been found in cerebral amyloid angiopathy (CAA), Alzheimer's disease (AD), and cardiovascular disease (CVD) as compared to healthy elderly. It is unclear whether the increased volume of WMH in these disorders is related to a shared etiology of the primary disease, an incidental secondary pathogenic process leading independently to WMH, or several pathogenic processes leading to different types of WM damage that appear indistinguishable on MRI.; This thesis explores the spatial and contextual distribution of cerebral white matter damage in MS, CAA, AD, CVD, and healthy aging. Context-based morphometry (CBM) is a novel approach in which analysis is performed in a feature space defined by a particular anatomical or physiological characteristic. CBM was used to examine the relationship of WMH to the cerebrovascular architecture and normal cerebral perfusion pattern, in order to address the hypothesis that these factors influence the distribution of white matter damage in the brain by influencing pathogenesis or modulating the tissue repair capacity.; While many of these studies found similar spatial distributions of WMH, CBM yielded important insight into relationships between focal white matter damage and the pattern of normal cerebral perfusion. We present indirect evidence that normal perfusion pattern influences the persistence of white matter lesions in MS, such that lesions occurring in regions of lower relative perfusion appear to persist into the chronic phases of the disease. In all disease groups and healthy older individuals, WMH occurred most often in regions of lower perfusion. This work supports the overall hypothesis that sustained tissue damage and therefore disability result from lesion development in regions of lower relative perfusion in which the environment may be restrictive or prohibitive to normal reparative processes, such that it is within these regions that lesions will tend to persist rather than repair and resolve. |
