Utilization of TMV-TEMPO as an in Vivo MRI Sensor of ROS Production in Liver Inflammation and as a DNP Agent

Magnetic resonance imaging (MRI) is a powerful tool that can noninvasively generate exquisite images of soft tissues in living subjects for medical diagnostics. This PhD dissertation details the i) utility of a nitroxyl-modified tobacco mosaic virus (TMV) as an in vivo MRI contrast agent for detection of reactive oxygen species (ROS) in murine model of liver inflammation and ii) its feasibility as an agent in MRI signal-enhancing dynamic nuclear polarization (DNP) technology. Chapter 1 entails discussion of the basics of magnetic resonance and hyperpolarization. Chapter 2 involves discussion of the identification and physical characterization of spontaneous mutation of TMV in a laboratory environment. Chapter 3 shows the successful utility of reduced TMV- TEMPO as an in vivo T2 -weighted MRI sensor of ROS in lipopolysaccharide (LPS)-induced liver inflammation in Balb/c mice. Chapter 4 details the 13 C DNP testing of TMV-TEMPO as a polarizing agent and the use of gadolinium coordination polymer GduDEP as a 13 C DNP signal enhancer. Finally, the overall conclusion and outlook of these projects are detailed in Chapter 5. Overall, this PhD dissertation ties up the experimental details and discussions of a new in vivo MRI biosensor for ROS at least in the pre-clinical level, along with some details on improving the 13 C DNP signals.