This thesis describes the development of magnetic resonance imaging (MRI) techniques to visualise neurofibrillary tau pathology in transgenic mice. Neurofibrillary pathology is a prominent pathological feature of Alzheimer's disease (AD) and is closely correlated to cognitive impairment and dementia. 19F and 1H MRI methods were developed with a 4.7 T preclinical system. To facilitate these experiments, RF saddle coils were designed and constructed that show good agreement with theoretical SNR calculations and produce uniform B1 fields. A copper wire surface coil, incorporating active decoupling electronics, was built to increase the sensitivity of 19F and 1H mouse brain experiments. A stripline transmission line resonator (TLR) was also developed as a surface coil receiver and because it does not need tuning and matching adjustments, it reduces experimental set up times significantly. An ultra-short echo time (UTE) pulse sequence was developed for imaging 19F compounds, designed to attach to sites of tau pathology in the brain and which were known to exhibit very short T2 relaxation times. Ex vivo, 19F MRI experiments using these compounds indicated low penetration of the blood brain barrier and a tendency for precipitation. An RF spoiled, short TE 3D gradient echo pulse sequence was optimised to produce artefact-free T1-weighted images of the mouse brain. Measurements from a preliminary study using high resolution, T1-weighted MRI showed that the ventricular areas of a control mouse were not appreciably different from those of a transgenic mouse. Software was developed to generate automated T2 brain maps from spin echo MRI data sets and was used to compare T2 relaxation times between a control and a transgenic mouse. This experiment showed that the T2 relaxation times of the tau transgenic mouse brain were prolonged when compared to those of a control mouse.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:600047 |
| Date | January 2010 |
| Creators | Lavdas, Ioannis |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=203818 |
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