HyperSense System for Molecular Imaging

描述（由申请人提供）：宾夕法尼亚大学寻求获得用于增强异核磁化的HyperSense仪器。Oxford Instruments制造的HyperSense是一种在磁共振实验之前使用动态核极化（DNP）来增加样品磁化的仪器。使用该系统，可以将1D NMR光谱的信噪比放大高达10，000倍。由于这种非凡的信噪比增强，该产品开辟了定性的新研究领域，可能彻底改变常规NMR光谱学领域。此外，可以直接将此概念及其潜力外推到MR成像。这种独特的模块化仪器可以与任何当前的常规NMR系统一起使用，以产生用于液态NMR的偏振增强样品。然后，以这种方式获得的样品可携带到MRI应用中。具有中心能量代谢、信号传导和生物合成作用的各种靶分子已经通过DNP技术成功地超极化。拟议中的仪器将促进生理学、癌症和糖尿病的基础研究。HyperSense偏振器是一种通用仪器，可用于分析许多其他重要化合物，如脂肪酸和氨基酸。该仪器100%用于研究，将由宾夕法尼亚大学、费城儿童医院、福克斯蔡斯癌症中心和托马斯杰斐逊大学的研究人员使用。它将显著增强10个主要用户项目，主要研究者得到23个NIH赠款。这十个项目包括：（i）评估15 N标记的化合物作为肺灌注和炎症的示踪剂，（ii）研究苯乙酸和苯丁酸在癌细胞中的代谢，旨在了解这两种化合物如何抑制癌症增殖，（iii）研究胰腺β细胞，以进一步了解它们在糖尿病中的作用，（iv）体外测量人神经胶质瘤细胞中的代谢途径，目的是了解能够使细胞快速增殖的变化，（v）研究超极化铵作为谷氨酰胺合成酶活性探针的潜力，（vi）关于使用超极化示踪剂在鼠模型中检测卵巢癌的可行性研究，（vii）评价超极化示踪剂是否可用于鉴定小鼠中的胰腺癌异种移植物，（viii）测量健康和有缺陷的鼠和人胰岛细胞中的TCA循环通量，（ix）使用大鼠模型的研究，的方法，使人类黑色素瘤敏感的热疗和化疗，和（x）的倡议支持的小动物成像资源（SAIR）在宾夕法尼亚大学。 公共卫生相关性：超极化碳-13磁共振成像和光谱学有可能以前所未有的灵敏度揭示健康和患病器官的代谢过程。重要的临床应用包括肿瘤和其他癌细胞的诊断，对治疗反应的更快速监测，以及对糖尿病和其他生理疾病的研究。

DESCRIPTION (provided by applicant): The University of Pennsylvania seeks to acquire a HyperSense instrument for enhancing the magnetization of heteronuclei. HyperSense, manufactured by Oxford Instruments, is an instrument which uses Dynamic Nuclear Polarization (DNP) to increase the magnetization of a sample prior to a magnetic resonance experiment. Using this system, it is possible to amplify the signal-to-noise ratio of 1D NMR spectra by a factor of up to 10,000. Due to this extraordinary signal-to-noise enhancement, this product opens up qualitatively new areas of research, potentially revolutionizing the field of routine NMR spectroscopy. Furthermore, it is straightforward to extrapolate this concept and its potential to MR imaging. This unique and modular instrument may be used with any current conventional NMR system to produce polarization-enhanced samples for liquid state NMR. The samples obtained in this fashion are then portable to MRI applications. A variety of target molecules with central energy metabolism, signaling, and biosynthesis roles have been successfully hyperpolarized through the DNP technique. The proposed instrument will facilitate basic research in physiology, cancer, and diabetes. The HyperSense polarizer is a general purpose instrument and could be used to polarize many other important compounds such as fatty acids and amino acids. The proposed instrument is dedicated 100% to research, and it will be used by investigators from the University of Pennsylvania, Children's Hospital of Philadelphia, Fox Chase Cancer Center, and Thomas Jefferson University. It will significantly enhance ten major user programs with Principal Investigators who are supported by twenty-three NIH grants. The ten programs include (i) evaluation of 15N-labeled compounds as tracers of pulmonary perfusion and inflammation, (ii) a study of metabolism of phenylacetate and phenylbutyrate in cancer cells aimed at understanding how these two compounds inhibit cancer proliferation, (iii) a study of pancreatic beta cells to further understand their role in diabetes, (iv) in vitro measurements of metabolic pathways in human glioma cells with the goal of understanding the changes which enable rapid cell proliferation, (v) a study of the potential of hyperpolarized ammonium as a probe of glutamine synthetase activity, (vi) a feasibility study concerning the use of hyperpolarized tracers to detect ovarian cancer in a murine model, (vii) evaluation of whether hyperpolarized tracers may be used to identify pancreatic cancer xenografts in mice, (viii) measurements of the TCA cycle flux in healthy and defective murine and human islet cells, (ix) a study, using a rat model, of methods for sensitizing human melanoma to hyperthermia and chemotherapy, and (x) the initiatives supported by the Small-Animal Imaging Resource (SAIR) at the University of Pennsylvania. PUBLIC HEALTH RELEVANCE: Hyperpolarized carbon-13 MR imaging and spectroscopy have the potential to reveal metabolic processes in healthy and diseased organs with an unprecedented sensitivity. Important clinical applications include diagnosis of tumors and other cancer cells, more rapid monitoring of response to therapy, and research into diabetes and other physiological disorders.