The pH sensitivity of APT‐CEST using phosphorus spectroscopy as a reference method

The pH value is a potential physiological marker for clinical diagnosis as it is altered in pathologies such as tumors. While intracellular pH can be measured noninvasively via phosphorus spectroscopy (³¹P MRSI), Amide Proton Transfer‐Chemical Exchange Saturation Transfer (APT‐CEST) MRI has been suggested as an alternative method for pH quantification. To assess the suitability of APT‐CEST contrast for pH quantification, two approaches (magnetization transfer ratio asymmetry [MTR_asym] and Lorentzian difference analysis [LDA]) for analyzing the Z‐spectrum have been correlated with pH values obtained by ³¹P MRSI. Fourteen patients with glioblastoma and 12 healthy controls were included. In contrast to MTR_asym, the LDA is modeling the direct water saturation and the semi‐solid magnetization transfer, allowing a separate evaluation of the aliphatic nuclear Overhauser effect and the APT‐CEST. The results of our study show that the pH values obtained by ³¹P MRSI correspond well with both methods describing the APT‐CEST contrast. Two‐sample t‐test showed significant differences in MTR_asym, LDA and pH obtained by ³¹P MRSI for regions of interest in glioblastoma, contralateral control areas and normal appearing white matter (P < 0.001). A slightly improved correlation between the amide signal and pH was found after performing LDA (r = 0.78) compared with MTR_asym (r = 0.70). While both methods can be used to monitor pH changes, the LDA approach appears to be better suited.