Ratiometric chemical exchange saturation transfer pH mapping using two iodinated agents with nonequivalent amide protons and a single low saturation power

Quan Tao; Peiwei Yi; Zimeng Cai; Zelong Chen; Zongwu Deng; Ruiyuan Liu; Yanqiu Feng

doi:10.21037/qims-21-1229

Ratiometric chemical exchange saturation transfer pH mapping using two iodinated agents with nonequivalent amide protons and a single low saturation power

Quant Imaging Med Surg. 2022 Jul;12(7):3889-3902. doi: 10.21037/qims-21-1229.

Authors

Quan Tao^#^{1

2

3

4}, Peiwei Yi^#^{1

2

3

4}, Zimeng Cai^{1

2

3

4}, Zelong Chen⁵, Zongwu Deng⁶, Ruiyuan Liu^{1

2

3

4}, Yanqiu Feng^{1

2

3

4}

Affiliations

¹ School of Biomedical Engineering, Southern Medical University, Guangzhou, China.
² Guangdong Provincial Key Laboratory of Medical Image Processing, Southern Medical University, Guangzhou, China.
³ Guangdong Province Engineering Laboratory for Medical Imaging and Diagnostic Technology, Southern Medical University, Guangzhou, China.
⁴ Key Laboratory of Mental Health of the Ministry of Education & Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Southern Medical University, Guangzhou, China.
⁵ Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
⁶ CAS Key Laboratory of Nano-Bio Interface and Division of Nanobionics, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, China.

^# Contributed equally.

Abstract

Background: As an essential physiological parameter, pH plays a critical role in maintaining cellular and tissue homeostasis. The ratiometric chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) method using clinically approved iodinated agents has emerged as one of the most promising noninvasive techniques for pH assessment.

Methods: In this study, we investigated the ability to use the combination of two different nonequivalent amide protons, chosen from five iodinated agents, namely iodixanol, iohexol, iobitridol, iopamidol, and iopromide, for pH measurement. The ratio of two nonequivalent amide CEST signals was calculated and compared for pH measurements in the range of 5.6 to 7.6. To quantify the CEST signals at 4.3 and 5.5 parts per million (ppm), we employed two analytic methods: magnetization transfer ratio asymmetry and Lorentzian fitting analysis. Lastly, the established protocol was used to measure the pH values in healthy rat kidneys (n=5).

Results: The combination of iodixanol and iobitridol at a ratio of 1:1 was found to be suitable for pH mapping. The saturation power level (B₁) was also investigated, and a low B₁ of 1.5 µT was adopted for subsequent pH measurements. Improved precision and an extended pH detection range were achieved using iodixanol and iobitridol (1:1 ratio) and a single low B₁ of 1.5 µT in vitro. In vivo renal pH values were measured as 7.23±0.09, 6.55±0.15, and 6.29±0.23 for the cortex, medulla, and calyx, respectively.

Conclusions: These results show that the ratiometric CEST method using two iodinated agents with nonequivalent amide protons could be used for in vivo pH mapping of the kidney under a single low B₁ saturation power.

Keywords: Magnetic resonance imaging (MRI); chemical exchange saturation transfer (CEST); iodinated agents; kidney; pH mapping; ratiometric.