Development of Advanced Molecular Imaging Probes and Contrasts for Magnetic Resonance Imaging

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Molecular imaging is a non-invasive tool for visualization of cellular function in living organisms. For magnetic resonance imaging (MRI), cellular function is imaged by injecting a contrast agent into an organism that produces quantifiable changes in the image reflecting variations in metabolic function. These compounds may be designed to bind preferentially to a specific protein or be metabolized directly by cells so that the effects of their biodistribution can be imaged using MRI. Compared with other imaging modalities, the intrinsic sensitivity of MRI is low and the challenge is to produce newer contrast agents that can be effective at lower concentrations. The chief property affecting sensitivity is the contrast agent "relaxivity" - the effectiveness of an agent to cause signal enhancement through increased magnetic relaxation of nearby tissue. The relaxivity of targeted contrast agents is greatly enhanced when the agent is in its bound state and its relaxivity is highly dependent on the magnetic field. This characteristic is exploited in a novel form of MRI contrast, which we have developed called dreMR that greatly increases the effective target specificity by producing a contrast that is proportional to the concentration of only bound agent. We are also studying the relaxation of a new type of agent based on hyperpolarized 13C-enriched endogenous compounds. These slowly relaxing agents are highly magnetized (hyperpolarized) in vitro and then are injected into an animal model and spectroscopically imaged along with their metabolic products. The spatial distributions of the metabolites yield valuable information about in vivo cellular processes. The objectives of this Discovery Grant are three-fold: 1) measure relaxivity profiles of novel contrast agents produced by collaborating chemistry groups, 2) improve the dreMR method and extend it to in vivo imaging with animal models, and 3) determine the "decay time" of the hyperpolarization state for 13C-enriched compounds and the effects of adding paramagnetic compounds to enhance hyperpolarization. This grant will provide training in MRI science for one undergraduate and two graduate students in medical physics during each year of the research program.