Magnetic resonance imaging of cerebral oxygen consumption and perfusion

This dissertation describes both methodological developments in quantitative functional magnetic resonance imaging (fMRI) of cerebral oxygen consumption, and the results of experiments using these techniques to elucidate the mechanisms linking focal changes in blood flow and oxygen metabolism. Technical contributions presented include a novel MRI pulse sequence for simultaneously monitoring cerebral blood flow and tissue oxygenation with high signal-to-noise ratio, as well as an experiment automation system permitting complex multiparametric studies to be carried out efficiently in large numbers of subjects. These tools enabled us to make a number of significant neurophysiological discoveries with important implications for the design and interpretation of fMRI experiments. In particular, relative changes in cerebral perfusion and oxygen consumption were found to be coupled in a consistent linear ratio of approximately 2:1, respectively, in human visual cortex. A quantitative model predicting that oxygenation-sensitive MRI signals must be extremely sensitive to departures from this coupling ratio was also introduced, revealing that combined perfusion/oxygenation measurement during graded activation is a powerful tool for studying regulatory relationships between these parameters. Predictions based on this model were in excellent agreement with experimental results, supporting model-derived estimates of oxygen consumption and suggesting that the ∼2:1 coupling discovered in visual cortex is likely to apply in most cortical systems. Finally, important non-linear characteristics of fMRI signal dynamics in human visual cortex were revealed, challenging current models of fMRI transient response