The goal of this research is to develop advanced magnetic resonance spectroscopy (MRS) and imaging techniques and to apply them and other complementary methods to studying brain metabolism, neurotransmission and enzyme activity. MRS allows measurement of the neurotransmission of glutamate and GABA in vivo, which plays important roles in many major psychiatric diseases, including depression and schizophrenia. During 2016-2017, we made significant progress in the development and application of novel spectroscopic and imaging techniques for studying metabolism and neurotransmission in vivo in the brain. We invented and validated a computational method for quantifying spatially localized MRS data involving multiple nuclear spin systems (Zhang et al, Med. Phys., 2017, doi: 10.1002/mp.12375). This method can reduce the time for calculating chemical basis function, using a typical desktop personal computer, from days and weeks to just a few minutes. As such, design and optimization of proton MRS by computers have become practical and highly useful. By optimizing localized proton MRS using extensive computation to simultaneously maximize spectral resolution and sensitivity to nuclear spin relaxation we have developed a novel multiparametric technique that can simultaneously measure concentration, longitudinal and transverse relaxation times of many brain chemicals, including glutamate, in a single scan session within ten minutes of MRS data acquisition. This multiparametric approach allows us to measure both concentrations and the microenvironments of brain chemicals (e.g., glutamatergic neurons) in a typical clinical setting (An et al, Magn Reson Med. 2017. doi: 10.1002/mrm.26612.). In addition, a novel radiofrequency pulse-driven steady state method has been developed that can measure transverse relaxation of chemicals without the need to change echo times. Significant progress has also been made in studying glutamate and GABA neurotransmission and in vivo enzyme activities in both human and animal experiments. In particular, we demonstrated, for the first time, the feasibility of measuring carbonic anhydrase activity in the human subjects.
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