Iron Oxide Nanoparticles as Positive T1 Contrast Agents for Low-Field Magnetic Resonance Imaging at 64 mT

Abstract We have investigated the efficacy of superparamagnetic iron oxide nanoparticles (SPIONs) as positive T 1 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 T 1 contrast at 64 mT. Additionally, we characterized monodispersed carboxylic acid-coated SPIONs with a range of diameters (4.9 nm to 15.7 nm) in order to understand size-dependent properties of T 1 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 T 1 contrast agents at 64 mT, with measured longitudinal relaxivity (r 1 ) values of up to 67 L mmol − 1 s − 1 , more than an order of magnitude higher than corresponding r 1 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, r 2 /r 1 and find that it is ~ 1 for the SPION based agents at 64 mT, indicating a favorable balance of relaxivities for T 1 -weighted contrast imaging. We also correlate the magnetic and structural properties of the particles with models of nanoparticle relaxivity to understand generation of T 1 contrast. These experiments show that SPIONs, at low fields being targeted for point-of-care low-field MRI systems, have a unique combination of a large moment plus water-diffusion correlation times close to the proton precession period, that provide very large T 1 relaxivities.