Proton Chemical Exchange Saturation Transfer (CEST) MRS and MRI

Proton magnetic resonance spectroscopy (H-1 MRS) of biological systems has higher specificity than MRI because resonances of multiple metabolites can be distinguished, reflecting chemistry and physiology in situ. Unfortunately, this approach has very low sensitivity as the metabolites are typically at millimolar concentrations compared to the molar signal strength of water-based MRI. As a consequence, even though H-1 MRS is a powerful and common research tool, its inroad into daily clinical practice has been limited. Until very recently, H-1 MRS applications have focused on the resonances upfield (i.e., at lower frequency) of the water resonance. This article deals with protons that are generally not observed in a typical water-suppressed spectrum, namely, the exchangeable protons found predominantly downfield from water. These can usually be detected by MRS only if the transfer of water proton saturation (established during water suppression) is not a confounding factor, or by using water exchange (WEX) spectroscopy, in which RF labeling of the water protons is transferred to the exchangeable protons and subsequently detected. More importantly, it has recently become clear that the presence of such exchangeable protons on low concentration solute molecules can be detected via the water signal by RF labeling of these protons and subsequent transfer of this label to water protons. This process, leading to saturation of the water signal and enhancement of the effect through repeated exchange, can be used for the imaging of metabolite signals or exchangeable-proton-based contrast agents with enhanced sensitivity. This has given rise to the field of chemical exchange saturation transfer (CEST) MRI, which has greatly increased the potential for translating spectroscopic methods to the clinic. Examples include the measurement of pH, temperature, and enzyme activity as well as detection of cellular metabolites, ions, and proteins and peptides. In addition, bio-organic compounds can now be used for contrast agents, cell and nanoparticle labeling, and reporter genes.