Measuring T2 in vivo with J‐difference editing: Application to GABA at 3 tesla

Proton Magnetic Resonance spectroscopy (1H-MRS) is a useful technique to probe in vivo biochemical status noninvasively, which has been widely applied to study the brain in both clinical and neuroscience settings. If tissue water content is known, metabolite concentrations are often calculated from the relative intensities of metabolite and water signals (1), making appropriate corrections for longitudinal and transverse relaxation (characterized by the time constants T1 and T2, respectively). Thus, the measurement of metabolite relaxation parameters is an important prerequisite for absolute quantification of in vivo MR spectra. In vivo transverse relaxation times (T2) are usually measured by making localized single-voxel measurements at a range of echo times (TE). For singlet resonances, such as N-acetyl aspartate (NAA), creatine (Cr) and choline (Cho), the TE-dependent decay in signal intensity can generally be modeled by a single exponential with time constant T2; metabolite T2s have been measured in this way at a range of field strengths (2–7). The TE-dependence of coupled spin systems is more complicated, because their signals are modulated by both T2 relaxation and scalar coupling evolution. The in vivo T2 of the coupled metabolite glutamate has been measured by modeling the TE dependence of the Glutamate signal (8). However, for many coupled metabolites (such as γ-aminobutyric acid [GABA] (9), glutathione (10), ascorbate (11), and NAAG (12)), low signal amplitude and signal overlap hamper their detection in vivo using conventional MRS methods, and it is usual to use spectral editing methods to detect them reliably. To the best of our knowledge, no method has been published to date that is able to measure the in vivo T2 of metabolites detected using spectral editing techniques. There has been considerable recent interest in MRS measurements of the inhibitory neurotransmitter, GABA, investigating the role of GABA in disease, and the relationships between GABA and functional imaging (13–15) and behavior (16–19). However, although spectral editing methods have been extensively applied to investigate the individual and group differences in GABA levels, they have not been truly quantitative, as human in vivo relaxation parameters for GABA have not been previously measured. Relative measurements of this kind, often quantified in institutional units (i.u.), hamper inferences from separately published studies, both within and between centers. The most common method applied in these studies is J-difference editing (9), often implemented through the MEGA-PRESS technique (20), detecting GABA signals at an intermediate TE (~70 ms). Because this TE is of similar length to typical metabolite T2s (and therefore the anticipated T2 of GABA), measuring the in vivo T2 of GABA is an important step in making these measurements quantitative. It is also known that the “GABA” signal detected at 3.0 ppm using standard J-difference techniques at 3 Tesla (T) contains an appreciable contribution from macromolecules (MM) which has a coupling partner at 1.7 ppm (20). The presence of this MM resonance needs to be accounted for, both for the determination of GABA T2 and for the estimation of “pure” GABA concentrations. In this study, we present a framework for the determination of the in vivo T2 of edited metabolites, that is entirely experimental and does not rely upon simulation, and demonstrate the method to measure the in vivo T2 of GABA at 3T.