Simultaneous edited MR spectroscopy of glutathione and macromolecule-suppressed GABA

Stand-By Time

Thursday, June 29, 2017: 12:45 PM - 2:45 PM

Submission No:

3577 

Submission Type:

Abstract Submission 

On Display:

Wednesday, June 28 & Thursday, June 29 

Authors:

Georg Oeltzschner1,2, Kimberly Chan1,2,3, Muhammad Saleh1,2, Nicolaas Puts1,2, Mark Mikkelsen1,2, Richard Edden1,2

Institutions:

1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, 2F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, 3Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD

First Author:

Georg Oeltzschner    -  Lecture Information | Contact Me
Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University|F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute
Baltimore, MD|Baltimore, MD

Introduction:

Levels of the main inhibitory neurotransmitter γ-aminobutyric acid (GABA) and the main antioxidant glutathione (GSH) can be altered in a range of neuropsychiatric disorders, indicating inhibitory and/or redox dysfunction (1,2). Both compounds can be quantified in vivo with J-difference edited MR spectroscopy (MRS), but time-consuming acquisition (~10 min per metabolite per region) limits the number of measurements a research protocol can accommodate. Conventional editing of GABA further suffers from co-editing of macromolecular resonances (MM) (usually reported as 'GABA+'), which can be avoided by arranging the editing pulses symmetrically about the 1.7 ppm MM resonance (3).
Recently, Hadamard encoding and reconstruction of MEGA-edited spectroscopy (HERMES) has been presented for simultaneous spectral editing of two compounds, such as NAA/NAAG (4) and GABA+/GSH (5). HERMES halves scan time while maintaining spectral quality and signal-to-noise ratio.
Here, we introduce macromolecule-suppressed (MMs) HERMES for simultaneous spectral-edited measurement of GSH and GABA without MM contamination.

Methods:

MMs-HERMES consists of four sub-experiments with different editing targets (Fig. 1a): (A) dualband pulse (4.56 ppm & 1.9 ppm); (B) dualband pulse (4.56 ppm & 1.5 ppm); (C) single-band pulse (1.9 ppm); (D) single-band pulse (1.5 ppm). The combination A+B-C-D yields a GSH-edited difference spectrum, while the combination A+C-B-D results in a macromolecule-suppressed GABA-edited difference spectrum. Both Hadamard subtractions are balanced with respect to MM signals, so no MM signal appears in the resulting spectra.
Simulations: Bloch simulations were performed with FID-A (6) to determine the inversion profiles for the four sub-experiments.
In vivo: 10 healthy subjects (6 male, age 31.3 ± 8.3 y) were recruited under local IRB approval. MRS data were acquired with a 32-channel phased-array head coil on a Philips 'Achieva' scanner at 3T field strength from a (3.3 cm)3 midline parietal voxel (Fig. 1b) with the following common parameters: TR/TE = 2000/80 ms, 20-ms editing pulses (FWHM 61.9 Hz), prospective frequency correction (7) with 1 water-unsuppressed acquisition per 8 water-suppressed transients. MMs-HERMES (320 averages), and two separate GSH-edited and GABA-edited MEGA-PRESS experiments with the same total duration (160 averages each) were acquired.
Data were processed using Gannet (8), including frequency-and-phase correction (Spectral Registration (9) for GABA data, choline-based alignment for GSH data). The 3 ppm GABA resonance was fit with a single Gaussian model. The 2.95 ppm GSH resonance and adjacent aspartyl resonances were fit with a five-Gaussian model.
Supporting Image: Fig1.png
   ·Figure 1: (a) Bloch simulations of the editing pulse inversion profiles in the four MMs-HERMES sub-experiments. (b) Exemplary in vivo voxel placement in the midline parietal area of the brain.
 

Results:

Simulations of the dual-lobe inversion profiles revealed no significant offset to their single-lobe equivalents (<1 Hz), showing that the frequency accuracy requirements of symmetric editing (7) are met.
MMs-HERMES (orange) and MEGA-PRESS (blue) spectra are overlaid in Fig. 2, showing good agreement between experiments. Mean GABA (GSH) estimates were 0.93 ± 0.14 i.u. (0.57 ± 0.19 i.u.) for MMs-HERMES, and 0.96 ± 0.07 i.u. (0.74 ± 0.15 i.u.) for MEGA-PRESS. Mean GABA (GSH) differences between MMs-HERMES and MEGA-PRESS were -0.03 ± 0.10 i.u. (-0.17 ± 0.13 i.u.). Mean SNR improvement of MMs-HERMES compared to MEGA-PRESS was 1.44 ± 0.25 (close to the expected √2).
Deviations between the two methods may arise from spectral alignment, and variable baseline near the GSH peak. The NAA and residual water peaks - both markedly important for frequency-and-phase correction - are differentially affected in the HERMES sub-experiments. Advanced alignment routines for multiplexed experiments are expected to improve results, as is progress in GSH fitting.
Supporting Image: Fig2.png
   ·Figure 2: MMs-HERMES (orange) and conventional MEGA-PRESS (blue) spectra of all 10 healthy subjects. Left column: MM-suppressed GABA-edited spectra; right column: GSH-edited spectra.
 

Conclusions:

MMs-HERMES allows simultaneous editing of GSH and GABA, effectively halving scan time compared to conventional MEGA-PRESS experiments. HERMES is compatible with symmetrical suppression of co-edited MM signals.

Imaging Methods:

MR Spectroscopy 1

Physiology, Metabolism and Neurotransmission :

Physiology, Metabolism and Neurotransmission Other 2

Keywords:

Acquisition
Data analysis
Experimental Design
GABA
Magnetic Resonance Spectroscopy (MRS)
MR SPECTROSCOPY
MRI
MRI PHYSICS
Neurotransmitter
Psychiatric Disorders

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Please indicate below if your study was a "resting state" or "task-activation” study.

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Healthy subjects

Internal Review Board (IRB) or Animal Use and Care Committee (AUCC) Approval. Please indicate approval below. Please note: Failure to have IRB or AUCC approval, if applicable will lead to automatic rejection of abstract.

Yes, I have IRB or AUCC approval

Please indicate which methods were used in your research:

Other, Please specify  -   MR spectroscopy

For human MRI, what field strength scanner do you use?

3.0T

Which processing packages did you use for your study?

Other, Please list  -   Gannet

Provide references in author date format

1. Puts NAJ (2012), In vivo magnetic resonance spectroscopy of GABA: A methodological review. Progress in Nuclear Magnetic Resonance Spectroscopy, 60:29–41.
2. Terpstra M (2006), Detection of an antioxidant profile in the human brain in vivo via double editing with MEGA-PRESS. Magnetic Resonance in Medicine, 56:1192–1199.
3. Henry P-G (2001), Brain GABA editing without macromolecule contamination. Magnetic Resonance in Medicine, 45:517–520.
4. Chan KL (2016), HERMES: Hadamard encoding and reconstruction of MEGA-edited spectroscopy, Magnetic Resonance in Medicine, 76:11–19.
5. Saleh MG (2016), Simultaneous edited MRS of GABA and glutathione, NeuroImage (in press), doi: 10.1016/j.neuroimage.2016.07.056.
6. Simpson R (2015), Advanced processing and simulation of MRS data using the FID appliance (FID‐A) - An open source, MATLAB‐based toolkit, Magnetic Resonance in Medicine (in press), doi: 10.1002/mrm.26091.
7. Edden RAE (2016), Prospective frequency correction for macromolecule-suppressed GABA editing at 3T, Journal of Magnetic Resonance Imaging (in press), doi: 10.1002/jmri.25304.
8. Edden RAE (2014), Gannet: A batch-processing tool for the quantitative analysis of gamma-aminobutyric acid–edited MR spectroscopy spectra, Journal of Magnetic Resonance Imaging, 40:1445–1452.
9. Near J (2015), Frequency and phase drift correction of magnetic resonance spectroscopy data by spectral registration in the time domain, Magnetic Resonance in Medicine, 73:44–50.