In terms of applicability to unravel the nature of molecular systems, few analytical techniques can rival the range and capabilities of multidimensional nuclear magnetic resonance (NMR). Whether dealing with the discovery of new pharmaceutical drugs, the investigation of protein or nucleic acid structure and dynamics, the non-invasive monitoring of brain metabolism or the characterization of disease, hardly any discipline in the realm of science proceeds nowadays without the aid of some form of multidimensional NMR or MRI analysis. Yet one important drawback affects multidimensional NMR techniques; namely, that by contrast to other spectroscopic methods, they require relatively long measurement times, associated with the collection of hundreds or thousands of scans. This places certain kinds of rapidly changing systems, like proteins changing conformation, analytes flowing through a chromatography column, or biological macromolecules that are unstable under physiological conditions, outside its realm of study. Also unsuitable to this relatively slow form of analysis are the thousands of pharmacological compounds that can currently be made available by a single combinatorial-chemistry assay, as well as hybrid imaging/spectroscopy techniques, where multidimensional spectral correlations are combined with in vivo methods of spatial localization. As part of the present project, we plan to develop a series of new schemes that should enable the acquisition of multidimensional NMR spectra within a single continuous scan. We seek to implement such experiments on modern high-field NMR and MRI instrumentation, thus providing an open resource for characterizing analytes at relatively low concentrations. An important goal of such research will thus concentrate on relieving the effects induced on the spectra by magnetic field eddy currents, which we have identified as playing an important role in the artifacts observed when ultrafast multidimensional NMR experiments are carried out on both widebore imaging systems, as well as on cryogenically cooled probeheads. Another goal of this project will be the combination of ultrafast multidimensional and nuclear hyperpolarization NMR methods. Finally, the principles underlying ultrafast NMR will also be exploited to record single-scan 1D and 2D NMR spectra on highly inhomogeneous or unstable magnetic fields. This could, in turn, open up the use of unprecedently high-field hybrid magnets to biomolecular investigations, enable the development of economic bench-top like NMR systems, as well as enable in vivo magnetic resonance spectroscopy investigations on relatively heterogeneous organs. Overall, we expect that, by helping to shorten the acquisition time of any multidimensional spectroscopy or imaging experiment by several orders of magnitude, and by enabling the acquisition of high-resolution NMR spectra in low resolution magnets, this project will help usher in important advances into all research areas that, in one way or another, have hitherto been benefiting from the fruits of NMR and MRI spectroscopies.
