Adiabatic pulse preparation for imaging iron oxide nanoparticles
Harris, Steven Scott
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Iron oxide nanoparticles are of great interest as contrast agents for research and potentially clinical molecular magnetic resonance imaging (MRI). Biochemically modifying the surface coatings of the particles with proteins and polysaccharides enhances their utility by improving cell receptor specificity, increasing uptake for cell labeling and adding therapeutic molecules. Together with the high contrast they produce in MR images, these characteristics promise an expanding role for iron oxide nanoparticles and molecular MR imaging for studying, diagnosing and treating diseases at the molecular level. However, these contrast agents produce areas of signal loss with traditional MRI sequences that are not specific to the nanoparticles and cannot easily quantify the contrast agent concentration. With the expanding role of iron oxide nanoparticles in molecular imaging, new methods are needed to produce a quantitative contrast that is specific to the iron oxide nanoparticle. This dissertation presents a new method for detecting and quantifying iron oxide nanoparticles using an adiabatic preparation pulse and the failure of the adiabatic condition for spins diffusing near the particles. In the first aim, the theoretical foundation of the work is presented, and a Monte Carlo simulation supporting the proposed mechanism of the contrast is described. Adiabatic pulse prepared imaging sequences are also developed for imaging at 3 Tesla and 9.4 Tesla to highlight the translational potential of the approach for clinical examinations and scientific research, and the linear correlation of the contrast with iron concentration ideal for quantification is presented. Further, the physical characteristics of the nanoparticles and the parameters of the MRI sequence are modified to characterize the approach. In the second aim, the contrast is characterized in more realistic phantoms and in vitro, and a method to more accurately quantify nanoparticle concentration in the presence of magnetization transfer is presented. Finally, accelerated imaging methods are implemented to acquire the adiabatic contrast in a time compatible with in vivo imaging, and the technique is evaluated in an in vivo model of quantitative iron oxide nanoparticle imaging. Together, these aims present a method using an adiabatic preparation pulse to generate an MR contrast based on the microscopic magnetic field gradients surrounding the iron oxide nanoparticles that is suitable for in vivo quantitative, molecular imaging.