Magnetic resonance chemical exchange saturation transfer imaging and nanotechnology

Abstract

Chemical exchange saturation transfer (CEST) agents and paramagnetic CEST (PARACEST) agents display bound water signals that exchange protons with the bulk water. CEST magnetic resonance imaging (MRI) relies on exchangeable protons that resonate at a chemical shift that is distinguishable from the bulk water signal. In some cases, paramagnetic chelates are utilized to shift the bound water frequency further away from the bulk water. Radiofrequency prepulses applied at the appropriate frequency can saturate the exchangeable protons, which transfer into the bulk water pool and lead to reduced equilibrium magnetization. Therefore, CEST and PARACEST agents allow the image contrast to be switched 'on' and 'off' by simply changing the pulse sequence parameters. One of the main limitations with this approach is the inherent insensitivity of MRI to CEST and PARACEST agents. Nanoscale carriers have been developed to improve the limit of detection for these agents, demonstrating the feasibility of in vivo molecular or cellular MRI based on CEST or PARACEST contrast. These carriers have been based on a number of different nanoparticle constructs, such as liposomes, dendrimers, polymers, adenovirus particles, and perfluorocarbon nanoparticles. The unique MRI properties of CEST and PARACEST nanoparticle systems have spawned research into an array of potential medical applications.