Elsevier

NeuroImage

Volume 30, Issue 4, 1 May 2006, Pages 1171-1178
NeuroImage

TE-Averaged two-dimensional proton spectroscopic imaging of glutamate at 3 T

https://doi.org/10.1016/j.neuroimage.2005.10.048Get rights and content

Abstract

Glutamate and glutamine are important neurochemicals in the central nervous system and the neurotoxic properties of excess glutamate have been associated with several neurodegenerative diseases. The TE-Averaged PRESS technique has been shown by our group to detect an unobstructed glutamate signal at 3 T that is resolved from glutamine and NAA at 2.35 ppm. TE-Averaged PRESS therefore provides an unambiguous measurement of glutamate as well as other metabolites such as NAA, choline, creatine, and myo-inositol. In this study, we extend the single voxel TE-Averaged PRESS technique for two-dimensional (2D) spectroscopic imaging (TE-Averaged MRSI) to generate 2D glutamate maps. To facilitate TE-Averaged MRSI within a reasonable time, a fast encoding trajectory was used. This enabled rapid acquisition of TE-Averaged spectral arrays with good spectral bandwidth (977 Hz) and resolution (∼2 Hz). MRSI data arrays of 10 × 16 were acquired with 1.8 cm3 spatial resolution over a ∼110 cm3 volume in a scan time of ∼21 min. Two-dimensional metabolite maps were obtained with good SNR and clear differentiation in glutamate levels was observed between gray and white matter with significantly higher glutamate in gray matter relative to white matter as anticipated.

Introduction

Glutamate and glutamine are important neurotransmitters in the central nervous system. The neurotoxic properties of excess glutamate have been associated with several neurodegenerative diseases. Glutamate and glutamine are strongly coupled systems and resonate at multiple frequencies. Due to similar chemical components, these metabolites overlap significantly in the 1H resonance spectrum. Higher magnetic field strength offers a possibility of resolving glutamate and glutamine resonances due to larger frequency dispersion and simplification of J coupling patterns (Mason et al., 1994). J-refocused coherence transfer methodology has also been used for the spectroscopic imaging of glutamate at 4.1 T using 1H (Pan et al., 1996) and 13C spectroscopy (Pan et al., 1997).

At 3 T, it is challenging to measure glutamate and glutamine separately using conventional one-dimensional spectroscopic methodologies. Techniques such as chemical shift selective filter (Schulte et al., 2005), 2D constant time PRESS (CT-PRESS) (Mayer and Spielman, 2005), and 2D J-resolved (Thomas et al., 1996) spectroscopy have been developed to increase the spectral resolution of strongly coupled metabolites by the measurement of an additional spectral dimension—also known as the J-resolved dimension. Recently, we have shown (Hurd et al., 2004) that the zeroth component of a 2D J-resolved spectrum resulted in an unobstructed detection of glutamate at 2.35 ppm that was distinct from glutamine and NAA. This technique called TE-Averaged PRESS has been implemented as a single voxel technique and was used to show differences in glutamate levels between normal subjects and Multiple Sclerosis patients (Srinivasan et al., 2005). While TE-Averaged PRESS results in a unobstructed glutamate detection, it does not differentiate between intra- and extra-cellular glutamate.

Due to the additional time required for the acquisition of a second spectral dimension to isolate the glutamate resonance, spatially resolved, two-dimensional spectral acquisitions involve prohibitive scan times when conventional phase encode methods are used. To incorporate J-resolved techniques for spectroscopic imaging, rapid acquisitions using time varying gradients during the readout window have been used (Adalsteinsson and Spielman, 1999), which encode some of the spatial information simultaneously with the spectral readout.

In this study, we developed a spectroscopic imaging technique (TE-Averaged MRSI) by combining TE-Averaged PRESS scheme for the measurement of an unobstructed glutamate resonance with fast spectroscopic imaging to obtain glutamate estimates over a 2D region of interest within a clinically reasonable time. To speed up the data acquisition for TE-Averaged MRSI, we used the flyback echo planar gradient trajectory (Mulkern and Panych, 2001, Feinberg et al., 1990) that was recently optimized for 3 T MRSI studies by our group (Cunningham et al., 2005). Use of this fast trajectory to simultaneously encode 16 spatial encode steps and the spectral dimension makes the scan time for a two-dimensional (10 × 16) TE-Averaged MRSI acquisition equivalent to a one-dimensional acquisition resulting in a dramatic reduction in scan time making J-resolved acquisitions feasible within a clinically acceptable time.

Section snippets

Materials and methods

All data were acquired on a 3 T GE SIGNA scanner on an EXCITE platform using an 8-channel phased array coil with body coil transmit.

Results

Fig. 1 shows spectra from a subset of MRSI voxels from TE-Averaged MRSI data obtained from phantoms that contained one metabolite and their relationship to an in-vivo spectrum. As observed, the TE-Averaged MRSI acquisition scheme preserves unobstructed detection of glutamate signal at 2.35 ppm as our previous single voxel implementation. In vivo TE-Averaged MRSI data were obtained with good quality and SNR (Fig. 2) over the entire spectral array with a well detected glutamate peak. The SNR for

Discussion

The main goal of this study was to provide a clinically feasible technique at 3 T for the detection of glutamate over a two-dimensional region using a spectroscopic editing method called TE-Averaged PRESS which has been shown by our group to provide an unobstructed detection of glutamate in single voxel studies. Compared to single voxel 1H MRS, multi-voxel proton magnetic resonance spectroscopy imaging (1H MRSI) increases spatial coverage and offers clear advantages for application to

Conclusion

This study has demonstrated the successful implementation of the TE-Averaged MRSI scheme for detection of unobstructed glutamate within a 2D region of interest with good SNR and spatial resolution. Significantly higher glutamate levels were obtained in GM relative to WM, validating our acquisition and quantification methodologies. Use of a fast spectroscopic imaging technique resulted in a significant reduction in scan time (∼21 min) making TE-Averaged MRSI a viable technique for brain

Acknowledgments

The authors would like to thank Dr. Napapon Sailasuta for helpful discussions. Work was supported as part of the University of California Industry-University Cooperative Research Program (LSIT01-10107) and National Multiple Sclerosis Society (RG3517A2, PI. Daniel Pelletier).

References (25)

  • E. Adalsteinsson et al.

    Spatially resolved two-dimensional spectroscopy

    Magn. Reson. Med.

    (1999)
  • P. Barker et al.

    Single-voxel proton MRS of the human brain at 1.5 T and 3.0 T

    Magn. Reson. Med.

    (2001)
  • M.A. Brown

    Time-domain combination of MR spectroscopy data acquired using phased-array coils

    Magn. Reson. Med.

    (2004)
  • C.H. Cunningham et al.

    Design of flyback echo-planar readout gradients for MR spectroscopic imaging

    Proc. ISMRM

    (2005)
  • T. Ethofer et al.

    Comparison of longitudinal metabolite relaxation times in different regions of the human brain at 1.5 and 3 Tesla

    Magn. Reson. Med.

    (2003)
  • D.A. Feinberg et al.

    Echo-planar imaging with asymmetric gradient modulation and inner-volume excitation

    Magn. Reson. Med.

    (1990)
  • I. Hancu et al.

    Automatic repositioning of single voxels in longitudinal 1H MRS studies

    NMR Biomed.

    (2005)
  • H.P. Hetherington et al.

    Quantitative 1H spectroscopic imaging of human brain at 4.1T using image segmentation

    Magn. Reson. Med.

    (1996)
  • R. Hurd et al.

    Measurement of brain glutamate using TE-Averaged PRESS at 3T

    Magn. Reson. Med.

    (2004)
  • Lee, M.C., Cha, S., Chang, S.M., Nelson, S.J., in press. Determination of normal tissue white matter and gray matter...
  • G.F. Mason et al.

    Detection of brain glutamate and glutamine in spectroscopic images at 4.1 T

    Magn. Reson. Med.

    (1994)
  • D. Mayer et al.

    Detection of glutamate in the human brain at 3T using optimized constant time point resolved spectroscopy

    Magn. Reson. Med.

    (2005)
  • Cited by (63)

    • Magnetic resonance markers of tissue damage related to connectivity disruption in multiple sclerosis

      2018, NeuroImage: Clinical
      Citation Excerpt :

      SIENAX (https://fsl.fmrib.ox.ac.uk/fsl/fslwiki/SIENA), performed after lesion filling, was used to obtain WM and GM maps in order to measure the percentage of their content within each spectroscopic voxel. Then, the metabolic estimates for each tissue type were extrapolated from the endpoints of linear regression models in R Software (https://www.r-project.org/) as previously described (Azevedo et al., 2014; Srinivasan et al., 2006) (Fig. 2). Metabolic outliers from each group of participants were removed from the regression models.

    • Region-specific aging of the human brain as evidenced by neurochemical profiles measured noninvasively in the posterior cingulate cortex and the occipital lobe using <sup>1</sup>H magnetic resonance spectroscopy at 7 T

      2017, Neuroscience
      Citation Excerpt :

      In both voxels, the percentage of GM decreased and the percentage of WM increased with age. If known concentrations of the five commonly observed neurochemicals in GM and WM (Adany et al., 2016) are consulted, the changes in concentrations due only to difference in VOI composition would be relatively small (1–4%) for all except Glu, which has been reported to have two times higher concentration in GM than WM (Srinivasan et al., 2006). Except tCho, the expected outcome would be decrease in the metabolite concentration.

    View all citing articles on Scopus
    View full text