13C MRS studies of neuroenergetics and neurotransmitter cycling in humans

Abstract

In the last 25years, 13C MRS has been established as the only noninvasive method for the measurement of glutamate neurotransmission and cell-specific neuroenergetics. Although technically and experimentally challenging, 13C MRS has already provided important new information on the relationship between neuroenergetics and neuronal function, the energy cost of brain function, the high neuronal activity in the resting brain state and how neuroenergetics and neurotransmitter cycling are altered in neurological and psychiatric disease. In this article, the current state of 13C MRS as it is applied to the study of neuroenergetics and neurotransmitter cycling in humans is reviewed. The focus is predominantly on recent findings in humans regarding metabolic pathways, applications to clinical research and the technical status of the method. Results from invivo 13C MRS studies in animals are discussed from the standpoint of the validation of MRS measurements of neuroenergetics and neurotransmitter cycling, and where they have helped to identify key questions to address in human research. Controversies concerning the relationship between neuroenergetics and neurotransmitter cycling and factors having an impact on the accurate determination of fluxes through mathematical modeling are addressed. We further touch upon different 13C-labeled substrates used to study brain metabolism, before reviewing a number of human brain diseases investigated using 13C MRS. Future technological developments are discussed that will help to overcome the limitations of 13C MRS, with special attention given to recent developments in hyperpolarized 13C MRS. © 2011 John Wiley & Sons, Ltd.