ABSTRACT

Magnetic resonance imaging (MRI) is a versatile technology that

employs water content and water relaxation properties to image

the anatomy and physiology of the body. Currently, MRI has

been widely used in hospitals for the localization, diagnosis, and

characterization of cancer [1, 2], stroke [3], and other diseases,

and for the assessment of treatment effects. In addition to the

conventional MRI sequences, such as T1-weighted (T1w) and T2weighted (T2w), several advanced, functional MRI techniques [4, 5], such as perfusion imaging, diffusion imaging, and proton MR

spectroscopic imaging, have been emerging in clinical research

protocols. As MRI is applied further at the molecular level, more

possibilities for disease diagnosis and treatment assessment will

become evident [6, 7]. Currently, most molecular and cellular

MRI studies rely on the administration of paramagnetic or super-

paramagnetic metal-based substrates that are potentially harmful.

Ideally, molecular imagingwould exploit endogenousmolecules that

can be probed non-invasively using existing hardware. Pioneered by

Balaban et al. [8-10], chemical exchange saturation transfer (CEST)

imaging is a new molecular MRI method that allows detection

of low-concentration, endogenous or exogenous chemicals with

exchangeable protons through the water signal [11-13]. In the

past several years, many new CEST contrast agents have been

designed-diamagnetic [14], paramagnetic (paraCEST) [15, 16], and

even hyperpolarized (hyperCEST) [17]—and the validation of new

types of applications is progressing rapidly on many fronts.