This study presents the detection of [2-13 C]glucose metabolism in the carboxylic/amide region in the human brain, and demonstrates that the cerebral metabolism of [2-13 C]glucose can be studied in human subjects in the presence of severe hardware constraints of widely available 3 T clinical scanners and with low-power stochastic decoupling. In the carboxylic/amide region of human brain, the primary products of 13 C label incorporation from [2-13 C]glucose into glutamate, glutamine, aspartate, ␥-aminobutyric acid, and N-acetylaspartate were detected. Unlike the commonly used alkanyl region where lipid signals spread over a broad frequency range, the carboxylic carbon signal of lipids was found to be confined to a narrow range centered at 172.5 ppm and present no spectral interference in the absence of lipid suppression. Comparison using phantoms shows that stochastic decoupling is far superior to the commonly used WALTZ sequence at very low decoupling power at 3 T. It was found that glutamine C1 and C5 can be decoupled using stochastic decoupling at 2.2 W, although glutamine protons span a frequency range of Ϸ700 Hz. Detailed specific absorption rate analysis was also performed using finite differ- Proton decoupled 13 C magnetic resonance spectroscopy (MRS) is a useful noninvasive method to study animal and human brain in vivo. With the enhanced 13 C signal due to exogenous [1-13 C]glucose infusion, the turnover of important metabolites in human brain can be quantitatively measured (1-14). Using 13 C MRS as an investigative tool for human diseases has also been successful (15-17). However, in vivo 13 C MRS in human brain has encountered more technical challenges than animal studies. One of the major difficulties has been associated with the need to decouple large 1 H-13 C scalar couplings ( 1 J CH ϭ 125-145 Hz) for alkanyl carbons of major brain metabolites. In order to achieve effective decoupling, the RF field strength of decoupling pulses (␥B 2 ) has to be much greater than 1 J CH . Because chemical shift dispersion is proportional to static magnetic field strength, the proton decoupling bandwidth and, therefore, the ␥B 2 required for broadband decoupling, increase linearly with ␥B 0 . As a result, the RF power required for broadband proton decoupling increases as a function of (␥B 0 ) 2 and has to be carefully controlled in order to keep the specific absorption rate (SAR) under the safety guidelines established by the US Food and Drug Administration (FDA) (18) and the International Electrotechnical Commission (IEC) (19). To obtain necessary RF efficiency with acceptable RF power deposition, most human studies have used surface or half-volume transceiver coils for proton decoupling (20). As a result, nearly all of the human 13 C studies have been performed in the occipital lobe of human brain, partially in order to avoid potential damage to the human eye as a result of poor perfusion due to RF heating from proton decoupling pulses (21-23).Even at magnetic field strengths currently accessible to most clinical ...
Vigabatrin and gabaculine, both highly specific inhibitors of GABA (gamma-aminobutyric acid) transaminase, cause significant elevation of endogenous GABA levels in brain. The time course of GABA concentration after acute GABA transaminase inhibition was measured quantitatively in the alpha-chloralose-anesthetized rat brain using in vivo selective homonuclear polarization transfer spectroscopy. The blood oxygenation level-dependent (BOLD) effect in functional magnetic resonance imaging (fMRI) has been considered to be coupled tightly to neuronal activation via the metabolic demand of associated glutamate transport. Correlated with the rise in endogenous GABA level after vigabatrin or gabaculine treatment, the intensity of BOLD-weighted fMRI signals in rat somatosensory cortex during forepaw stimulation was found to be reduced significantly. These results are consistent with previous findings that inhibition of GABA transaminase leads to augmented GABA release and potentiation of GABAergic inhibition.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.