Hyperpolarized Silicon Particles as In-vivo Imaging Agents

Abstract

This thesis describes the development of hyperpolarized silicon particles as a new type of magnetic resonance imaging (MRI) agent. Silicon particles are inexpensive, non-toxic, biodegradable, targetable, and have unique physical properties that lead to extremely long nuclear polarization times. The \(^{29}Si\) nuclei are hyperpolarized by low temperature dynamic nuclear polarization using naturally occurring defects at the particle surface and directly imaged using \(^{29}Si\) MRI. The imaging window achievable is several orders of magnitude longer than other hyperpolarized imaging agents. The technique requires no additional imaging agent to be incorporated into the silicon, and so toxicity complications are reduced. The construction of a system for low temperature dynamic nuclear polarization and a NMR spectrometer for studying the nuclear polarization dynamics in silicon particles is described. Room temperature nuclear spin relaxation \((T_1)\) times are investigated for a variety of silicon particles spanning five orders of magnitude in mean diameter, from 10nm nanoparticles to mm-scale granules. The nuclear \(T_1\) times of all Si particles are found to be long, ranging from many minutes to several hours at room temperature. \(T_1\) is found to be a function of particle size, dopant concentration, synthesis method and crystallinity. A core-shell model to describe the electron and nuclear spin dynamics in the particles is developed. The decay in nuclear hyperpolarization is studied as a function of ambient magnetic field and temperature, demonstrating that the long spin relaxation times persist despite changing environmental conditions. A new technique is reported for enhancing the dynamic nuclear polarization in silicon particles using modulated microwave irradiation. A theoretical model for understanding this enhanced polarization process is developed. As well as providing an efficient mechanism for polarizing the \(^{29}Si\) nuclei within the particle, the surface defects are also found to be efficient at polarizing \(^1H\) nuclei in frozen solutions surrounding the particles. Several in-vivo applications of hyperpolarized \(^{29}Si\) MRI are demonstrated, including gastrointestinal imaging, intravenous imaging and mapping blood flow in a tumor. The spin relaxation rates are found to be unaffected by surface functionalization, the particles tumbling in solution, or the in-vivo environment.