Magnetic Resonance Spectroscopy and Imaging Studies of Brain Functions

National Institute Of Mental Health

Investigators

Linked publications, trials & patents

Abstract

The goal of this research is to develop advanced magnetic resonance spectroscopy (MRS) and imaging (MRSI) techniques and to apply them and other complementary methods to study brain metabolism, neurotransmission, and enzyme activity. MRS allows in vivo measurement of the neurotransmission of glutamate and GABA, which play important roles in many major psychiatric diseases, including depression and schizophrenia. We strive to push technological boundaries to access previously unreachable chemical information about the brain and to eliminate technical barriers to the clinical application of carbon-13 MRS techniques. Conventional carbon-13 MRS approaches require scanners with a broadband channel and specialized or custom-made hardware. Furthermore, the high radiofrequency power required for broadband heteronuclear decoupling makes it impossible to use conventional carbon-13 MRS to study the frontal cortex. This region is crucial for higher cognitive functions such as regulating emotions, social interactions, and personality, and abnormalities in it are linked to many mental disorders. In FY2025, we developed a novel spectral editing technique for isolating glutamate, glutamine, and glutathione at 3 Tesla—the prevailing magnetic field strength for clinical studies. By spectrally editing the aspartyl moiety of N-acetylaspartate and optimizing the echo time, we successfully “cleaned up” the crowded proton spectra and achieved clear visual separation of these three important spectroscopic biomarkers of various brain disorders. More importantly, with the administration of carbon-13 labeled glucose, we demonstrated that our method enables monitoring of glutamate turnover using the high sensitivity and spatial resolution of proton MRS, with spectrally resolved glutamate at 3 Tesla. Since only standard, commercially available hardware was used, our technique can be easily implemented on other 3 Tesla scanners, enabling dynamic glutamate turnover studies at virtually all sites equipped with such systems. This work has been submitted for publication in Magnetic Resonance in Medicine. At 7 Tesla, we demonstrated that our technique for encoding molecular transverse relaxation can be enhanced to measuring the concentration and T2 of lactate, the primary marker of glycolysis. With this enhancement we also increased the glutamate signal amplitude by 47%. Together, our T2 technique significantly enhanced the detection of Glu and enabled the detection of Lac for measuring both the concentration and T2 of the markers of oxidative metabolism and glycolysis. This work has been published (L. An, S. Hong, T. Turon, A. Pavletic, C.S. Johnson, J.A. Derbyshire, and J. Shen, Enhanced detection of glutamate via transverse relaxation encoding with narrowband decoupling in the human brain, Magn. Reson. Med., 93:2278-2286 (2025)). In FY2025, we also completed the development of a 7 Tesla proton MRS technique for reliably detecting the GABA H2 signal—a highly sensitive marker for GABA metabolism. Most importantly, we demonstrated the capability of our method for real-time monitoring of GABA metabolism. We successfully collected time-course data on dynamic GABA turnover in the human brain—the first study of its kind. Because our method is proton-only and uses standard, commercially available hardware, it can be implemented at all 7 Tesla sites, making studies of GABA metabolism broadly accessible. This work has been published (L. An, S. Hong, T. Turon, A. Pavletic, C.S. Johnson, J.A. Derbyshire, and J. Shen, In vivo GABA detection by single-pulse editing with one shot. Magn. Reson. Med., 94:4-14 (2025)).