Quantitative Perfusion Measurements in a Novel Large Animal Stroke Model

Stroke is a leading cause of death worldwide [1], and is the third leading cause of death and the leading cause of serious adult disability in New Zealand[2]. The aim of this project was to quantify perfusion changes in the brains of 20 sheep that underwent a novel surgical model of transient ischemic stroke. The sheep, with its large, gyrencephalic brain, presents a promising, potential animal model for stroke that could help to bridge the historical gap in translational research in stroke therapies [3]. However, we require that an animal model can replicate human patterns of disease in order for it to be a meaningful model for research into potential stroke therapies for humans. It was this replication of human patterns of disease, in terms of perfusion, thatwas under investigation in this project. Dynamic Contrast Enhanced (DCE) MRI images were obtained from each animal before stroke, and at 24 hours, 3 days, 6 days, and 28 days post-stroke. It was found that perfusion from the DCE-MRI series was quantifiable using the extended Tofts model in the form of the parameters Ktrans, ve and vp. The parameter values calculated from this project replicate known human patternsof disease in terms of global Ktrans changes in the affected hemisphere [4], which were found to increase by more than 60% in the stroke hemisphere,replicating the increased permeability following blood brain barrier breakdown.

In manually selected regions of cytotoxic and vasogenic edema, it was found that the estimated parameters in these regions replicated known perfusionchanges in these types of edema in humans [5]. Finally, the peak post-stroke permeability time point, as determined by Ktrans, was found to align exactlywith when we would expect vasogenic edema, a type of cerebral swelling that causes increased barrier permeability, to dominate in humans [5].

This thesis is the first time these DCE-MRI datasets have been analysed, and there remains a wealth of physiological and MRI data available forthis animal cohort. Avenues for future research include investigation into perfusion-diffusion mismatch in this animal model, further consideration ofindividual animal characteristics in analysis, and use of these results as a point of comparison for future research into pharmaceutical agents for treatment ofstroke, and in new non-contrast perfusion measurement techniques.