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 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.

Review—Potential of Tunneling Magnetoresistance Coupled to Iron Oxide Nanoparticles as a Novel Transducer for Biosensors-on-Chip

“…• High Contrast: IONPs provide strong contrast in imaging techniques like MRI and MPI, allowing for the visualization of specific molecular interactions or targets. 44 • Biocompatibility: IONPs are generally considered biocompatible and can be used in biological and medical applications without significant toxicity concerns. 97 • Targeted Delivery: By functionalizing the nanoparticles with specific ligands, they can be used for targeted drug delivery, where they are directed to specific cells or tissues.…”

“…MRI Contrast Agents: IONPs exhibit strong magnetic properties, making them useful as contrast agents in magnetic resonance imaging (MRI) to enhance image quality. 44 2. Environmental Conservation: IONPs can be used to remove contaminants from water, such as heavy metals, organic pollutants, and dyes, through processes like adsorption and catalytic degradation.…”

“…Iron oxide nanoparticles (IONPs) are a type of MNPs that has gained significant attention due to their unique properties and potential applications. [42][43][44] These MNPs are composed of iron and oxygen atoms and can exist in different phases, such as magnetite (Fe 3 O 4 ) and maghemite (γ-Fe 2 O 3 ), 42 which exhibit magnetic behavior. They exhibit strong magnetic properties only when an external magnetic field is applied, and they lose some or all of their magnetization when the magnetic field is removed.…”

1H Spin–Lattice Relaxation Processes in Solutions of H2N–Fe3O4 Nanoparticles: Insights from NMR Relaxometry

“…This is in contrast to the extensive development of the theory of paramagnetic relaxation enhancement (PRE) describing the enhancement of 1 H relaxation in solutions of paramagnetic complexes. − The PRE theory ranges from simplified descriptions including (among other simplifications) single electron spin relaxation times even for high-spin paramagnetic complexes via several simplified concepts , to highly advanced models including a complex and frequency-dependent electron spin relaxation scenario − and going beyond the perturbation approach to relaxation processes. − The theory has been thoroughly tested, involving results from electron spin resonance to provide demanding criteria for the models . At the same time, the theoretical model of 1 H relaxation processes in solution of magnetic NPs has been proposed in a rather short series of papers. − As far as the experimental verification of the models is concerned, the studies are limited, despite very interesting experimental studies. , One should stress, at this stage, that to validate this theoretical approach, one requires relaxation data covering a broad range of magnetic fields (resonance frequencies). At high magnetic fields, the component of the electronic magnetic moment parallel to the external magnetic field reaches already its saturation (following the Brillouin function), and the electronic relaxation properties play a lesser role in the stochastic fluctuations of the magnetic dipole–dipole interactions between the magnetic moment of the nanoparticle and the nuclear magnetic moment, compared to translation diffusion of solvent molecules.…”

“…25−29 As far as the experimental verification of the models is concerned, the studies are limited, despite very interesting experimental studies. 30,31 One should stress, at this stage, that to validate this theoretical approach, one requires relaxation data covering a broad range of magnetic fields (resonance frequencies). At high magnetic fields, the component of the electronic magnetic moment parallel to the external magnetic field reaches already its saturation (following the Brillouin function), and the electronic relaxation properties play a lesser role in the stochastic fluctuations of the magnetic dipole−dipole interactions between the magnetic moment of the nanoparticle and the nuclear magnetic moment, compared to translation diffusion of solvent molecules.…”