Edited 1 H magnetic resonance spectroscopy in vivo: Methods and metabolites

Abstract

The Proton magnetic resonance (¹ H-MRS) spectrum contains information about the concentration of tissue metabolites within a predefined region of interest (a voxel). The conventional spectrum in some cases obscures information about less abundant metabolites due to limited separation and complex splitting of the metabolite peaks. One method to detect these metabolites is to reduce the complexity of the spectrum using editing. This review provides an overview of the one-dimensional editing methods available to interrogate these obscured metabolite peaks. These methods include sequence optimizations, echo-time averaging, J-difference editing methods (single BASING, dual BASING, and MEGA-PRESS), constant-time PRESS, and multiple quantum filtering. It then provides an overview of the brain metabolites whose detection can benefit from one or more of these editing approaches, including ascorbic acid, γ-aminobutyric acid, lactate, aspartate, N-acetyl aspartyl glutamate, 2-hydroxyglutarate, glutathione, glutamate, glycine, and serine. Magn Reson Med 77:1377-1389, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Keywords: J-coupling; J-difference editing; constant-time PRESS; echo-time averaging; magnetic resonance spectroscopy (MRS); metabolites; quantum filtering.

Figure 1

Pulse sequences that are used to edit the spectrum. A. TE-averaging: the echo time is varied during the acquisition. The typical PRESS localization scheme is used with gradients applied during the 90 excitation pulse and the two 180 refocussing pulses. B. Single BASING: a single frequency-selective editing pulse is placed between the two refocusing pulses. C. Dual Basing: in half of the transients, two frequency-selective editing pulses are applied, one after each refocusing pulse. These editing pulses refocus the evolution of selected couplings. In the remaining half of the transients, these pulses are not applied (pulse sequence not shown) such that in the subtraction spectrum, overlapping larger resonances are removed, revealing only the spins impacted by the editing pulses. D. MEGA (MEscher-GArwood): Similar to the dual BASING scheme, a pair of frequency-selective editing pulses refocus the evolution of the coupling in half of the transients, the ‘On’ condition. The difference between the subspectra with and without the refocusing pulses subtracts the overlapping metabolites to reveal the metabolite of interest. E. Asymmetric PRESS: Two spectra with same TE but different interpulse delays are acquired. Timings are optimized to maximize differences in the modulation of strongly coupled spins, so their signals are enhanced in the difference spectrum, and resonances from singlets are removed. F. Example of a double quantum filter experiment and the associated coherence transfer pathway. The double-quantum coherence is formed by the excitation pulse, first refocusing pulse and an additional 90° pulse. Subsequently, the 90° frequency-selective pulses convert the desired double quantum signals into observable coherence. G. Polarization transfer: First, signals in the spectral range of interest are pre-saturated (PRESAT). Signal is then excited on a spin outside the saturated range and transfered to a coupled partner. Within the saturated range, only signal that arises from such coherence transfer give detectable signals in the acquired spectrum. Coherence transfer is achieved by the pulse marked 90°.

Figure 2

Simulation of TE-averaged data for glutamate. A. Simulated glutamate spec- trum at various TEs ranging from 35 ms to 355 ms. Notice the multiplet structure changes with incrementing TE. B. Simulation of the TE-averaged spectrum from glutamate, using a minimum TE = 35 ms, incrementing in steps of 10 ms up to TE = 355 ms. In the TE-averaged spectrum, the peaks are simplified as the outer wings are effectively cancelled. Spectra were simulated using FID-A (115).

Figure 3

The appearance of the detected peaks in the On, Off and Diff spectra of (A) a doublet (e.g., lactate) and (B) a triplet (e.g., approximately GABA) for J-difference editing.

Figure 4

Example (A) On, (B) Off and (C) difference spectra for a GABA-edited experiment. In the On subspectrum, a frequency-selective editing pulse is applied, in this case a 1.9 ppm. In the Off subspectrum, no editing pulse is applied so in the Diff spectrum the overlapping creatine peak is removed. The frequency-selective editing pulse (On sub-spectrum) co-edits MM and Glx. The co-edited MM peak is also at 3 ppm, hence the term GABA+. The co-edited Glx peak is seen at 3.75 ppm.

Figure 5

Schematic to illustrate the classes of co-editing. A. Non-overlapping co-editing: the editing pulse modulates two metabolites that have coupled spins at different chemical shifts. B. DEW: the On sub-spectrum for metabolite-1 serves as the Off subspectrum for metabolite 2 and vice versa. C. HERMES: the detected signals have similar chemical shift but can still be resolved using Hadamard-encoded editing as the editing targets spins are at different chemical shifts.

Figure 6

Chemical structures and coupling constants of metabolites that can be measured using edited MRS methods. Asc: ascorbic acid, NAA: N-acetyl aspartate, GABA: γ-aminobutyric acid, Lac: lactate, Asp: aspartate, NAAG: N-acetyl aspartyl glutamate, 2HG: 2-hydroxyglutarate, GSH: glutathione, Glu: glutamate, Gly: glycine, Ser: serine.