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The development of experimental models for NMR studies of neuropathology

West, Daniel Alexander; (2003) The development of experimental models for NMR studies of neuropathology. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Over the last decade, magnetic resonance imaging (MRI) and spectroscopy (MRS) have gained popularity as sensitive and safe investigations for use in the clinical and research environments. With the rapid growth in the availability of magnetic resonance hardware, there is great interest in applying it to the full spectrum of human disease processes, increasingly researchers are characterising the pathophysiology and natural history of disease in terms of MRI- and MRS-visible parameters. Such parameters may be structural, such as organ volume; biophysical such as diffusion, perfusion and temperature or biochemical such as metabolite concentrations and pH. The aim of the work presented in this thesis was to develop and characterise experimental models of focal cerebral ischaemia and Huntington's disease with respect to the NMR-visible changes in these conditions. A new model of focal cerebral ischaemia in the rat was developed specifically for NMR studies of stroke. It is shown that the model gives a reliable and reproducible lesion and enables the uninterrupted sampling of NMR data during the evolution of tissue damage. Multi-parametric MRI data were acquired which characterise the changes in water diffusion, tissue perfusion and proton NMR relaxation during and following cerebral ischaemia. Finally, the model was used to demonstrate regional activation of STAT-1 in the brain following ischaemia. STAT-1 has been shown to be important in regulating cell death in the heart and is a potential therapeutic target. In this study, MRI was used to define brain areas with different levels of haemodynamic disturbance which were analysed for STAT-1 activation following ischaemia or ischaemia-reperfusion injury. An existing transgenic mouse model of Huntington's disease, the R6/2 model, was characterised using quantitative in vivo magnetic resonance imaging and spectroscopy. Changes in proton spectroscopy and transverse relaxation were observed as a function of age and disease progression in affected mice. The potential use of magnetic resonance in the assessment of therapeutic strategies in the future is discussed.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: The development of experimental models for NMR studies of neuropathology
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Applied sciences; Health and environmental sciences; Magnetic resonance imaging; Spectroscopy
URI: https://discovery.ucl.ac.uk/id/eprint/10101881
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