PARACEST contrast agents

The previous chapter introduced the concept of using chemical exchange saturation transfer (CEST) methods to produce contrast in magnetic resonance (MR) images. Since MR image intensity is largely determined by the water content of tissues and the relaxation characteristics of that water, any molecule that is in chemical exchange with water can potentially be used to transfer saturated spins into the pool of water protons, and hence used to initiate CEST contrast. In biology, this includes any molecule, large or small, that contains an exchangeable proton such as –NH, –OH, –SH, –PO₄H, or, in unusual circumstances, –CO₂H. The protons in such groups typically have nuclear magnetic resonance (NMR) chemical shifts that differ from tissue water by <5 ppm. This makes it difficult, if not impossible, to saturate one of these exchangeable spins without partial saturation of at least some of the bulk water spins as well. More will be presented on this later. One could expand the choices of exchangeable spins from simple proton systems (–NH, –OH, etc.) to a water molecule (H₂O) if the chemical shift degeneracy between water molecules in different chemical environments or compartments could be lifted. As we shall see, this is the role fulfilled by paramagnetic metal ions and, in particular, the trivalent lanthanide (III) ions.