Magnetization Transfer Contrast and Chemical Exchange Saturation Transfer MRI. Features and analysis of the field-dependent saturation spectrum

Abstract

ABSTRACT Magnetization Transfer Contrast (MTC) and Chemical Exchange Saturation Transfer (CEST) experiments measure the transfer of magnetization from molecular protons to the solvent water protons, an effect that becomes apparent as an MRI signal loss (“saturation”). This allows molecular information to be accessed with the enhanced sensitivity of MRI. In analogy to Magnetic Resonance Spectroscopy (MRS), these saturation data are presented as a function of the chemical shift of participating proton groups, e.g. OH, NH, NH2, which is called a Z‐spectrum. In tissue, these Z‐spectra contain the convolution of multiple saturation transfer effects, including nuclear Overhauser enhancements (NOEs) and chemical exchange contributions from protons in semi‐solid and mobile macromolecules or tissue metabolites. As a consequence, their appearance depends on the magnetic field strength (B0) and pulse sequence parameters such as B1 strength, pulse shape and length, and interpulse delay, which presents a major problem for quantification and reproducibility of MTC and CEST effects. The use of higher B0 can bring several advantages. In addition to higher detection sensitivity (signal‐to‐noise ratio, SNR), both MTC and CEST studies benefit from longer water T1 allowing the saturation transferred to water to be retained longer. While MTC studies are non‐specific at any field strength, CEST specificity is expected to increase at higher field because of a larger chemical shift dispersion of the resonances of interest (similar to MRS). In addition, shifting to a slower exchange regime at higher B0 facilitates improved detection of the guanidinium protons of creatine and the inherently broad resonances of the amine protons in glutamate and the hydroxyl protons in myoinositol, glycogen, and glucosaminoglycans. Finally, due to the higher mobility of the contributing protons in CEST versus MTC, many new pulse sequences can be designed to more specifically edit for CEST signals and to remove MTC contributions. HIGHLIGHTSBasics of nuclear Overhauser enhancement (NOE) and chemical exchange saturation transfer (CEST).Comprehensive description of the features of the endogenous saturation spectrum (Z‐spectrum) in MRI.Explanation of advantages of using higher magnetic field for CEST MRI.Critical assessment of CEST data analysis approaches.Critical assessment of early CEST applications for the brain.