User:Mmfas13/Magnetic particle imaging

Superparamagnetic Tracer

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The tracers used in magnetic particle imaging (MPI) are superparamagnetic iron oxide nanoparticles (SPIONs). They are composed of a magnetite (Fe₃O₄) or maghemite (Fe₂O₃) core surrounded by a surface coating (commonly dextran, carboxydextran, or polyethylene glycol).

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The SPIO tracer used in magnetic particle imaging is detectable within biological fluids, such as the blood. This fluid is very responsive to even weak magnetic fields, and all of the magnetic moments will line up in the direction of an induced magnetic field. These particles can be used because the human body does not contain anything which will create magnetic interference in imaging. As the sole tracer, the properties of SPIONs are of key importance to the signal intensity and resolution of MPI. Iron oxide nanoparticles, due to their magnetic dipoles, exhibit a spontaneous magnetization that can be controlled by an applied magnetic field. Therefore, the performance of SPIONs in MPI is critically dependent on their magnetic properties, such as saturation magnetization, magnetic diameter, and relaxation mechanism.

The figure to the right is a representative image of a Point Spread Function (PSF) obtained using Relax Mode in MPI scanner, pointing out the signal intensity and full width at half maximum (FWHM) which corresponds to the signal resolution.

Upon application of an external magnetic field, the relaxation of SPIONs can be governed by two mechanisms, Néel, and Brownian relaxation. When the entire particle rotates with respect to the environment, it is following Brownian relaxation, which is affected by the physical diameter. When only the magnetic dipole rotates within the particles, the mechanism is called Néel relaxation, which is affected by the magnetic diameter. According to the Langevin model of superparamagnetism, the spatial resolution of MPI should improve cubically with the magnetics diameter, which can be obtained by fitting magnetization versus magnetic field curve to a Langevin model. However, more recent calculations suggest that there exists an optimal SPIONs magnetic size range (~26 nm) for MPI. This is because of blurring caused by Brownian relaxation of large magnetics size SPIONs. Although magnetic size critically affects the MPI performance, it is often poorly analyzed in publications reporting applications of MPI using SPIONs. Often, commercially available tracers or home-made tracers are used without thorough magnetic characterization. Importantly, due to spin canting and disorder at the surface, or due to the formation of mixed-phase nanoparticles, the equivalent magnetic diameter can be smaller than the physical diameter. And magnetic diameter is critical because of the response of particles to an applied magnetic field dependent on the magnetic diameter, not physical diameter. The largest equivalent magnetic diameter can be the same as the physical diameter. A recent review paper by Chandrasekharan et al. summarizes properties of various iron oxide contrast agents and their MPI performance measured using their in-house Magnetic Particle Spectrometer, shown in the picture here. It should be pointed out that the core diameter listed in the table is not necessarily the magnetic diameter. The table provides a comparison of all current published SPIONs for MPI contrast agents. As seen in the table, LS017, with a SPION core size of 28.7 nm and synthesized through heating up thermal decomposition with post-synthesis oxidation, has the best resolution compared with others with lower core size. Resovist (Ferucarbotran), consisting of iron oxide made via coprecipitation, is the most commonly used and commercially available tracer. However, as suggested by Gleich et al., only 3% of the total iron mass from Resovist contributes to the MPI signal due to its polydispersity, leading to relatively low MPI sensitivity. The signal intensity of MPI is influenced by both the magnetic core diameter and the size distribution of SPIONs. Comparing the MPI sensitivity listed in the above table, LS017 has the highest signal intensity (54.57 V/g of Fe) as particles are monodisperse and possess a large magnetic diameter compared with others.

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The surface coating of SPIONs is of key importance as well, since it influences the stability, pharmacokinetics behavior, and biodistribution of particles in biological environments. The biodistribution of carboxy-dextran and PEG-modified SPIONs were studied by Keselman et al. using MPI. Results suggested that PEG-modified SPIONs had a relatively long blood half-life of 4.2 h before uptake by the liver and spleen, compared with carboxy-dextran coated SPIONs which cleared rapidly to the liver. The choice of surface coating influences the potential applications using MPI. A carboxy-dextran coated SPION is useful for imaging of liver while PEG-modified particles are more preferred for long-term circulation.

Taking all these concepts and information into consideration, we can begin to define that the “ideal” particles in the context of producing better MPI sensitivity and resolution should possess the following characteristics:

• magnetic core size around 26 nm and close to the physical diameter
• monodisperse
• suitable surface coating

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The surface coating plays a key role in determining the behavior of the SPIONs. It minimizes unwanted interactions between the iron oxide cores (for example, counteracting attractive forces between the particles to prevent aggregation), increases SPION compatibility with the biological environment, and can also be used to tailor SPION performance to particular imaging applications. Different coatings cause changes in cellular uptake, blood circulation, and interactions with the immune system, influencing where the SPIONs end up in the body and after how long. For example, SPIONs coated with carboxydextran have been shown to clear to the liver almost immediately after injection, while those with a polyethylene glycol (PEG) coating remain in circulation for hours before being cleared from the blood. These behaviors would make the carboxydextran-coated SPION better optimized for liver imaging and the PEG-coated SPION more suitable for vascular imaging.