Iron oxide nanoparticles as positive T1 contrast agents for low-field magnetic resonance imaging at 64 mT

We have investigated the efficacy of superparamagnetic iron oxide nanoparticles (SPIONs) as positive T₁ contrast agents for low-field magnetic resonance imaging (MRI) at 64 millitesla (mT). Iron oxide-based agents, such as the FDA-approved ferumoxytol, were measured using a variety of techniques to evaluate T₁ contrast at 64 mT. Additionally, we characterized monodispersed carboxylic acid-coated SPIONs with a range of diameters (4.9-15.7 nm) in order to understand size-dependent properties of T₁ contrast at low-field. MRI contrast properties were measured using 64 mT MRI, magnetometry, and nuclear magnetic resonance dispersion (NMRD). We also measured MRI contrast at 3 T to provide comparison to a standard clinical field strength. SPIONs have the capacity to perform well as T₁ contrast agents at 64 mT, with measured longitudinal relaxivity (r₁) values of up to 67 L mmol⁻¹ s⁻¹, more than an order of magnitude higher than corresponding r₁ values at 3 T. The particles exhibit size-dependent longitudinal relaxivities and outperform a commercial Gd-based agent (gadobenate dimeglumine) by more than eight-fold at physiological temperatures. Additionally, we characterize the ratio of transverse to longitudinal relaxivity, r₂/r₁ and find that it is ~ 1 for the SPION based agents at 64 mT, indicating a favorable balance of relaxivities for T₁-weighted contrast imaging. We also correlate the magnetic and structural properties of the particles with models of nanoparticle relaxivity to understand generation of T₁ contrast. These experiments show that SPIONs, at low fields being targeted for point-of-care low-field MRI systems, have a unique combination of magnetic and structural properties that produce large T₁ relaxivities.