Absolute quantification of oxygen metabolism in the human brain using FMRI
To produce energy and maintain healthy function the brain requires a steady supply of oxygen which if interrupted results in impaired function and tissue damage. Oxygen metabolism is therefore presented as a desirable physiological function to measure as it is closely linked with brain tissue function and health. Recently an MRI method was introduced capable of measuring absolute oxygen metabolism in the brain. The technique is based on using both hypercapnic and hyperoxic respiratory challenges to calibrate the blood oxygen level dependent (BOLD) functional MRI (FMRI) signal. The aim of this thesis is to further develop this promising technique, referred to here as dual calibrated FMRI (dcFMRI), proving its suitability for application in further studies of oxygen metabolism in the brain.\ud Initially, in this thesis, the role of oxygen metabolism in energy production, brain function and disease is discussed. To motivate the development of dcFMRI a review of current measurement techniques is presented followed by an introduction to the basic MRI concepts underpinning the dcFMRI approach. The dcFMRI technique is then described in detail.\ud The optimal ASL acquisition available in our centre for application in the dcFMRI measurement was experimentally investigated, allowing a dcFMRI protocol to be implemented. A comparison of dcFMRI respiratory designs, for detecting regional changes in oxygen metabolism, was made and the within and between session repeatability of these measurements were assessed. In order to make the technique more clinically feasible, reductions in acquisition time were assessed using a retrospective analytical approach. The ability of dcFMRI to detect global flow related changes in oxygen metabolism was demonstrated and a novel dcFMRI approach was implemented. This availed of an R2' based measure to replace the hypercapnic respiratory challenge in the dcFMRI protocol. Potential areas for future work and further application of the dcFMRI technique are then considered.