Universal HERMES of GABA and glutathione now includes ethanol

There is currently little understanding of the acute effects of ethanol (EtOH) on the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and the antioxidant glutathione (GSH) levels. Previous MRS studies have demonstrated changes in GABA levels in individuals recovering from alcohol use disorder. Alcohol has also been shown to deplete GSH levels, impeding the elimination of reactive oxygen species.

Sequential MEGA-PRESS measurements of GABA, GSH, and EtOH would necessitate 30-min acquisitions, limiting the number of brain regions investigated within a typical 1-hr MR examination and the time resolution of dynamic studies. Muhammad Saleh and colleagues have extended the universal HERMES editing of GABA and GSH to include orthogonal editing of EtOH without an increase in scan time or substantial loss in spectral quality (see figure below). This new sequence is available collaboratively to the community for application in future studies.

a) The separate Experiments A-D are shown: saturated NAA signal in the ON_GABA spectra; saturated water signal in the ON_GSH spectra; and several signals saturated in the vicinity of 3.67 ppm in the ON_EtOH spectra. The saturation range of the editing pulses is shown on each spectrum as a grayscale. b) The Hadamard combinations yield GABA-edited (A+B–C–D), GSH-edited (A+C–B–D), and EtOH-edited (B+C–A–D) spectra.

Finally! It's here - Universal Edited MRS

MEGA-PRESS, a spectral editing method, has gained popularity in the MRS community thanks to its ability to edit low-concentration metabolites with relative ease of implementation, allowing direct and unambiguous measurements of the inhibitory neurotransmitter GABA, the antioxidant glutathione (GSH), and the anaerobic product lactate (Lac). However, current implementations of MEGA-PRESS are diverse across vendors, differing in terms of RF pulse shapes and pulse sequence timings. Recent multi-site data revealed that ~30% of the variance in the GABA+ data is attributed to the site- and vendor-level differences in the implementation of MEGA-PRESS.

Recently, Muhammad Saleh and colleagues developed a new universal MEGA-PRESS sequence for the major MR vendors (Philips, Siemens, GE, and Canon) with common RF pulse shapes and timings, and has functionality for HERMES editing of GABA and GSH (Figure 1). Upon comparing with the existing vendor-native sequences, the universal sequence yielded edited spectra with strong correlations and low variance among vendors at both short and long TEs phantom and in vivo experiments (Figures 2 and 3). The universal sequence includes simultaneous editing of GABA and GSH with HERMES, allowing excellent separation of the edited signals in half the scan time compared with the sequentially acquired conventional MEGA editing. The universal sequence is available collaboratively to the community for application in future studies.

Exciting times ahead: Building on the universal sequence, Georg Oeltzschner and colleagues developed HERCULES sequence, capable of editing seven coupled metabolites that would usually require a single 11-min editing experiment each. This sequence is also available collaboratively to the community for application in future studies.

For more updates, stay tuned for any new developments from Edden's lab. Universal edited MRS sequences will be presented at the 27th Annual Meeting of the ISMRM, Montreal, Canada, 2019. Looking forward to meeting you all.

Figure 1: Pulse sequence diagrams indicating RF pulse shapes and timings for the vendor-native Philips, Siemens, GE and Canon sequences, and the universal sequence at TE = 68 ms.

Figure 2: a) MEGA-PRESS experiment using the GABA phantom (TE = 68 ms) and Lac phantom (TE = 140 ms) from vendor-native sequences (left) and the universal sequence (right). b) Edited spectra from HERMES experiments acquired using the universal sequence, performed in a GABA phantom (left) and a GSH phantom (right).

Figure 4: In vivo experiments using the universal sequence. Spectra acquired on Philips and Siemens scanners are overlaid for each subject: a) MEGA-PRESS GABA (TE = 68 ms) and Lac (TE = 140 ms) spectra; b) GABA- and GSH-edited HERMES spectra. In vivo experiments using the universal sequence for GE (green) and Canon (red) scanners: c) MEGA-PRESS GABA-edited (TE = 68 ms) and Lac-edited (TE = 140 ms) spectra; d) GABA- and GSH-edited HERMES spectra. Spectra acquired are overlaid on the ± 1SD range (in gray) of the amalgamated Philips and Siemens data (6 subjects).

HERMES hits the road

Exciting times! Postdoctoral fellow Muhammad Saleh is doing his first site visit, setting up HERMES with one of our Siemens collaborator sites.  This sequence, available via C2P agreement, performs MEGA-PRESS (at variable TEs with correct editing pulse spacing), as well as HERMES for GABA/GSH. We are developing sequences with the same RF timings on the other vendor platforms as part of our 'universal editing' project. 

HERMES on Siemens

We are in the late stages of implementing HERMES for GABA/GSH on Siemens.  We are actively seeking collaborators who would like to apply this sequence, so get in touch and we can start the C2P paperwork.

NEW Philips Patch Dissemination for HERMES

We encourage collaborators, currently using our MEGA-PRESS patch to measure GABA, to upgrade to the HERMES patch for future studies.  This patch allows you to measure Glutathione (the most abundant antioxidant in the brain) 'for free', as described in the post below, but also has some useful upgrades to the GABA-only editing. 

We are extremely excited about the HERMES experiment, and expect it to overtake MEGA-PRESS as the most widely used edited experiment.  Drop us an email to request the new patch.