A Potential Magnetic Resonance Imaging Technique Based on Chemical Exchange Saturation Transfer for In Vivo γ-Aminobutyric Acid Imaging

Gen Yan,Gang Xiao,Yanlong Jia,Zhuozhi Dai,Handi Zhang,Renhua Wu,Meizhi Yi,Tingting Nie,Tao Zhang,Quan Jiang

doi:10.1371/journal.pone.0163765

Abstract

PurposeWe developed a novel magnetic resonance imaging (MRI) technique based on chemical exchange saturation transfer (CEST) for GABA imaging and investigated the concentration-dependent CEST effect ofGABA in a rat model of brain tumor with blood—brain barrier (BBB) disruption.Materials and MethodsAll MRI studies were performed using a 7.0-T Agilent MRI scanner. Z-spectra for GABA were acquired at 7.0 T, 37°C, and a pH of 7.0 using varying B1 amplitudes. CEST images of phantoms with different concentrations of GABA solutions (pH, 7.0) and other metabolites (glutamine, myoinositol, creatinine, and choline) were collected to investigate the concentration-dependent CEST effect of GABA and the potential contribution from other brain metabolites. CEST maps for GABA in rat brains with tumors were collected at baseline and 50 min, 1.5 h, and 2.0 h after the injection of GABA solution.ResultsThe CEST effect of GABA was observed at approximately 2.75 parts per million(ppm) downfield from bulk water, and this effect increased with an increase in the B1 amplitude and remained steady after the B1 amplitude reached 6.0 μT (255 Hz). The CEST effect of GABA was proportional to the GABA concentration in vitro. CEST imaging of GABA in a rat brain with a tumor and compromised BBB showed a gradual increase in the CEST effect after GABA injection.ConclusionThe findings of this study demonstrate the feasibility and potential of CEST MRI with the optimal B1 amplitude, which exhibits excellent spatial and temporal resolutions, to map changes in GABA.

Highlights

The findings of this study demonstrate the feasibility and potential of chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) with the optimal B1 amplitude, which exhibits excellent spatial and temporal resolutions, to map changes in GABA
By subtraction of two images collected with a saturation frequency selected at ±2.75 ppm, we obtained the CEST images of GABA for a phantom comprising test tubes with different concentrations of GABA solutions immersed in a beaker containing phosphatebuffered saline (PBS) (Fig 2a)
To investigate the concentration-dependent CEST effect of GABA in vivo, we built a tumor model with a compromised blood—brain barrier (BBB), and CEST maps gathered at baseline and 50 min, 1.5 h, and 2.0 h after intravenous injection of GABA showed a gradual increase in the CEST signal of GABA in the tumor (Fig 4)

Summary

Materials and Methods

All MRI studies were performed using a 7.0-T Agilent MRI scanner. Z-spectra for GABA were acquired at 7.0 T, 37 ̊C, and a pH of 7.0 using varying B1 amplitudes. CEST images of phantoms with different concentrations of GABA solutions (pH, 7.0) and other metabolites (glutamine, myoinositol, creatinine, and choline) were collected to investigate the concentration-dependent CEST effect of GABA and the potential contribution from other brain metabolites. CEST maps for GABA in rat brains with tumors were collected at baseline and 50 min, 1.5 h, and 2.0 h after the injection of GABA solution

Results

Conclusion

Discussion