Absolute Quantitation of Glutamate, GABA and Glutamine using Localized 2D Constant-time COSY Spectroscopy in Vivo

Abstract

We propose an absolute quantitation method for metabolites with strongly coupled spin systems using localized 2-dimensional (2D) constant-time correlation spectroscopy (CT-COSY). We also develop two methods for improving the quality of in vivo CT-COSY spectra. We substituted an image selected in vivo spectroscopy (ISIS) pulse for a 180° slice pulse in the CT-COSY module to decrease the slice displacement error caused by the chemical shift difference. We measured the slice displacement error due to the differences in the carrier frequency of slice pulse in a phantom experiment to demonstrate this feature. We also developed an asymmetric sampling scheme along the t1 direction to resolve diagonal peaks even in the magnitude mode of 2D spectra. We collected CT-COSY signals of a human brain for a 14% asymmetric sampling scheme. After reconstruction, we obtained a 2D CT-COSY spectrum in magnitude mode and compared a peak of glutamate (Glu) C4H on that spectrum to a peak displayed in absorption mode. In our proposed absolute quantitation method, we developed T2 correction, curve-fitting for computing peak volume and calibration by an internal water reference. We used the method to measure the Glu concentration in 10-mM glutamate phantom experiments. We also attempted to measure concentrations of Glu, γ-aminobutyric acid (GABA) and glutamine (Gln) in a human brain. Slice displacement error was decreased by a factor of 2.5 using the proposed sequence. Spectra with narrow linewidths could be obtained using the asymmetric sampling scheme in the magnitude mode. Measured Glu concentration in the solution phantom was 9.4 mM. Concentrations of Glu (9.5 mM), GABA (0.61 mM) and Gln (3.6 mM) in a human brain measured by our method agreed well with previously reported values. Concentrations of metabolites with strongly coupled spin systems can be measured using our proposed absolute quantitation method on 2D CT-COSY spectra.