Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM042208-03
Application #
3300729
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1990-08-01
Project End
1995-07-31
Budget Start
1992-08-01
Budget End
1993-07-31
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
University of Illinois Urbana-Champaign
Department
Type
Schools of Medicine
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820

  Publications

Kinrade, S D; Schach, A S; Hamilton, R J et al. (2001) NMR evidence of pentaoxo organosilicon complexes in dilute neutral aqueous silicate solutions. Chem Commun (Camb) :1564-5
Knight, C T; Kinrade, S D (1999) Silicon-29 nuclear magnetic resonance spectroscopy detection limits. Anal Chem 71:265-7
Kinrade, S D; Del Nin, J W; Schach, A S et al. (1999) Stable five- and six-coordinated silicate anions in aqueous solution. Science 285:1542-5
Smirnova, T I; Smirnov, A I; Belford, R L et al. (1999) Interaction of Gd(III) MRI contrast agents with membranes: a review of recent EPR studies. MAGMA 8:214-29
Norby, S W; Swartz, H M; Clarkson, R B (1998) Electron and light microscopy studies on particulate EPR spin probes lithium phthalocyanine, fusinite and synthetic chars. J Microsc 192:172-85
Clarkson, R B; Odintsov, B M; Ceroke, P J et al. (1998) Electron paramagnetic resonance and dynamic nuclear polarization of char suspensions: surface science and oximetry. Phys Med Biol 43:1907-20
Smirnova, T I; Smirnov, A I; Belford, R L et al. (1997) Interaction of MRI gadolinium contrast agents with phospholipid bilayers as studied by 95 GHz EPR. Acta Chem Scand 51:562-6
Norby, S W; Weyhenmeyer, J A; Clarkson, R B (1997) Stimulation and inhibition of nitric oxide production in macrophages and neural cells as observed by spin trapping. Free Radic Biol Med 22:1-9
Clarkson, R B; Norby, S W; Smirnov, A et al. (1995) Direct measurement of the accumulation and mitochondrial conversion of nitric oxide within Chinese hamster ovary cells using an intracellular electron paramagnetic resonance technique. Biochim Biophys Acta 1243:496-502
Vahidi, N; Clarkson, R B; Liu, K J et al. (1994) In vivo and in vitro EPR oximetry with fusinite: a new coal-derived, particulate EPR probe. Magn Reson Med 31:139-46

Showing the most recent 10 out of 13 publications