This proposal outlines a program of research designed to obtain more detailed physical information on the mode of action of paramagnetic materials that currently are being investigated as potential contrast agents in diagnostic Magnetic Resonance Imaging (MRI) procedures. All of the materials to be examined in this study are in a class of reagents acting as enhancers of nuclear spin relaxation. MRI contrast agents will be studied by EPR, NMR, and related techniques. Specifically, we will employ multi-frequency EPR and 1-2 GHz, 2-4 GHz, 9.5 GHz, 35 GHz, and 95 GHz, ENDOR at 9.5 GHz and 35 GHz, ESE at 2-4 GHz and 9.5 GHz, and oxygen-17 NMR 9at Bo = 7T) to measure parameters thought to control the relaxivity of the agents. The following key variables (or associated experimental parameters) will be examined: g, A, zero field splitting (ZFS), ZFS modulation correlation time (tauv), electron spin relaxation times (T1e and T2e), rotational correlation time (tauR), water exchange rate (or dwell time, tauM), and the number (q) and average distance (r) of waters in the near-neighbor solvation shells of the paramagnetic materials. Using such detailed information, we will assess the relaxivity of MRI agents int he light of current theories. Nuclear Magnetic Resonance Dispersion (NMRD) data also will be obtained (with a Koenig relaxometer) and interpreted with the aid of the other physical measurements mentioned above. Contrast agents based on paramagnetic metal ions, especially Gd(III) and Mn(II), will be the most intensively investigated in the program. Special attention will be paid to changes in the relaxivity of agents and changes in structure brought about by complexation of the agents with chelates and macromolecules. Predictions based on the results will guide synthesis of new agents; their effectiveness will be tested by the same procedures. Through this study, information useful in designing more effective contrast agents for diagnostic magnetic resonance imaging of human patients will be obtained.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Diagnostic Radiology Study Section (RNM)
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University of Illinois Urbana-Champaign
Schools of Medicine
United States
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