Iron is the most abundant trace metal in the brain and is essential for many biological processes, such as neurotransmitter synthesis and myelin formation. This thesis investigates small, multifocal hypointensities that are apparent on T2*- weighted (T2*w) MRI in the basal ganglia, where presumably most iron enters the brain via the blood-brain-barrier along the penetrating arteries. These basal ganglia T2*w hypointensities are believed to arise from iron-rich microvascular mineral deposits, which are frequently found in community-dwelling elderly subjects and are associated with age-related cognitive decline. This thesis documents the characteristic spatial distribution and morphology of basal ganglia T2*w hypointensities of 98 community-dwelling, elderly subjects in their seventies, as well as their imaging signatures on T1-weighted (T1w) and T2- weighted (T2w) MRI. A fully automated, novel method is introduced for the segmentation of basal ganglia T2*w hypointensities, which was developed to reduce the high intra- and inter-rater variability associated with current semi-automated segmentation methods and to facilitate the segmentation of these features in other single- and multi-centre studies. This thesis also presents a multi parametric quantitative MRI relaxometry methodology for conventional clinical MRI scanners that was developed and validated to improve the characterisation of brain iron. Lastly, this thesis describes the application of the developed methods in the segmentation of basal ganglia T2*w hypointensities of 243 community-dwelling participants of the Austrian Stroke Prevention Study Family (ASPS-Fam) and their analysis on R2* (=1/T2*) relaxation rate and Larmor frequency shift maps. This work confirms that basal ganglia T2*w hypointensities, especially in the globus pallidus, are potentially MRI markers of microvascular mineralization. Furthermore, the ASPS-Fam results show that basal ganglia mineral deposits mainly consist of paramagnetic particles, which presumably arise from an imbalance in the brain iron homeostasis. Hence, basal ganglia T2*w hypointensities are possibly an indicator of age-related microvascular dysfunction with iron accumulation, which might help to explain the variability of cognitive decline in normal ageing.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:721183 |
| Date | January 2016 |
| Creators | Glatz, Andreas |
| Contributors | Bastin, Mark ; Wardlaw, Joanna ; Valdes Hernandez, Maria |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/22905 |
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