Measuring Neurotransmitter Cycling

Understanding neuronal metabolism is critical for studies of brain function, and magnetic resonance spectroscopy (MRS) of infused 13C-labeled substrates is well established as the only noninvasive in-vivo technique capable of measuring glutamate neurotransmitter cycling and cell-specific neuroenergetics in both normal and diseased states. Using metabolic modeling, in vivo 13C MRS studies have successfully compared neuronal and glial energy metabolism, elucidated the linkage between neuroenergetics and neurotransmitter cycling, and identified altered brain metabolism in multiple neurological and psychiatric diseases. 

Human studies, however, are technically challenging due to low sensitivity, complex overlapping spectra, and the need for high-power decoupling.  In this project, we are developing a novel family of 1H-13C MRS MRS pulse sequences to address current limitations and improve measurements of neuronal and glial TCA fluxes and glutamate/glutamine cycling rates.  The focus is on ultra-high field (≥7 T) indirect detection methods that maximize sensitivity in order to interrogate small tissue regions (~1 cc) throughout the human brain within acceptable scan times.