Lythgoe, Mark F; (1999) Studies of experimental cerebral ischaemia using magnetic resonance imaging and autoradiography. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Following a stroke, the ability to discriminate between areas of non-recoverable tissue and potentially salvageable tissue remains a goal of diagnostic imaging. There have been a number of recent developments both in nuclear medicine and in magnetic resonance imaging (MRI) techniques, which may have potential to achieve this goal. This thesis describes the use of these techniques for the evaluation of focal pathophysiology in a rat model of model cerebral artery occlusion (MCAO). Methods were described to use autoradiographic markers to study cerebral blood flow (99mTc-hexamethylpropylene amine oxime) and cerebral hypoxia (125I-iodoazomycin arabinoside) simultaneously following MCAO in the rat. The uptake of these tracers was compared to MRI measurements of the apparent diffusion coefficient of water (ADC) and to histology. It was shown that the combined use of 125I-IAZA or ADC imaging with perfusion imaging may allow differentiation between areas of oligaemic misery perfusion, ischaemic misery perfusion and ischaemic lesion core. MRI was used to examine the effects of cerebral tissue anisotropy on calculation of the spatial distribution of ischaemia in the rat using ADC measurements. Demonstration of grey matter anisotropy led to the use of rotationally invariant ADC measurements which were shown to improve stroke lesion delineation. To investigate the acute changes in NMR parameters of diffusion, perfusion, T1 and T2 a remote controlled MCAO model in the rat was refined for a vertical 8.5T high field magnet. Combined perfusion and diffusion data distinguish between a "moderately affected area", with reduced perfusion but normal diffusion; and a "severely affected area", in which both perfusion and diffusion were significantly reduced. Two novel MRI observations were reported, namely a decrease in T2 and an increase in T1, both within the first few minutes of ischaemia. A rat model of oligaemic misery perfusion was developed in which a large region of homogeneously reduced blood flow was produced without cytotoxic oedema forming. Early NMR changes in CBF, T1 and T2 were noted without reduction in the ADC value. This approach may provide a model of penumbral flow, which may be of value in studying and evaluating neuroprotection.

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