The treatment of hyperacute ischaemic stroke has been revolutionised by the concept of potentially salvageable tissue – the ‘ischaemic penumbra’. However, current therapeutic practice is to administer thrombolytic therapy with recombinant tissue plasminogen activator after exclusion of intra-cerebral haemorrhage, with ‘time since onset’ used as a surrogate marker for the presence or absence of the ischaemic penumbra. The ability to identify the penumbra on an individual basis would enable bespoke treatment plans on the basis of underlying pathophysiology. The most commonly employed penumbral image technique is multi-modal magnetic resonance imaging (MRI) to identify a region of perfusion-diffusion mismatch. However, this approach remains to be validated. Moreover, a systematic review presented as an appendix to this thesis highlights the marked heterogeneity for its application.
This thesis focusses on the development of a novel MRI technique (Oxygen Challenge) and is the first to report findings from human acute ischaemic stroke. The rationale for this technique is that it is sensitive to deoxyhaemoglobin, which is produced as a consequence of oxidative metabolism. It therefore has the potential to discriminate tissue compartments based on metabolic activity. For this study, 35 subjects with acute ischaemic stroke were imaged with transient hyperoxia (Oxygen Challenge) applied during continuous T2*-weighted MRI. Exploratory analyses suggested the following;
•Oxygen Challenge precipitates a T2*-weighted signal increase in healthy tissue
•This signal increase is partly dependent on the underlying cerebral blood volume, as suggested by univariate and multivariate analyses
•In general, higher concentrations of oxygen precipitate greater T2*-weighted signal increases, but oxygen may influence T2*-weighted signal intensity in a bi-modal manner
•The signal changes in operationally defined infarct core are attenuated, suggesting a metabolic influence on Oxygen Challenge results
•Signal increases in the hyperacute perfusion-diffusion mismatch region were sometimes exaggerated, consistent with increased oxygen extraction fraction. However, small volumes of tissue acquired from only a few subjects limited definitive conclusions in this study
•Oxygen Challenge may detect regions of crossed cerebellar diaschsis, although further confirmation is required
•Maps of ‘percentage signal change’ allowed rapid evaluation of whole brain Oxygen Challenge data
•Improvements in signal-to-noise ratio are required before this technique can be applied in clinical practice.
On the basis of these data it is concluded that the technique is encouraging and further validation is warranted
