Phase-adjusted echo time (PATE)-averaging ¹H MRS: Application for improved glutamine quantification at 2.89T

¹H MRS investigations have reported altered glutamatergic neurotransmission in a variety of psychiatric disorders. The unraveling of glutamate from glutamine resonances is crucial for the interpretation of these observations, although this remains a challenge at clinical static magnetic field strengths. Glutamate resolution can be improved through an approach known as echo time (TE) averaging, which involves the acquisition and subsequent averaging of multiple TE steps. The process of TE averaging retains the central component of the glutamate methylene multiplet at 2.35ppm, with the simultaneous attenuation of overlapping phase-modulated coupled resonances of glutamine and N-acetylaspartate. We have developed a novel post-processing approach, termed phase-adjusted echo time (PATE) averaging, for the retrieval of glutamine signals from a TE-averaged ¹H MRS dataset. The method works by the application of an optimal TE-specific phase term, which is derived from spectral simulation, prior to averaging over TE space. The simulation procedures and preliminary in vivo spectra acquired from the human frontal lobe at 2.89T are presented. Three metabolite normalization schemes were developed to evaluate the frontal lobe test-retest reliability for glutamine measurement in six subjects, and the resulting values were comparable with previous reports for within-subject (9-14%) and inter-subject (14-20%) measures. Using the acquisition parameters and TE range described, glutamine quantification is possible in approximately 10min. The post-processing methods described can also be applied retrospectively to extract glutamine and glutamate levels from previously acquired TE-averaged ¹H MRS datasets.