Measurement of glycine in the human brain in vivo by ¹H-MRS at 3 T: Application in brain tumors

Glycine is a key metabolic intermediate required for the synthesis of proteins, nucleic acids, and other molecules, and its detection in cancer could, therefore, provide biologically relevant information about the growth of the tumor. Here, we report measurement of glycine in human brain and gliomas by an optimized point-resolved spectroscopy sequence at 3 T. Echo time dependence of the major obstacle, myo-inositol (mI) multiplet, was investigated with numerical simulations, incorporating the 3D volume localization. The simulations indicated that a subecho pair (TE₁, TE₂) = (60, 100) ms permits detection of both glycine and mI with optimum selectivity. In vivo validation of the optimized point-resolved spectroscopy was conducted on the right parietal cortex of five healthy volunteers. Metabolite signals estimated from LCModel were normalized with respect to the brain water signal, and the concentrations were evaluated assuming the total creatine concentration at 8 mM. The glycine concentration was estimated as 0.6 ± 0.1 mM (mean ± SD, n = 5), with a mean Cramér-Rao lower bound of 9 ± 1%. The point-resolved spectroscopy sequence was applied to measure the glycine levels in patients with glioblastoma multiforme. Metabolite concentrations were obtained using the water signal from the tumor mass. The study revealed that a subset of human gliomas contains glycine levels elevated 1.5-8 fold relative to normal.