Regional and tissue-specific differences in brain glutamate concentration measured by in vivo single voxel MRS

Abstract

Background: There is growing interest in characterizing spatial distribution of glutamate (Glu) in brain disorders. Comparing the differences in Glu concentration using magnetic resonance spectroscopy (MRS) is hampered by the confounding effects of different anatomical regions and tissue composition.

New method: Effect of tissue composition on Glu concentrations was studied by selecting closely adjacent voxels within a designated cortical region. Glu regional differences were assessed using voxels comprising essentially the same tissue composition from different cortical regions.

Results: Using point-resolved-spectroscopy (PRESS)-based averaged echo time method, Glu concentration in the anterior cingulate cortex (ACC) was found to correlate strongly with tissue gray matter (GM) fraction (r=0.87, p=10(-5)). No significant regional difference in Glu concentration was found between frontal and occipital lobes (p=0.23) when the two measured voxels had essentially the same tissue composition.

Comparison with existing methods: The method of the current study is aimed to circumvent the difficulties in differentiating anatomical region from tissue composition, given that both can lead to Glu variations in brain. Glu concentration versus tissue composition was measured in the same anatomical region, while the comparison of regional differences was performed with the two regions that had essentially the same tissue composition.

Conclusions: In brain cortices, Glu level is significantly higher in GM than in WM. Glu level difference between frontal lobe and occipital lobe is insignificant.

Keywords: (1)H MRS; Averaged echo time; Glutamate; Human brain; Metabolite quantification; Regional difference; Tissue composition.

Figure 1

(a): Locations of the two voxels in the median prefrontal cortex (MPFC) and occipital cortex (OCC). (b): locations of the gray matter (GM) voxel (red), the white matter (WM) voxel (yellow), and the mixed voxel (green) in anterior cingulate cortex (ACC).

Figure 2

Representative echo time (TE)-averaged spectra of the median prefrontal cortex (MPFC) (a) and occipital cortex (OCC) (b). Fitted spectra are displayed in red. Top and bottom traces are fit residuals and baselines, respectively.

Figure 3

Representative echo time (TE)-averaged spectra with different compositions of gray matter (GM) and white matter (WM) in the anterior cingulate cortex (ACC). GM fractions were 0.62, 0.41, and 0.26, corresponding to (a), (b), and (c), respectively. The spectral data were acquired from the same subject. Fitted spectra are displayed in red. Top and bottom traces are fit residuals and baselines, respectively.

Figure 4

Pearson’s correlations of metabolite concentrations versus fractions of gray matter (GM) in the anterior cingulate cortex (ACC). Data of individual subjects are labeled by square, triangle, plus sign, times sign, and rhombus, respectively.