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

基本信息

批准号：
7010874
负责人：
LUCIO FRYDMAN
金额：
$ 10.55万
依托单位：
WEIZMANN INSTITUTE OF SCIENCE
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-02-01 至 2008-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7010874
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

项目摘要

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）：就揭开分子系统性质的适用性而言，很少有分析技术可以与多维核磁共振（NMR）的范围和能力媲美。无论是处理新药物的发现，蛋白质或核酸的结构和动力学的研究，对脑代谢的非侵入性监测还是疾病的特征，在科学领域中，几乎没有任何纪律在没有某种形式的多维NMR或MRI分析的情况下进行。然而，一个重要的缺点会影响多维NMR技术。也就是说，与其他光谱方法相比，它们需要相对较长的测量时间，这与数百或数千张扫描有关。这将某些类型的快速变化的系统（例如蛋白质变化构象变化，分析物都流过色谱柱，或在其研究领域之外的生理条件下不稳定的生物大分子。同样不适合这种相对缓慢的分析形式的是，数千种药理学化合物目前可以通过单个组合化学化学分析提供，以及混合成像/光谱技术，其中多维光谱相关与空间定位的体内方法相结合。作为本项目的一部分，我们计划制定一系列新方案，这些方案应在一次连续扫描中获得多维NMR光谱。我们寻求在现代高场NMR和MRI仪器上实施此类实验，从而为以相对较低的浓度表征分析物提供开放资源。因此，此类研究的一个重要目标将集中于缓解磁场涡流对光谱引起的效果的效果，当在两个宽孔成像系统上以及对高温冷却的探针头上以及在两个宽孔成像系统上以及对高温冷却的探头时，我们已经确定在观察到的伪影中起着重要作用。该项目的另一个目标是超快多维和核超极化NMR方法的组合。最后，在高度不均匀或不稳定的磁场上，还将利用超快NMR的原理记录单扫描1D和2D NMR光谱。反过来，这可能会打开使用非前瞻性的高田杂交磁铁来进行生物分子研究，从而能够开发出NMR系统（例如NMR系统）的经济台面，并在体内磁共振光谱范围内对相对异质性的器官进行了启用。 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.