Glycine as a Biomarker in Brain Tumors

Glycine is a major inhibitory neurotransmitter in the mammalian central nervous system. High levels of glycine have been detected in the brain of patients with hyperglycinemia and in brain tumors in particular glioblastoma multiforme (GBM). Given its significance, an accurate measure of brain glycine is desirable; this is hindered by the fact that its resonance overlaps with the resonances of myo-inositol. Because of myo-inositol’s short TE, glycine can be detected in long TE and when editing, TE-averaged point resolved spectroscopy (PRESS) or 2D J-PRESS are used. Here we employed HRMAS 1H MRS to quantify glycine (Gly) in brain tumor biopsies using the Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence. We show that reliable detection of Gly in brain tumor biopsies is feasible using HRMAS 1H MRS at TE of 50 ms with CPMG. With respect to the choice of TE, this is a TE at which the amplitude of the Myo resonance is sufficiently reduced to allow for Gly detection. The Gly resonance, being a singlet at 3.55 ppm that is overlapped by the more intense Myo resonances, cannot be directly edited, but requires approaches that minimize the signal contribution from Myo. Our results show that we can differentiate brain tumor types based on the amount of Gly they contain and are in agreement with prior observations. Especially the distinction between high-grade tumors (i.e., GBM) and metastasis is of clinical significance because it is a distinction not made adequately at present. Here, it is the reduced Myo and high glycine that distinguish GBM from MT, which exhibit both Myo and Gly resonances. We propose Gly as a useful biomarker in brain tumors.