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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).

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.
ContributorsClavijo Jordan, Maria Veronica (Author) / Bennett, Kevin M (Thesis advisor) / Kodibagkar, Vikram (Committee member) / Sherry, A Dean (Committee member) / Wang, Xiao (Committee member) / Yarger, Jeffery (Committee member) / Arizona State University (Publisher)
Created2012
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Leonard Hayflick studied the processes by which cells age during the twentieth and twenty-first centuries in the United States. In 1961 at the Wistar Institute in the US, Hayflick researched a phenomenon later called the Hayflick Limit, or the claim that normal human cells can only divide forty to sixty

Leonard Hayflick studied the processes by which cells age during the twentieth and twenty-first centuries in the United States. In 1961 at the Wistar Institute in the US, Hayflick researched a phenomenon later called the Hayflick Limit, or the claim that normal human cells can only divide forty to sixty times before they cannot divide any further. Researchers later found that the cause of the Hayflick Limit is the shortening of telomeres, or portions of DNA at the ends of chromosomes that slowly degrade as cells replicate. Hayflick used his research on normal embryonic cells to develop a vaccine for polio, and from HayflickÕs published directions, scientists developed vaccines for rubella, rabies, adenovirus, measles, chickenpox and shingles.

Created2014-07-20
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Although best known for his work with the fruit fly, for which he earned a Nobel Prize and the title "The Father of Genetics," Thomas Hunt Morgan's contributions to biology reach far beyond genetics. His research explored questions in embryology, regeneration, evolution, and heredity, using a variety of approaches.

Created2007-09-25
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Created1935