MR-Based Methods for pH Measurement in Brain Tumors: Current Status and Clinical Potential

Abstract

Alteration in tissue pH is an indicator of many pathological processes.In tumors,the pH gradient exists between the intracellular(pHi) and extracellular(pHe) compartments.pHe is usually lower,and pHi could be higher or unchanging compared with normal tissue,which can be correlated with prognosis and response to treatment.In recent years,non-invasive MR-based methods have been developed to assess tissue pH in brain tumors.In addition to protons(1H) and phosphorus(31P),pH measurement approaches have been applied with other NMR nuclei such as fluorine(19F) and carbon(13C).By using hyperpolarized 13C-labelled bicarbonate,the average tumor interstitial pH was found significantly lower than the surrounding tissue in mouse tumor model.Gd(3+)-based pH sensors and chemical exchange-dependent saturation transfer(CEST) and paramagnetic(PARACEST) agents are useful for further delineation of brain tumors.This article primarily focuses on the measurement of pH in brain tumors with MR-based methods and relevant clinical potential.