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 (31 P 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 [MTRasym ] and Lorentzian difference analysis [LDA]) for analyzing the Z-spectrum have been correlated with pH values obtained by 31 P MRSI. Fourteen patients with glioblastoma and 12 healthy controls were included. In contrast to MTRasym , 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 31 P MRSI correspond well with both methods describing the APT-CEST contrast. Two-sample t-test showed significant differences in MTRasym , LDA and pH obtained by 31 P 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 MTRasym (r = 0.70). While both methods can be used to monitor pH changes, the LDA approach appears to be better suited.