Chemical exchange saturation transfer (CEST) and MR Z-spectroscopy in vivo: a review of theoretical approaches and methods.

Chemical exchange saturation transfer (CEST) of metabolite protons that undergo exchange processes with the abundant water pool enables a specific contrast for magnetic resonance imaging (MRI). The CEST image contrast depends on physical and physiological parameters that characterize the microenvironment such as temperature, pH, and metabolite concentration. However, CEST imaging in vivo is a complex technique because of interferences with direct water saturation (spillover effect), the involvement of other exchanging pools, in particular macromolecular systems (magnetization transfer, MT), and nuclear Overhauser effects (NOEs). Moreover, there is a strong dependence of the diverse effects on the employed parameters of radiofrequency irradiation for selective saturation which makes interpretation of acquired signals difficult. This review considers analytical solutions of the Bloch–McConnell (BM) equation system which enable deep insight and theoretical description of CEST and the equivalent off-resonant spinlock (SL) experiments. We derive and discuss proposed theoretical treatments in detail to understand the influence of saturation parameters on the acquired Z-spectrum and how the different effects interfere and can be isolated in MR Z-spectroscopy. Finally, we provide an overview of reported CEST effects in vivo and discuss proposed methods and technical approaches applicable to in vivo CEST studies on clinical MRI systems.