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151433 https://hdl.handle.net/2286/R.I.15999 http://rightsstatements.org/vocab/InC/1.0/ All Rights Reserved 2012 2014-12-01T00:18:59 xi, 132 p. : ill. (some col.) Doctoral Dissertation Academic theses Text eng Clavijo Jordan, Maria Veronica Bennett, Kevin M Kodibagkar, Vikram Sherry, A Dean Wang, Xiao Yarger, Jeffery Arizona State University Partial requirement for: Ph.D., Arizona State University, 2012 Includes bibliographical references (p. 113-123) Field of study: Bioengineering Sensitivity is a fundamental challenge for in vivo molecular magnetic resonance imaging (MRI). Here, I improve the sensitivity of metal nanoparticle contrast agents by strategically incorporating pure and doped metal oxides in the nanoparticle core, forming a soluble, monodisperse, contrast agent with adjustable T2 or T1 relaxivity (r2 or r1). I first developed a simplified technique to incorporate iron oxides in apoferritin to form "magnetoferritin" for nM-level detection with T2- and T2* weighting. I then explored whether the crystal could be chemically modified to form a particle with high r1. I first adsorbed Mn2+ ions to metal binding sites in the apoferritin pores. The strategic placement of metal ions near sites of water exchange and within the crystal oxide enhance r1, suggesting a mechanism for increasing relaxivity in porous nanoparticle agents. However, the Mn2+ addition was only possible when the particle was simultaneously filled with an iron oxide, resulting in a particle with a high r1 but also a high r2 and making them undetectable with conventional T1-weighting techniques. To solve this problem and decrease the particle r2 for more sensitive detection, I chemically doped the nanoparticles with tungsten to form a disordered W-Fe oxide composite in the apoferritin core. This configuration formed a particle with a r1 of 4,870mM-1s-1 and r2 of 9,076mM-1s-1. These relaxivities allowed the detection of concentrations ranging from 20nM - 400nM in vivo, both passively injected and targeted to the kidney glomerulus. I further developed an MRI acquisition technique to distinguish particles based on r2/r1, and show that three nanoparticles of similar size can be distinguished in vitro and in vivo with MRI. This work forms the basis for a new, highly flexible inorganic approach to design nanoparticle contrast agents for molecular MRI. Biomedical Engineering Biophysics Apoferritin Manganese MRI Tungsten Nanostructured materials Magnetic resonance imaging Contrast media (Diagnostic imaging) Design of apoferritin-based nanoparticle MRI contrast agents through controlled metal deposition