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Posted on Thu, Aug 09, 2018

Superparamagnetic iron-oxide nanoparticles (SPION)-enhanced MRI imaging

Superparamagnetism is a type of magnetism that lies between that of a permanent magnet and a paramagnet. Recall that a permanent magnet is always magnetic at temperatures below its Curie Temperature even in zero applied magnetic field, whereas a paramagnet is not magnetic at zero applied field but can become magnetic when an external magnetic field is applied. The potential for a paramagnet to be induced to have magnetization is called magnetic susceptibility. A superparamagnet behaves similarly to a paramagnet. The “super” means that it has a higher magnetic susceptibility than a regular paramagnet when a magnetic field is applied. Superparamagnets are typically made of iron oxide or other ferrous materials, and they are extremely small, on the order of 10-100 nanometers.

superparamagnetism 

The high magnetic susceptibility of SPIONs makes them ideal for use in biotechnology in contexts such as biomagnetic separation, magnetic drug targeting, hyperthermia, and imaging. These particles are used in conjunction with magnetic resonance imaging (MRI) to identify infection and inflammation. The particles are taking the place of more traditional contrast chemicals as they are proving to offer higher resolution and better quality images. In SPION-enhanced MRI, the paramagnetic behavior of the particles is exploited, and the induced magnetic moments of the particles create local magnetic fields that affect the nearby water molecules. The machine detects the T1, T2 relaxation times of those water molecules. These times differ according to tissue type. Mapping the relaxation times produces a high-resolution image of internal tissue. The T1 relaxation time is the rate at which excited spinning protons return to equilibrium and realign with the external magnetic field. The T2 relaxation time is the rate at which excited protons lose coherence with each other.  A T1-weighted scan shows all fat deposits as high intensity pixels in the image. A T2-weighted scan shows all fat and water as high intensity pixels. The two types of images are used together to map organs and diagnose disease.  After IV injection into humans and animals, larger SPIONs (> 16nm hydrodynamic diameter) are readily engulfed by macrophages. By tracking the T2 and T2* relaxation activity within macrophages, a site of inflammation or infection can be readily identified. 

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Larger SPIONs are better for T2 relaxation imaging, while smaller SPIONs are better for T1 relaxation imaging. Additionally, the creation of better SPIONs for T1 contrast involves increasing the ratio of maghemite (Fe2O3), which has a lower magnetization, to magnetite (Fe3O4). Another benefit of the smaller SPIONs (~5nm) is that they can be rapidly cleared from the body via the renal system. The larger SPIONs cannot be cleared by this method, and as a result stay in the body longer, which prevents longitudinal re-imaging.

SPION-enhanced MRI imaging can be used to identify other cells or tissues other than macrophages if an antigen-specific coating is applied to the particles. One example is the use of transfection agents, specific coatings, or functional moieties to allow the incorporation of SPIONs into transplanted stem cells. The stem cells can then be tracked as they move throughout the body. Another application is using MRI to identify cancer cells by coating the SPIONs with targets to bind to cancer cell specific antigens.

For more information:

Iron-Based Superparamagnetic Nanoparticle Contrast Agents for MRI of Infection and Inflammation. Alexander Neuwelt, Navneet Sidhu, Chien-An A. Hu, Gary Mlady, Steven C. Eberhardt, and Laurel O. Sillerud. American Journal of Roentgenology 2015 204:3, W302-W313.

In Vivo Molecular MRI Imaging of Prostate Cancer by Targeting PSMA with Polypeptide-Labeled Superparamagnetic Iron Oxide Nanoparticles. Zhu. Y. Int J Mol Sci. 2015 Apr 28;16(5):9573-87

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