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

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 (B 1 ) was also investigated, and a low B 1 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 B 1 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 B 1 saturation power.

Diagnostic and prognostic performance of renal compartment volume and the apparent diffusion coefficient obtained from magnetic resonance imaging in mild, moderate and severe diabetic kidney disease

“…Magnetic resonance imaging (MRI) offers noninvasive assessment of renal macromorphology (e.g., renal volume and cysts) and microstructure (e.g., fibrosis and edema) in health and disease ( 10 - 13 ). Total kidney volume has been demonstrated to be a viable diagnostic metric and a macromorphology marker for renal disease progression ( 14 - 16 ).…”

Development of cationic peptide-based hydrogels loaded with iopamidol for CEST-MRI detection

“…1) has been the first iodinated CT agent considered for CEST-MRI, 4 and it has also been demonstrated to act as an excellent in vivo pH reporter. 5–7…”

“…1) has been the first iodinated CT agent considered for CEST-MRI, 4 and it has also been demonstrated to act as an excellent in vivo pH reporter. [5][6][7] CEST agents have been investigated for many clinically relevant applications, including the possibility of labeling hydrogels (HGs), thus making them detectable by MRI. Hydrogels are supramolecular network structures able to retain a high amount of water and mainly studied as platforms to encapsulate and release bioactive compounds 8,9 or as scaffolds for supporting living cells.…”

Editorial for “A Pilot Study of Ratiometric Creatine CEST MRI Assessment of Rabbit Skeletal Muscle Energy Metabolism at 3 T”

“…Ratiometric CEST can be implemented through various methods, offering flexibility in experimental design. For example, ratiometric CEST can be performed by saturation of two exchanging groups at the same saturation power 7 or by varying the saturation time and/or saturation power levels on the same group, such as multi‐angle ratiometric approach, 8 the RF amplitude‐based CrCEST ratiometric pH imaging, 9 and so on.…”