In vivo assessment of neurotransmitters and modulators with magnetic resonance spectroscopy: application to schizophrenia

Abstract

In vivo measurement of neurotransmitters and modulators is now feasible with advanced proton magnetic resonance spectroscopy ((1)H MRS) techniques. This review provides a basic tutorial of MRS, describes the methods available to measure brain glutamate, glutamine, γ-aminobutyric acid, glutathione, N-acetylaspartylglutamate, glycine, and serine at magnetic field strengths of 3T or higher, and summarizes the neurochemical findings in schizophrenia. Overall, (1)H MRS holds great promise for producing biomarkers that can serve as treatment targets, prediction of disease onset, or illness exacerbation in schizophrenia and other brain diseases.

Keywords: GABA; Glutamate; Glutathione; Magnetic resonance spectroscopy; Schizophrenia.

Figure 1

T₁-weighted voxel images acquired at 3T with a MP-RAGE imaging sequence (TR/TE/TI=1900/3.45/900-ms, FOV 256 × 256 mm, 1-mm isotropic voxels, flip angle = 9°). These images show that the voxel was placed in the anterior cingulate (a). A very short echo time (TE) spectrum with corresponding plots of each metabolite in the spectrum shown below (b). These metabolites are included in the basis set used for quantification. The metabolites were simulated at a frequency of 123.56-MHz using a STEAM sequence (TR/TM/TE=2000/10/6.5ms).

Figure 1

T₁-weighted voxel images acquired at 3T with a MP-RAGE imaging sequence (TR/TE/TI=1900/3.45/900-ms, FOV 256 × 256 mm, 1-mm isotropic voxels, flip angle = 9°). These images show that the voxel was placed in the anterior cingulate (a). A very short echo time (TE) spectrum with corresponding plots of each metabolite in the spectrum shown below (b). These metabolites are included in the basis set used for quantification. The metabolites were simulated at a frequency of 123.56-MHz using a STEAM sequence (TR/TM/TE=2000/10/6.5ms).

Figure 2

The macromolecule background is only present at shorter TEs due to its short T₂ constituents, and it can be a complicating factor in quantification. This is an example short TE spectrum (black) with its macromolecule background fit spectrum shown underneath (gray) as fit by LCModel. These data were acquired at 3T using a very short TE phase rotation sequence (TR/TM/TE=2000/10/6.5-ms, 256 excitations, 2.5-kHz spectral width, 2048 complex points, and phases: ϕ₁=135°, ϕ₂=22.5°, ϕ₁₃=112.5°, ϕ_ADC=0°).