This proposal requests continuation funding for applications of intermolecular multiple-quantum coherences (iMQCs) for in vivo magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). iMQCs correspond to simultaneous spin flips on distant molecules in solution (the separation is selected by the strength and length of a single gradient pulse, and is typically .01-10 mm). For example, we might detect a resonance corresponding to flipping up one proton on a macromolecule, and simultaneously flipping down a proton in the water solvent (this would also be an """"""""intermolecular zero-quantum coherence"""""""" or iZQC, because the net number of spins up is unchanged). The research proposed here exploits important new developments from the current grant period. First, we have designed and demonstrated pulse sequences which simultaneously acquire up to five conventional and intermolecular multiple-quantum images, with significant advantages in signal intensity and image coregistration, and applied them to enhance contrast in breast tumors. Second, we have demonstrated the iMQC anisotropy provides a more-sensitive alternative to diffusion tensor imaging. Finally, we have demonstrated iZQC spectroscopy in vivo, with resolution enhancements. These advances will let us significantly extend the clinical utility of iMQC sequences and to create new methods for characterizing tissue and soft materials. Spectroscopic and clinical studies are closely intertwined with continued development of the theoretical framework, but the general objective is demonstration of the utility of iMQCs for the broadest possible range of imaging applications. For example, we expect to provide improved charactization of breast tumors and of traumatic brain injury, and enhanced measurement of local metabolite concentrations.
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