Construction of a quantitative extracellular pH map of rat brain glioma using CEST-MRI with iobitridol as the...

This study aimed to evaluate whether chemical exchange saturation transfer (CEST) imaging, in combination with the nonionic X-ray iodinated contrast agent Iobitridol, can detect extracellular pH (pHe) in rats with gliomas and enable the construction of quantitative pHe maps. CEST pH imaging was performed both on Iobitridol phantoms and on rat models bearing brain gliomas, using a 7.0 Tesla small animal MRI scanner (Agilent Technologies) and employing varying radiofrequency (RF) powers (1.5, 3.0, and 6.0 µT) based on the ratio of apparent exchange-dependent relaxation (AREX_ratio) technique (specifically, 1.5/6.0 µT and 3.0/6.0 µT). The results indicated that AREX_ratio can more effectively eliminate the influence of magnetization transfer (MT) effects from the CEST signal, thereby enabling more accurate quantification of pH. In vivo CEST pHe imaging distinctly delineated the glioma regions, and quantitative analysis demonstrated that the mean extracellular pH values within gliomas were closely aligned and exhibited an acidic profile. These results further verify the reliability and accuracy of CEST imaging for quantitative assessment of the tumor microenvironment's acidity in gliomas. In conclusion, this study is the first to demonstrate that non-invasive CEST imaging can accurately detect the acidic extracellular microenvironment of brain gliomas and produce quantitative pHe maps with good spatial resolution, highlighting its significant potential for clinical translation.