Going Above and Beyond: Achieving High Contrast and Higher Offset through Carbon Dot-Based diaCEST MRI Contrast Agent

Diamagnetic CEST (diaCEST) MRI contrast agents (CAs) have recently gained immense popularity by virtue of the fact that contrast can be switched on or off by merely changing a few experimental parameters, even after the agent is administered. However, the low efficiency and small solute-solvent offset of the contrast-generating exchangeable protons have so far prevented them from becoming a practical option for in vivo applications. Low efficiency demands high dosage, while small offset invites unwanted interference from the endogenous metabolites present in the human body. So far, the strategy for finding efficient diaCEST CAs involved searching for suitable molecules in which the exchangeable protons resonate as far as possible from water and have an optimum exchange rate. Very little effort has been devoted toward designing or converting to an efficient one from a less efficient existing CA. It was recently shown that hydrothermally synthesized carbon nanodots (CDs) have the ability to enhance contrast efficiency and to tune the pH response of certain diaCEST CAs. Here we show that a suitable combination of the synthesis technique and synthesis parameters can simultaneously enhance solute-solvent offset and contrast efficiency. In particular, we demonstrate 300% enhancement in offset and 100% enhancement in efficiency following the formation of carbon-dots from a urea-citric acid mixture.