Intermolecular Multiple-Quantum Coherence Effects in NMR

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DESCRIPTION (provided by applicant): This proposal requests continuation funding for applications of intermolecular multiple-quantum coherences (iMQCs) in nuclear magnetic resonance spectroscopy (NMR), in vivo magnetic resonance imaging (MRI) and magnetic resonance spectroscopy(MRS). iMQCs, which correspond to simultaneous spin flips on separated molecules in solution (separations of 10 um-l0 mm are typical), should be unobservable according to the conventional theoretical framework of NMR; yet over the last few years, Dr. Warren has experimentally generated iMQCs with signals nearly as large as the conventional magnetization, theoretically described this complex phenomenon, and developed useful applications. For example, Dr. Warren has shown that iMQC imaging gives tumor enhancement in rat brains and novel contrast in human brain imaging (including functional activation), with acceptable sensitivity at fields as low at 1.5 Tesla. Other demonstrated applications include elimination of inhomogeneous broadening without removal of chemical shift differences, spatially localized MRS (without susceptibility broadening and shimming artifacts which limit current applications of this technique for tumor detection and grading), and heteronuclear magnetization transfer between solute and solvent peaks. Clinical applications in the next grant period include refinement of iMQC imaging methods (contrast optimization, introduction of flow compensation and presaturation), functional MRI studies on the new 3 Tesla MRI at Princeton to validate the BOLD mechanism and determine sub-voxel activation structure, and a variety of applications of spatially localized in vivo iMQC imaging. Dr. Warren proposes to do high resolution 1066 MHz NMR of macromolecules using existing magnets which give inhomogeneous fields (and removing the inhomogeneity with iMQCs) to determine the potential value of ultrahigh field NMR for protein studies. Dr. Warren also proposes to extend his work on detection of magnetization fluctuations with dipolar fields, which could evolve into another unique contrast mechanism in imaging, and which could totally transform the way low-gamma or low-concentration species are detected in NMR.