Magnetic Resonance Molecular Imaging Using Iron Oxide Nanoparticles

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Zurkiya, Omar
Hu, Xiaoping
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Magnetic resonance imaging (MRI) is regularly used to obtain anatomical images, greatly advancing biomedical research and clinical health care today, but its full potential in providing functional, physiological, and molecular information is only beginning to emerge. The goal of magnetic resonance molecular imaging is to utilize MRI to acquire information on the molecular level. This dissertation is focused on ways to increase the use of MRI for molecular imaging using superparamagnetic iron oxide (SPIO) nanoparticle induced MRI contrast. This work is divided into three main sections: <B>1)<I> Elucidation of the contribution of size and coating properties to magnetic nanoparticle induced proton relaxation.</I></B> To maximize contrast generated without increasing particle size, new methods to increase effects on relaxivity must be developed. Experimental data obtained on a new class of biocompatible particles are presented, along with simulated data. The effects of coating size, proton exchange, and altered diffusion are examined. Simulations are presented confirming the effect of particle coatings on clustering-induced relaxivity changes, and an experimental system demonstrating the clustering effect is presented. <B>2)<I> Development of a diffusion-dependent, off-resonance imaging protocol for magnetic nanoparticles.</I></B> This work demonstrates an alternative approach, off-resonance saturation (ORS), for generating contrast sensitive to SPIO nanoparticles. This method leads to a calculated contrast that increases with SPIO concentration. Experimental data and a mathematical model demonstrate and characterize this diffusion-dependent, off-resonance effect. Dependence on off-resonance frequency and power are also investigated. <B>3)<I> Development of a genetic MRI marker via in vivo magnetic nanoparticle synthesis.</I></B> This work seeks to provide a gene expression marker for MRI based on bacterial magnetosomes, tiny magnets produced by naturally occurring magnetotactic bacteria. Here, <I>magA</I> is expressed in a commonly used human cell line, 293FT, resulting in the production of magnetic, iron oxide nanoparticles by these cells. MRI shows these particles can be formed <I>in vivo</I> utilizing endogenous iron and can be used to visualize cells positive for <I>magA</I>. These results demonstrate <I>magA</I> alone is sufficient to produce magnetic nanoparticles and that it is an appropriate candidate for an MRI reporter gene.
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