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 asym ) at 3 ppm, and oxygen‐weighting was obtained using measurements. Glutamine concentration, pH, and relaxation rates were varied in phantoms to validate simulations and estimate relaxation rates. The values of MTR asym and 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 MTR asym with decreasing pH. The CEST‐SAGE‐EPI estimates of R 2 , , and varied linearly with gadolinium diethylenetriamine penta‐acetic acid concentration (R 2 = 6.2 mM −1 ·sec −1 and = 6.9 mM −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 = 0.9727) were highly correlated. T 2 lesions had lower and higher MTR asym compared with normal‐appearing white matter, suggesting lower hypoxia and high acidity, whereas contrast‐enhancement tumor regions had elevated 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 B 0 correction, and simultaneous estimation of CEST effects, R 2 , , and at 3 T.