In Vivo Magnetic Resonance Spectroscopy (MRS) of the Activated Human Brain at 7T

The principal aim of this thesis was to investigate human brain energy metabolism during physiological activation using proton (1H) magnetic resonance spectroscopy (MRS) at 7 Tesla (T). High magnetic fields (≥ 7 T) provide several advantages in human brain imaging and spectroscopy. In particular, signal-to-noise ratio (SNR) and chemical shift dispersion increase at higher magnetic fields, allowing for improved accuracy and precision of metabolite quantification. To take profit of the benefits of MRS at high field, one needs to provide an advanced methodology including hardware, pulse sequences experimental setup and data analysis. Each of these aspects was thoroughly explored in this thesis. In the field of functional studies, functional MRS (fMRS) has recently been used as a research tool to investigate the neuroenergetic and metabolic basis of physiologic brain activation. It provides direct insight into brain metabolism by non-invasively determining concentrations of metabolites. This is critical for the basic understanding of overall brain function, and potentially of the pathogenesis of many neurodegenerative diseases. In general, an optimized MR system and accurate acquisition methodology are required for high sensitivity and reliable metabolite quantification. The metabolites of interest for fMRS studies (e.g. lactate, glucose) are present in low concentration and metabolite changes are small under activation. Hence, studies of metabolite changes, in particular lactate, have led to inconsistent reports in the literature over the last decades. To address these challenges, it was essential to develop a robust MR protocol for the quantitative measurement of metabolite changes. A fMRS study was performed to investigate metabolite changes during visual stimulation using the enhanced sensitivity of the SPin ECho full Intensity Acquired Localized (SPECIAL) sequence. Small but significant increases of lactate (19 ± 4 %, P < 0.05) and glutamate (4 ± 1 %, P < 0.001) were observed using a small number of subjects (n = 6). With the exception of glucose (12 ± 5 %, P < 0.001), no other significant metabolite concentration changes beyond experimental error were observed. Based on this successful fMRS study, we further investigated brain energy metabolism. A subsequent fMRS study was performed to determine metabolite changes occurring during motor activation in the human brain. This second study demonstrated that increases in lactate (17 ± 5 %, P < 0.001) and glutamate (2 ± 1 %, P < 0.005) during motor stimulation were small, but similar to those observed during visual stimulation. These metabolite changes were further analyzed, and they supported the hypothesis of an increase in the change of cerebral metabolic rate of oxygen, ∆CMRO2, that is transiently lower than that of glucose, ∆CMRGlc, during the first one to two minutes of stimulation. Finally, we hypothesized that the observed glutamate and lactate increases were a general manifestation of the blo