Development of Novel Molecular Imaging Agents and Methods for Magnetic Resonance Imaging

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The central goal of this research is the development of molecular imaging methods and agents for use with magnetic resonance imaging (MRI). Molecular imaging is a research discipline, which seeks to non-invasively visualize, characterize and quantify processes taking place at the molecular or cellular level in living organisms. Since MRI is already the standard of care in many diseases, there is great interest in developing new agents and methods for MRI to image molecular processes in vivo. MRI produces excellent images of tissue with high contrast and resolution. It is also capable of providing “functional” information, which can provide important context for understanding molecular imaging data. Unfortunately it is often difficult to detect molecular “targets” using MRI due to their low in vivo concentration and the limited sensitivity of MRI. The research proposed in this Discovery Grant is focused on developing new molecular imaging agents and methods with high target sensitivity and specificity for use with MRI. There are three general research objectives to support this research goal.*** Our first research objective is the characterization of new contrast agents using relaxometry. Many contrast agents for MRI are based on paramagnetic compounds, which increase the relaxation of nearby tissue. The effectiveness of these agents is characterized by their relaxivity. This is measured in a series of experiments known as Nuclear Magnetic Relaxation Dispersion (NMRD) measurements. We will collaborate with contrast agent chemistry groups developing new MRI agents, providing them NMRD data, which can be used to engineer next-generation agents. In addition, we are developing a fast magnetic field-cycling method for MRI known as dreMR, which can be used to improve the “specificity” of targeted contrast agents for molecular imaging.***In addition to protons, other nuclei can be used with MRI to determine important information about the cellular environment. We are interested in in vivo imaging of sodium and carbon-13 nuclei with MRI, which can reveal important information about biochemical processes in cells. This requires development of special software (known as pulse sequences) and RF hardware for MRI. Efficient pulse sequences and RF hardware will increase the sensitivity of MRI so that we can reduce our image acquisition time and improve the spatial resolution of our images. *** Our final objective is the development of a reporter-gene and probe system for magnetic resonance and bioluminescence imaging modalities. MRI reporter/probe systems can be used for tracking the location and fate of implanted cells. MRI reporters have excellent image resolution and tissue penetration but lack sensitivity compared to bioluminescence reporters. We will use genome-editing methods to add sensitive BLI and MRI reporter genes to cell lines, which will enable improved cell tracking experiments in animals.