ULTRAFAST MULTIDIMENSIONAL NMR: A NEW BIOMEDICAL TOOL

超快多维核磁共振：一种新的生物医学工具

• 批准号: 6848968
• 负责人: LUCIO FRYDMAN
• 金额: $ 10.8万
• 依托单位: WEIZMANN INSTITUTE OF SCIENCE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6848968
• 关键词: bioimaging /biomedical imaging; cryoscience; electronic spectra; high throughput technology; image enhancement; magnetic field; magnetic resonance imaging; method development; nuclear magnetic resonance spectroscopy; protein structure function; time resolved data

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：就揭示分子系统性质的适用性而言，很少有分析技术能够与多维核磁共振（NMR）的范围和能力相媲美。无论是新药物的发现，蛋白质或核酸结构和动力学的研究，脑代谢的非侵入性监测还是疾病的表征，当今科学领域几乎没有任何学科在没有多维NMR或MRI分析的帮助下进行。然而，一个重要的缺点影响多维NMR技术;即，与其他光谱方法相比，它们需要相对较长的测量时间，与数百或数千次扫描的收集相关。这使得某些快速变化的系统，如蛋白质改变构象，分析物流过色谱柱，或在生理条件下不稳定的生物大分子，不在其研究范围内。同样不适合这种相对缓慢的分析形式的是，目前可以通过单一的组合化学分析以及混合成像/光谱技术，其中多维光谱相关性与体内空间定位方法相结合，获得数千种药理学化合物。作为本项目的一部分，我们计划开发一系列新的计划，应使多维NMR光谱在一个单一的连续扫描的收购。我们试图在现代高场NMR和MRI仪器上实现这样的实验，从而为在相对低的浓度下表征分析物提供开放的资源。因此，这样的研究的一个重要目标将集中在缓解磁场涡流，我们已经确定发挥重要作用，在超快多维NMR实验时观察到的文物进行两个widebore成像系统，以及低温冷却探头上的频谱上引起的影响。该项目的另一个目标是将超快多维和核超极化NMR方法相结合。最后，超快NMR的基本原理也将被用来在高度不均匀或不稳定的磁场中记录单扫描1D和2D NMR光谱。反过来，这可以打开使用前所未有的高场混合磁体的生物分子研究，使经济的台式核磁共振系统的发展，以及使在相对异质性器官的体内磁共振光谱研究。总的来说，我们期望，通过帮助缩短任何多维光谱或成像实验的采集时间几个数量级，并通过使低分辨率磁体中的高分辨率NMR光谱的采集成为可能，该项目将有助于在所有研究领域中取得重要进展，这些领域以这样或那样的方式，迄今为止一直受益于NMR和MRI光谱学的成果。