Hyperpolarized 129Xe as an NMR probe for functional studies

The nuclear spin polarization of "1"2"9Xe can be enhanced by several orders of magnitude using optical pumping techniques, resulting in a dramatic enhancement of the "1"2"9Xe Nuclear Magnetic Resonance (NMR) signal. The 'hyperpolarized' gas can be used for Magnetic Resonance Imaging (MRI) of the void spaces of the lungs after introduction of the gas into the respiratory system. Furthermore, the high solubility of xenon in blood and lipids suggests the use of "1"2"9Xe NMR for studying blood flow, permeability, perfusion and blood volume. Hyperpolarized "1"2"9Xe MRI has the potential of combining the high sensitivity and functional information of radioactive tracer studies with the high spatial and temporal resolution of MRI. The spin-lattice relaxation time T_1 of "1"2"9Xe in blood determines the loss of polarization during transit from the lungs to the tissue of interest. A difference in the relaxation times of xenon in oxygenated and deoxygenated blood could be used as a contrast mechanism in functional Magnetic Resonance Imaging (fMRI). In this thesis, the hyperpolarized "1"2"9Xe T_1 in human blood is measured in vitro as a function of blood oxygenation, and the relevant relaxation mechanisms are discussed. A new and unexpected finding is that the hyperpolarized "1"2"9Xe NMR spectrum in blood is highly sensitive to blood oxygenation. Therefore, hyperpolarized "1"2"9Xe NMR provides a powerful means of measuring blood oxygenation quantitatively and non-invasively. The interaction of xenon with hemoglobin is responsible for an oxygen-dependent shift of the "1"2"9Xe NMR resonance of xenon in red blood cells. Injection delivery of hyperpolarized "1"2"9Xe in solution could be a more efficient method of administrating the gas for functional NMR studies. For this purpose, suitable biocompatible carrier media have been studied. In particular, the use of perfluorocarbon emulsions, which are already in use as blood substitutes, as delivery media for hyperpolarized "1"2"9Xe has been investigates. Preliminary in vivo results are presented, together with the first hyperpolarized "1"2"9Xe NMR measurements in tumour models. (author)Available from British Library Document Supply Centre-DSC:DXN042009 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo