Simultaneous pH-sensitive and oxygen-sensitive MRI of human gliomas at 3 T using multi-echo amine proton chemical exchange saturation transfer spin-and-gradient echo echo-planar imaging (CEST-SAGE-EPI)

Abstract

Purpose: To introduce a new pH-sensitive and oxygen-sensitive MRI technique using amine proton CEST echo spin-and-gradient echo (SAGE) EPI (CEST-SAGE-EPI).

Methods: pH-weighting was obtained using CEST estimations of magnetization transfer ratio asymmetry (MTR_asym ) at 3 ppm, and oxygen-weighting was obtained using R2' measurements. Glutamine concentration, pH, and relaxation rates were varied in phantoms to validate simulations and estimate relaxation rates. The values of MTR_asym and R2' in normal-appearing white matter, T₂ hyperintensity, contrast enhancement, and macroscopic necrosis were measured in 47 gliomas.

Results: Simulation and phantom results confirmed an increase in MTR_asym with decreasing pH. The CEST-SAGE-EPI estimates of R₂ , R2*, and R2' varied linearly with gadolinium diethylenetriamine penta-acetic acid concentration (R₂ = 6.2 mM^-1 ·sec^-1 and R2* = 6.9 mM^-1 ·sec^-1 ). The CEST-SAGE-EPI and Carr-Purcell-Meiboom-Gill estimates of R₂ (R² = 0.9943) and multi-echo gradient-echo estimates of R2* (R₂ = 0.9727) were highly correlated. T₂ lesions had lower R2' and higher MTR_asym compared with normal-appearing white matter, suggesting lower hypoxia and high acidity, whereas contrast-enhancement tumor regions had elevated R2' and MTR_asym , indicating high hypoxia and acidity.

Conclusion: The CEST-SAGE-EPI technique provides simultaneous pH-sensitive and oxygen-sensitive image contrasts for evaluation of the brain tumor microenvironment. Advantages include fast whole-brain acquisition, in-line B₀ correction, and simultaneous estimation of CEST effects, R₂ , R2*, and R2' at 3 T.

Keywords: CEST; SAGE; glioma; hypoxia; pH-weighted MRI.