Quantification of iopamidol multi-site chemical exchange properties for ratiometric chemical exchange saturation transfer (CEST) imaging of pH

Abstract

pH-sensitive chemical exchange saturation transfer (CEST) MRI holds great promise for in vivo applications. However, CEST effect depends on not only exchange rate and hence pH, but also on the contrast agent concentration, which must be determined independently for pH quantification. Ratiometric CEST MRI normalizes the concentration effect by comparing CEST measurements of multiple labile protons to simplify pH determination. Iopamidol, a commonly used X-Ray contrast agent, has been explored as a ratiometric CEST agent for imaging pH. However, iopamidol CEST properties have not been solved, determination of which is important for optimization and quantification of iopamidol pH imaging. Our study numerically solved iopamidol multi-site pH-dependent chemical exchange properties. We found that iopamidol CEST MRI is suitable for measuring pH between 6 and 7.5 despite that T1 and T2 measurements varied substantially with pH and concentration. The pH MRI precision decreased with pH and concentration. The standard deviation of pH determined from MRI was 0.2 and 0.4 pH unit for 40 and 20 mM iopamidol solution of pH 6, and it improved to be less than 0.1 unit for pH above 7. Moreover, we determined base-catalyzed chemical exchange for 2-hydrooxypropanamido (ksw=1.2*10pH−4.1) and amide (ksw=1.2*10pH−4.6) protons that are statistically different from each other (P<0.01, ANCOVA), understanding of which should help guide in vivo translation of iopamidol pH imaging.

Multislice CEST MRI improves the spatial assessment of tumor pH

“…However, the k 0 value for the amide proton resonating at 5.6 ppm was determined with lower precision. These fitted parameters for iopamidol were different than previously reported results because our study was performed at 37°C, whereas the previous study was performed at 25°C. The values of k b and k 0 for the hydroxyl protons resonating at 0.73 ppm could not be determined with any precision due to the proximity of this CEST signal near the direct saturation of water.…”

In Vitro and In Vivo Assessment of Nonionic Iodinated Radiographic Molecules as Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Tumor Perfusion Agents

“…In addition, T 1 decreases with field strength, reducing sensitivity at 3 T. Fortunately, there are extensive optimization options that we can choose to maximize the detection sensitivity, that will be investigated in future works. 44,45 In addition, novel postprocessing algorithms that reduce the concomitant endogenous semisolid magnetization transfer effect may further enhance detection sensitivity at lower fields. 27,46-50 Furthermore, the demonstration of a novel RF power-based ratiometric approach for pH mapping even for molecule possessing only a single proton pool can also be exploited for these agents.…”

Ratiometric NOE(−1.6) contrast in brain tumors

“…Previously, several variations of CEST, such as amide proton transfer (APT), glutamate CEST, creatine CEST, CEST imaging of glucose and its derivatives, paramagnetic agent CEST, and acidoCEST, have been developed to detect endogenous and exogenous agents. To further quantify the exchange rate, which is relevant to the intracellular or extracellular pH, a ratiometric approach, using the ratio of two CEST signals that have different dependences on the exchange rate but the same dependences on other non‐specific factors (e.g., solute pool concentration), was also developed . This ratiometric approach can remove the non‐specific factors and provide a specific exchange rate‐weighted signal.…”