Abstract
PurposeIn 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.MethodsDifferent 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.ResultsBy 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.Conclusiondual-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.
Highlights
Solid tumors have been reported to have a slightly acidic extracellular pH range of 6.4–6.9, while the pH of normal tissues is neutral and ranges from 7.2–7.5 [1, 2]
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.The lesion size was similar between chemical exchange saturation transfer (CEST) pH magnetic resonance imaging (MRI) and T2-weighted imaging
To elucidate differences in ioversol signal intensities in common benign and malignant liver tumors, we evaluated the differences between the tumor region and tumor-adjacent normal liver tissue of 15 patients diagnosed with hepatic carcinoma and 5 patients diagnosed with hepatic hemangioma using a paired Student’s t-test
Summary
Solid tumors have been reported to have a slightly acidic extracellular pH (pHe) range of 6.4–6.9, while the pH of normal tissues is neutral and ranges from 7.2–7.5 [1, 2]. Metabolic dysregulation significantly contributes to glycolytic processes, causing excess intracellular lactic acid accumulation in tumors. Previous studies on alkalinizing treatments have reported that bicarbonate therapy significantly reduces metastasis in mouse models of breast and prostate cancer, primarily by decreasing the release of active cathepsin B into the pericellular space [13, 14]. Alkalinizing treatments, which are required for tumor pHe normalization, potentially cause metabolic alkalosis at high doses. Accurate measurement of the pHe of tumors and normal tissue can help regulate alkalinizing treatment
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