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

Yanyan Tang; Gang Xiao; Zhiwei Shen; Caiyu Zhuang; Yudan Xie; Xiaolei Zhang; Zhongxian Yang; Jitian Guan; Yuanyu Shen; Yanzi Chen; Lihua Lai; Yuanfeng Chen; Shuo Chen; Zhuozhi Dai; Runrun Wang; Renhua Wu

doi:10.3389/fonc.2020.578985

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

Front Oncol. 2020 Nov 2:10:578985. doi: 10.3389/fonc.2020.578985. eCollection 2020.

Authors

Yanyan Tang^{1

2}, Gang Xiao³, Zhiwei Shen⁴, Caiyu Zhuang¹, Yudan Xie⁵, Xiaolei Zhang⁶, Zhongxian Yang¹, Jitian Guan¹, Yuanyu Shen¹, Yanzi Chen¹, Lihua Lai¹, Yuanfeng Chen¹, Shuo Chen¹, Zhuozhi Dai¹, Runrun Wang¹, Renhua Wu^{1

7}

Affiliations

¹ Department of Medical Imaging, The Second Affiliated Hospital, Shantou University Medical College, Shantou, China.
² Department of Medical Imaging, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
³ Department of Mathematics and Statistics, Hanshan Normal University, Chaozhou, China.
⁴ Philips Healthcare, Beijing, China.
⁵ Department of General Surgery, The Second Affiliated Hospital, Shantou University Medical College, Shantou, China.
⁶ College of Air Traffic Management, Civil Aviation Flight University of China, Guanghan, China.
⁷ Provincial Key Laboratory of Medical Molecular Imaging, Shantou, China.

Abstract

Purpose: 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.

Keywords: chemical exchange saturation transfer magnetic resonance imaging (MRI); extracellular pH; hepatic carcinoma; hepatic hemangioma; ioversol.