Graduate and Postdoctoral Studies
In Vivo Molecular Magnetic Resonance Imaging via Hyperpolarized Silicon Particles
Wednesday, July 12, 2017
to 10:30 AM
285 BioScience Research Collaborative
This thesis describes the characterization, development and application of hyperpolarized silicon particles, which can serve as a molecular imaging platform based on magnetic resonance imaging (MRI). Silicon particles are suited for use as biomedical imaging agents due to their biocompatibility, biodegradability, and relatively simple surface chemistry that facilitates drug loading and functionalization for targeting various diseases as well as physiological processes. A method of hyperpolarizing the 29Si nuclei inside silicon particles using dynamic nuclear polarization (DNP) has recently been developed, increasing the MR signal by several orders-of-magnitude through enhanced nuclear spin alignment. At room temperature, enhanced spin polarization of 29Si nuclei lasts on the order of tens of minutes, significantly longer than that of other hyperpolarized species (tens of seconds). In addition to extremely long-lived signal, hyperpolarized silicon particles provide background-free positive contrast, thereby making a wide range of imaging applications possible.
For silicon particles on the micrometer scale, we first explored their application for MRI-guided catheter tracking, demonstrating catheter tip tracking in 2D, 3D and in vivo over extended period of time without the use of ionizing radiation. Paving way for potential targeted molecular imaging applications, we characterized silicon particles of various sizes (20 nm to 2µm), whose hyperpolarized signal were found to have characteristic spin relaxation times (T1) ranging from ~10 to 50 mins. The addition of various functional groups to the particle surface had no effect on the hyperpolarized signal buildup or decay rates and allowed in vivo imaging over long time scales. Additional in vivo studies examined a variety of particle administration routes in mice, including intraperitoneal injection, rectal enema, and oral gavage. Targeting moieties such as antibodies were found to be able to retain their functionalities after enduring the harsh DNP condition of low temperature (several Kelvins) and continuous microwave irradiation. As a proof of concept study, we demonstrated targeted imaging of colorectal cancer in genetic models using hyperpolarized silicon particles functionalized with MUC1 antibodies.
To better hyperpolarize silicon particles on the nanometer scale, we incorporated external radicals such as TEMPO to eliminate the bottleneck of insufficient surface electrons and calibrated the concentration of radicals needed to achieve better signal enhancement for various particle sizes (20-200 nm). With optimal amounts of the added radicals, 29Si T1 times are ~20 minutes and MR imaging in phantoms can be achieved over an hour after completion of hyperpolarization.
Equipped with the unusually long signal decay time and the fact that the signal decay times are not affected by surface functionalization or the in vivo environment, hyperpolarized silicon particles have the potential of becoming the next generation high-impact molecular MR imaging agents.