11.74T/210 Millimeter NMR Magnet System/In VivO MRS/MRI

我们申请500,000美元，用于购买MagneX 11.74T/21厘米水平孔磁体，用于开发先进的磁共振(MR)波谱(MRS)和成像(MRI)系统，用于研究转基因小鼠和大鼠模型。计划在11.74T系统上进行的研究的主要目的是建立体内代谢和生理的MRS和MRI测量，并应用这些方法来了解关键基因产物在转基因小鼠和大鼠模型中的功能。耶鲁大学的MR小组由道格拉斯·L·罗斯曼博士领导，他是这项建议的负责人，在开发MRS/MRI方法研究小动物和人类的新陈代谢方面一直处于领先地位。SIG的主要用户组由8名NIH资助的耶鲁大学研究人员组成，他们将使用11.74T解决与人类疾病相关的基本问题，包括转基因糖尿病模型中肌肉和肝脏碳水化合物及脂肪代谢的分子调控；谷氨酸和γ-氨基丁酸释放和循环的调控；谷氨酸神经递质循环到神经能量学的分子机制；功能磁共振成像的神经生理学基础；哺乳动物感觉系统(如胡须桶皮质和嗅球)的功能神经解剖学。耶鲁大学磁共振中心(MRC)活跃的人类磁共振研究项目的存在，促进了将这些发现转化为糖尿病、癫痫、新生儿缺氧、肥胖和精神疾病的临床研究。这些研究都依赖于耶鲁大学医学研究中心的定量高分辨率MRS和MRI方法的发展，这是由最先进的磁铁技术实现的。美国国立卫生研究院最近批准耶鲁大学开发转基因小鼠代谢表型中心，强调了进一步开发啮齿动物MRS/MRI技术的重要性，11.74T系统对此至关重要。该中心是一个全国性的资源，为全国各地的NIH资助的研究人员提供糖尿病转基因小鼠模型，耶鲁大学开发的先进的MRS和MRI方法。这项工作将广泛使用11.74T系统。我们相信，耶鲁大学在MRS/MRI测量方面的长期创新传统和密切的跨学科合作为11.74T体内MRS/MRI系统的开发和转基因小鼠和其他小动物模型的应用提供了理想的场所，以了解健康和疾病中代谢和生理的分子控制。

We are submitting a request for $500,000 towards the purchase of a Magnex 11.74T/21 cm horizontal bore magnet for the development of an advanced magnetic resonance (MR) spectroscopy (MRS) and imaging (MRI) system for studying transgenic mice and rat models. The major aims of the research planned on the 11.74T system are to develop in vivo MRS and MRI measurements of metabolism and physiology, and apply these methods to understand the function of key gene products in transgenic mouse and rat models. The MR group at Yale, directed by Dr. Douglas L. Rothman who is the PI o this proposal, has been a leader in the development of MRS/MRI methods for studying metabolism in small animals and humans. The primary user group of the SIG consists of 8 NIH funded Yale investigators who will use the 11.74T to address fundamental questions relevant to human disease including the molecular regulation of muscle and liver carbohydrate and lipid metabolism in transgenic models of diabetes; the regulation of neurotransmitter glutamate and gamma-amino butyric acid release and recycling; the molecular mechanisms coupling glutamate neurotransmitter cycling to neuroenergetics; the neurophysiological basis of fMRI, and the functional neuroanatomy of mammalian sensory systems (e.g., whisker barrel cortex and olfactory bulb). The presence of an active human MR research program at the Magnetic Resonance Center (MRC) at Yale has facilitated the translation of these findings to clinical research studies in diabetes, epilepsy, neonatal hypoxia, obesity, and psychiatric disorders. These studies all have depended upon the development of quantitative high resolution MRS and MRI methods at the Yale MRC, made possible by state-of-the-art magnet technology. The importance of the further development of rodent MRS/MRI technology, for which the 11.74T system is critical, is emphasized by the recent approval of an award to Yale from the NIH to develop a transgenic Mouse Metabolic Phenotyping Center. This Center is a national resource which makes available to NIH funded investigators throughout the country with transgenic mouse models of diabetes the advanced MRS and MRI methods developed at Yale. This effort will make extensive use of the 11.74T system. We believe the long-standing tradition at Yale of innovation in MRS/MRI measurements and close interdisciplinary collaborations provide an ideal site for the development of an 11.74T in vivo MRS/MRI system and the application to transgenic mouse and other small animal models for understanding the molecular control of metabolism and physiology in health and disease.