Noninvasive Detection of Extracellular pH in Human Benign and Malignant Liver Tumors Using CEST MRI

Abstract

In this study, we aimed to use 3T magnetic resonance imaging (MRI), which is clinically available, to determine the extracellular pH (pHe) of liver tumors and prospectively evaluate the ability of chemical exchange saturation transfer (CEST) MRI to distinguish between benign and malignant liver tumors. Methods: Different radiofrequency irradiation schemes were assessed for ioversol-based pH measurements at 3T. CEST effects were quantified in vitro using the asymmetric magnetization transfer ratio (MTRasym) at 4.3 ppm from the corrected Z spectrum. Generalized ratiometric analysis was conducted by rationing resolved ioversol CEST effects at 4.3 ppm at a flip angle of 60 and 350°. Fifteen patients recently diagnosed with hepatic carcinoma and five patients diagnosed with hepatic hemangioma [1 male; mean age, 48.6 (range, 37-59) years] were assessed. Results: By conducting dual-power CEST MRI, the pH of solutions was determined to be 6.0-7.2 at 3T in vitro. In vivo, ioversol signal intensities in the tumor region showed that the extracellular pH in hepatic carcinoma was acidic(mean ± standard deviation, 6.66 ± 0.19), whereas the extracellular pH was more physiologically neutral in hemangioma (mean ± standard deviation, 7.34 ± 0.09).The lesion size was similar between CEST pH MRI and T2-weighted imaging. Conclusion: dual-power CEST MRI can detect extracellular pH in human liver tumors and can provide molecular-level diagnostic tools for differentiating benign and malignant liver tumors at 3T.

Impact of Inhibition of the Mitochondrial Pyruvate Carrier on the Tumor Extracellular pH as Measured by CEST-MRI

“…Our study adds to the previous demonstration on the utility of longitudinal monitoring of tumor acidosis during anti-cancer treatments [ 30 , 31 , 32 ]. As the feasibility of using CEST-MRI has already been demonstrated in patients for pH measurement [ 28 , 29 , 57 , 58 ], it is likely that this technology could be useful as imaging biomarker for guidance of treatments targeting tumor metabolism.…”

Perivascular Spaces, Glymphatic System and MR

“…Information on compounds is thus obtained indirectly by detecting the free water signal changes. This emerging MRI technology can be used to detect body temperature, pH, enzyme activity and metabolites (glucose, glutamate, creatine and inositol) ( 101 ). In a porcine model of impaired glymphatic function, intrinsic compounds in the blood, lymph, and CSF were distinguished using CEST MRI at 7 Tesla, and the CEST effect of lymph is extremely significant compared to that of blood and CSF, which the author refers to as the “Lym-CEST” effect ( 102 ).…”

A Brief History and Future Prospects of CEST MRI in Clinical Non-Brain Tumor Imaging

“…Tumor detection : Tang et al [ 72 ] performed ioversol-based pH mapping on a 3 T scanner. The CEST-related signal was separated using MTR asym at 4.3 ppm and the pH effect was measured by a specially designed ratiometric value that was calculated from the signals that were obtained at two flip angles ( Figure 6 ).…”

“…( d ) The pHe map for hepatic hemangioma; the CEST pHe was consistent with the surrounding liver tissue, confirming the hemangioma to be benign. Reproduced with permission from Frontiers 2020 (DOI: 10.3389/fonc.2020.578985) [ 72 ].…”