Monte Carlo simulations of NMR high-field <i>T</i> 2 relaxation induced by superparamagnetic iron oxide nanoparticles coated with a layer with slowed water diffusion

In nuclear magnetic resonance imaging, superparamagnetic iron oxide nanoparticles (SPIONs) are an alternative contrast agent to gadolinium, as they can be used as negative contrast agents. They are usually coated with polymers or sugars for stability and biocompatibility. Coatings are at best semipermeable to water. In existing theories of SPION-induced nuclear magnetic resonance contrast, T2 contrast relies on diffusion of water protons in the magnetic field inhomogeneities created by the nanoparticles; therefore, reduced diffusion in the coating is expected to impact the relaxation rate of protons surrounding SPIONs. In this study, the impact on transverse relaxation of a coating layer surrounding SPIONs in which water diffusion is slowed is studied through a Monte Carlo algorithm. It is shown that for small SPIONs, the presence of a coating does affect the transverse relaxation rate R2. The transverse relaxation rate is higher and, therefore, SPION-induced contrast performance is enhanced for nanoparticles with a magnetic iron oxide core smaller than 10 nm in radius, with sufficiently thick coatings with water diffusion coefficients typical of polyethylene glycol, dextran, and gelatin. Those R2 variations can be semi-quantitatively understood using an exchange model, where the protons inside the coating contribute to the relaxation rate with a weight that takes into account their residence time in the coating. Eventually, this study provides guidelines for SPION synthesis for optimum contrast performance: small SPIONs with bigger coatings where the diffusion coefficient of water is 3-10 times lower than the self-diffusion coefficient of water perform the best as T2 contrast agents. Such coatings can be polyethylene glycol or polyacrylic acid, dextran, and gelatin.