In addition to provide technical support on developed MRS protocols, significant progress have been made in developing new spectroscopy protocols for studying patients. ? ? By measuring the turnover of glutamate, glutamine and GABA from carbon-13-labeled glucose, carbon-13 MRS provides information on brain energetics, glutamate-glutamine cycling, and GABA synthesis. We have first developed and tested two carbon-13 MRS methods using monkeys: a single-shot INEPT-based polarization transfer methods for detecting the methylene and alpha-carbons using 1-13Cglucose; a method for detecting the carboxylic/amide carbon signals using 2-13Cglucose. Because of the concern over damaging the eye, current carbon-13 MRS has not been applied to studying the frontal lobe. Because the carboxylic/amide carbon signals are coupled to protons via weak long-range coupling only, only a fraction of the RF power is needed for decoupling by the use of noise decoupling. We are implementing the 2-13Cglucose on 3T2 for human studies. Because there is no interference from subcutaneous lipids in the carboxylic/amide region, the method is fully compatible with the multichannel phased-array technology for signal detection while the whole brain is decoupled using noise pulses. Optimization of the 2-13Cglucose method on human subjects using GE 3 Tesla scanners is in progress.? ? The current single-voxel glutamate editing method implemented for 3 Tesla requires several dozen TE averages, therefore making it incompatible with the robust conventional chemical shift imaging. We have developed a new method which only requires a single TE to isolate the glutamate H4 signal. We are currently developing this method for glutamate imaging.? ? Patient movements can cause artifacts in both CSI and GABA editing. The patient movements can be compensated using the signal of the partially suppressed water. Unsuppressed water would be too strong too separate from the metabolite signals, so the sequence is calibrated to suppress water only about a hundredfold. The remaining water signal is still stronger than the metabolite signals and acts as a reference signal to correct for patient motion. The CSI sequence was adapted to make it possible to use the residual water signal as a navigator, the GABA editing sequence did not require changing. Special data processing software was written to correct for phase changes because of patient motion and currently the improvement of the corrections are being quantified.? ? Glutathione is a marker of oxidative stress. We have developed a single voxel proton MRS method for measuring glutathione. Currently we are further optimizing the echo time and investigating methods to minimize interference from nonoverlapping regions.