A General MRI-CEST Ratiometric Approach for pH Imaging: Demonstration ofin VivopH Mapping with Iobitridol

Abstract

Chemical exchange saturation transfer (CEST) is a novel contrast mechanism for magnetic resonance imaging (MRI). CEST MRI selectively saturates exchangeable protons that are transferred to MRI-detectable bulk water signal. MRI-CEST (pH)-responsive agents are probes able to map pH in the microenvironment in which they distribute. To minimize the confounding effects of contrast agent concentration, researchers have developed ratiometric CEST imaging, which investigates contrast agents containing multiple magnetically non-equivalent proton groups, whose prototropic exchange have different pH responses. However, conventional ratiometric CEST MRI imposes stringent requirements on the selection of CEST contrasts agents. In this study, a novel ratiometric pH MRI method based on the analysis of CEST effects under different radio frequency irradiation power levels was developed. The proposed method has been demonstrated using iobitridol, an X-ray contrast agent analog of iopamidol but containing a single set of amide protons, both in vitro and in vivo.

Relaxation‐compensated CEST‐MRI at 7 T for mapping of creatine content and pH – preliminary application in human muscle tissue in vivo

“…It is interesting to note that T 1 -correction is not necessary for this ratio. Similar ratiometric approaches have been reported before (19,20).…”

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

“…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. 19,51 Finally, iodine concentration as high as 3 to 4 mg I/mL has been measured in human gliomas, 52 and novel delivery approaches may further enhance CA accumulation within the tumor, 53 facilitating iodinated CAs-enhanced CEST imaging at clinical magnetic fields.…”

“…[14][15][16][17][18] Recently, a radio frequency (RF) power-based ratiometric approach has been proposed for agents containing a single exchangeable proton pool for measuring in vivo tumor extracellular pH with the same accuracy as with iopamidol. 19 It is important to note that pH imaging with iodinated agents has been successfully demonstrated in a human volunteer with a 3 T MR scanner. 20 Iodinated agents display a relatively large chemical shift between amide and bulk water protons, which confers favorable CEST imaging properties in comparison to molecules such as glucose and glucose analogs.…”

Overcoming the concentration-dependence of responsive probes for magnetic resonance imaging

“…Using the radiofrequency power mismatch approach, Aime and co-workers demonstrated both in vitro and in vivo pH detection using radiofrequency powers of 1.5, 3, and 6 µT. 77 $$\text{italicradio frequency power mismatch}=\frac{{[(1-\mathrm{S}\mathrm{T})/\mathrm{S}\mathrm{T}]}_{RF1}}{{[(1-\mathrm{S}\mathrm{T})/\mathrm{S}\mathrm{T}]}_{RF2}}$$ …”