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 (MTR ) 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 and R2' in normal-appearing white matter, T hyperintensity, contrast enhancement, and macroscopic necrosis were measured in 47 gliomas.

RESULTS

Simulation and phantom results confirmed an increase in MTR with decreasing pH. The CEST-SAGE-EPI estimates of R , R2*, and R2' varied linearly with gadolinium diethylenetriamine penta-acetic acid concentration (R  = 6.2 mM ·sec and R2* = 6.9 mM ·sec ). The CEST-SAGE-EPI and Carr-Purcell-Meiboom-Gill estimates of R (R  = 0.9943) and multi-echo gradient-echo estimates of R2* (R  = 0.9727) were highly correlated. T lesions had lower R2' and higher MTR compared with normal-appearing white matter, suggesting lower hypoxia and high acidity, whereas contrast-enhancement tumor regions had elevated R2' and MTR , 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 correction, and simultaneous estimation of CEST effects, R , R2*, and R2' at 3 T.