Magnetic resonance spectroscopy of the in vivo brain with semi-LASER

Changes in the metabolic state of the brain can occur, for example, as a result of neuronal activity or in pathologies such as cancer. In these cases, an altered energy demand can lead to changes in neurochemical concentrations detectable using proton magnetic resonance spectroscopy (1H-MRS). This thesis explores in vivo 1H-MRS methods for detection of such changes in the healthy and diseased brain. Specifically, this thesis aims to develop methods with semi-LASER localisation, thereby minimising the negative effects of chemical shift displacement and field inhomogeneity on spectral acquisition. Firstly, a Hadamard-encoded semi-LASER method for simultaneous measurement from two regions was developed at 7 T. Slice profiles, with low chemical shift displacement and small amounts of signal overlap, were revealed in phantom and in vivo. This was then implemented in a study of neurochemical change during positive and negative blood oxygen level-dependent (BOLD) responses. Negative BOLD responses are thought to reflect regions of neuronal suppression. A small decrease in ascorbate, as well as the T2*-induced linebroadening of several spectra, were observed in these regions. Furthermore, increases in glutamate and lactate were detected in positive BOLD regions. These findings suggested that negative BOLD may not be generated by an increase in local GABA concentration. Secondly, an optimised semi-LASER sequence (TE = 110 ms) at 3 T was shown to improve localisation of the oncometabolite 2-hydroxyglutarate (2-HG) â a product of IDH-mutation found in the majority of gliomas. This resulted in improved detection of 2-HG in patients compared to an existing technique. The method was also compared to 7 T, where benefits of an increased spectral resolution resulted in significantly better detection of 2-HG along with associated metabolites. This thesis highlights the importance of robust localisation for performing sensitive in vivo 1H-MRS neurochemical measurement in the human brain.