The overall goal of my group is to develop advanced magnetic resonance spectroscopy and imaging techniques and to apply them and related methods to studying brain metabolism and neurotransmission in both human subjects and in animal models. Magnetic resonance spectroscopy, in principle, allows measurement of neurotransmitter GABA, which plays an important role in many psychiatric diseases including depression and schizophrenia, and its metabolism. In reality, such measurement is fraught with technical difficulties. During 2002-2003, significant progress was made in the development of new spectroscopic techniques for single-voxel GABA measurement and for spectroscopic imaging of GABA, resulting in improved reliability and sensitivity. First we demonstrated that universal spin rotation can be achieved by creating a temporally symmetric gradient-RF pulse based on the sinc pulses. This allowed us to design a novel spatial localization scheme for double quantum filtering by converting the double quantum preparation pulse into a spatially selective one. By incorporating this new localization technique into our previous doubly selective multiple quantum filter we were able to achieve three-dimensional spatial localization and doubly selective double quantum filtering in a single shot, eliminating the necessity for using subtraction-based ISIS for localization. In addition to the benefit of suppressing overlapping creatine, glutathione and macromolecules by the use of doubly selective multiple quantum filtering, our single-shot scheme greatly reduces errors due to patient movement during the scanning. The elimination of ISIS also allowed us to further develop a two-echo method for simultaneous detection of double quantum filtered GABA and single quantum creatine in one scan and to successfully convert this GABA method into a spectroscopic imaging method for the measurement of GABA distribution across the brain as well as between gray and white matters. A manuscript describing the single-voxel two-echo method will soon be submitted for publication. Currently, we have extended this method for spectroscopic imaging of GABA. Efforts are being made to use T1-based image segmentation and SLIM methods to quantify GABA concentration in gray and white matters in the human brain in vivo. Significant progress has also been made in optimization of high-field spectroscopy and imaging at 11.7 Tesla for studying brain metabolism and neurotransmission in rodent models. A new phase mapping method was devised to measure and correct static magnetic field inhomogeneity up to the 4th order. This new method uses six linear columns to sample field distortion within the selected brain slice and unequivocally determines the in-slice field inhomogeneity to the 4th order. As a result, high quality in vivo proton spectroscopic data and echo-planar imaging data have been obtained from the rat somatosensory cortex. Work is currently on-going to apply proton spectroscopy to studying neurotransmitter metabolism in rodents.