Microvascular brain pathology on high resolution MRI

Cerebral small vessel disease (SVD) is a common finding in the aging human brain and is associated with stroke, cognitive decline, and dementia. On autopsy, SVD encompasses pathological processes affecting small arteries and arterioles. Magnetic resonance imaging (MRI) detects the consequences of these pathological processes on the brain parenchyma, such as white matter hyperintensities, lacunar infarcts, and microbleeds. However, conventional MRI does not allow the detection of the whole spectrum of SVD, including the smaller parenchymal manifestations, such as cerebral microinfarcts (CMIs), and the vessel pathology itself. Moreover, parenchymal lesions on MRI considered to reflect SVD are not always the result of underlying changes to the small vessels. Ultra-high field strength (i.e. 7 tesla (T)) in vivo MRI and post-mortem MRI of brain tissue may overcome some of these issues and shed new light on cerebral SVD. The aim of the work described in this thesis was to zoom in on SVD and related brain changes, using both in vivo and post-mortem 7T MRI, and histopathology. A particular focus was to establish if CMIs could be detected in vivo and assess the clinical correlates of these microvascular lesions. In this thesis we showed that CMIs can indeed be detected in vivo. These findings were validated with post-mortem 7T MRI and histopathology. We proposed rating criteria for the identification of cortical CMIs on both 7T and 3T MRI, which allowed, for the first time, the study of CMIs in living patients and to track their impact on cognition and disease over time. The first results are promising and have already provided valuable clues on the role of cortical CMIs in cerebrovascular disease and dementia. Future studies should be directed towards understanding the longitudinal implications of CMIs in vivo, and to the pathophysiological mechanisms that drive CMI formation. Integrating insights from neuropathology and MRI will direct studies towards a better understanding of SVD and the development of new treatment options and prevention strategies of cognitive decline and dementia.