Hyperpolarized High Field NMR Facility For Metabolic Profiling Of Human Disease

用于人类疾病代谢分析的超极化高场核磁共振设备

• 批准号: 7388745
• 负责人: John Kurhanewicz
• 金额: $ 49.24万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-15 至 2009-02-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7388745
• 关键词: Animals; Biological Markers; Biological Models; California; Cells; Chemistry; Clinical; Coupled; Coupling; Data; Disease; Equipment; Funding; Genetic; Human; Investigation; Label; Laboratory Research; Magic; Magnetic Resonance Imaging; Measurement; Metabolic; Metabolic Pathway; Metabolism; Mission; Modeling; Molecular Analysis; NMR Spectroscopy; Nuclear; Nuclear Magnetic Resonance; Numbers; Pathologic; Pathology; Proteins; Research; Resolution; Resources; Running; Sampling; Spectrum Analysis; System; Technology; Therapeutic; Time; Tissues; Translating; United States National Institutes of Health; Universities; animal tissue; cost effective; human disease; insight; instrument; pre-clinical; programs; response; spectroscopic imaging; tissue/cell culture

DESCRIPTION (provided by applicant): This NIH shared instrument request is the key component in establishing a unique facility for hyperpolarized nuclear magnetic resonance (NMR) spectroscopy that provides a dramatic 10,000+fold improvement in sensitivity for investigating metabolic pathways and MR imaging biomarker discovery for a variety of human diseases. Funds are requested for the core component of this facility: an Oxford Instruments Biotools HyperSenseTM Dynamic Nuclear Polarizer (DNP), which is a new product first offered in the last year. This system will be combined with two existing high field 500 MHz vertical bore NMR spectrometers located in the UCSF NMR lab on the Mission Bay campus. Both magnets are dedicated to running biomedical samples and they have complimentary features, including high-resolution magic angle spinning (HR-MAS) spectroscopy capabilities, and a cryoprobe with an automatic sample changer. The UCSF NMR lab and associated research laboratory contain all of the pathology, chemistry and molecular analysis equipment required to prepare 13C labeled substrates for polarization and to correlate metabolic profiles with pathologic, genetic and protein changes for biomarker discovery. This proposal will take advantage of these extensive University of California and NIH funded resources. The unprecedented increase in sensitivity obtained from DNP polarization will permit NMR measurements previously considered impossible for studying human and animal tissue, biofluids, and pre-clinical cell and tissue culture models. Increased sensitivity will also reduce the time required for performing 1-D and 2-D NMR studies of tissues and cells. The coupling of DNP technology with high resolution NMR spectroscopy will allow the investigation of numerous hyperpolarized 13C labeled substrates, optimize their polarization and optimize the acquisition of the hyperpolarized spectroscopic data in a cost effective manner. This new facility is critical for not only developing applications that take advantage of the DNP technology in tissues and cells but also for translating the insights gained in these model systems into the ongoing pre-clinical animal and eventually clinical hyperpolarized 13C spectroscopic imaging studies being conducted at UCSF. This combination of high field NMR spectrometers with a HyperSenseTM DNP polarizer will be coupled with the large number of successful NIH-funded MR imaging research programs at UCSF and will create a unique hyperpolarized MR program that will greatly advance our understanding of the metabolism for a wide variety of diseases and result in the identification of new metabolic biomarkers of disease presence, aggressiveness and therapeutic response.

描述(由申请人提供)：这项NIH共享仪器申请是建立一个独特的超极化核磁共振(核磁共振)波谱设施的关键组成部分，该设施为研究代谢途径和发现各种人类疾病的磁共振成像生物标记物提供了10,000多倍的灵敏度。该设施的核心部件：牛津仪器生物公司HyperSenseTM动态核偏振器(DNP)是去年首次推出的新产品，需要资金。该系统将与位于观澜湾校区加州大学旧金山分校核磁共振实验室的两台现有的高场500 MHz垂直钻孔核磁共振波谱仪相结合。这两种磁铁都专门用于运行生物医学样品，它们具有互补的功能，包括高分辨率魔角旋转(HR-MAS)光谱功能，以及带有自动换样器的冷冻探头。加州大学旧金山分校的核磁共振实验室和相关研究实验室拥有所需的所有病理、化学和分子分析设备，以准备用于极化的13C标记底物，并将代谢谱与病理、遗传和蛋白质变化相关联，以发现生物标记物。这项提案将利用加州大学和美国国立卫生研究院资助的大量资源。DNP极化获得的前所未有的灵敏度增加将使以前被认为不可能用于研究人类和动物组织、生物液以及临床前细胞和组织培养模型的核磁共振测量成为可能。灵敏度的提高还将减少对组织和细胞进行一维和二维核磁共振研究所需的时间。DNP技术与高分辨率核磁共振波谱的结合将使人们能够研究大量超极化的13C标记底物，优化它们的极化，并以经济高效的方式优化超极化光谱数据的获取。这一新设施不仅对于开发在组织和细胞中利用DNP技术的应用至关重要，而且对于将在这些模型系统中获得的见解转化为正在进行的临床前动物研究以及最终在加州大学旧金山分校进行的临床超极化13C光谱成像研究也是至关重要的。 这种高场核磁共振光谱仪与HyperSenseTM DNP偏振器的结合，将与加州大学旧金山分校由美国国立卫生研究院资助的大量成功的磁共振成像研究项目相结合，将创建一个独特的超极化磁共振项目，该项目将极大地促进我们对各种疾病的新陈代谢的了解，并导致识别新的代谢生物标记物，反映疾病的存在、侵袭性和治疗反应。

项目成果

Quantitative metabolic profiles of 2nd and 3rd trimester human amniotic fluid using (1)H HR-MAS spectroscopy.

• DOI: 10.1007/s10334-009-0184-0
• 发表时间: 2009-12
• 期刊: Magma (New York, N.Y.)
• 作者: Cohn BR;Joe BN;Zhao S;Kornak J;Zhang VY;Iman R;Kurhanewicz J;Vahidi K;Yu J;Caughey AB;Swanson MG
• 通讯作者: Swanson MG