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)

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 (MTRasym) at 3 ppm, and oxygen-weighting was obtained using R-2' measurements. Glutamine concentration, pH, and relaxation rates were varied in phantoms to validate simulations and estimate relaxation rates. The values of MTRasym and R-2' in normal-appearing white matter, T-2 hyperintensity, contrast enhancement, and macroscopic necrosis were measured in 47 gliomas. Results: Simulation and phantom results confirmed an increase in MTRasym with decreasing pH. The CEST-SAGE-EPI estimates of R-2, R-2*, and R-2' varied linearly with gadolinium diethylenetriamine penta-acetic acid concentration (R-2 = 6.2mM(-1).sec(-1) and R-2* = 6.9mM(-1).sec(-1)). The CEST-SAGE-EPI and Carr-Purcell-Meiboom-Gill estimates of R-2* (R-2 = 0.9943) and multi-echo gradient-echo estimates of R-2* (R-2 = 0.9727) were highly correlated. T-2 lesions had lower R-2' and higher MTRasym compared with normal-appearing white matter, suggesting lower hypoxia and high acidity, whereas contrast-enhancement tumor regions had elevated R-2'and MTRasym, 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 B-0 correction, and simultaneous estimation of CEST effects, R-2, R-2*, and R-2' at 3 T.