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

我们正在提交一份50万美元的申请，用于购买一个Magrex 11.74T/21 cm水平孔磁体，用于开发一个先进的磁共振（MR）光谱（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开发代谢和生理的体内MRS和MRI测量，并应用这些方法来了解转基因小鼠和大鼠模型中关键基因产物的功能。耶鲁大学的MR小组由道格拉斯L. Rothman是该提案的PI，他一直是研究小动物和人类代谢的MRS/MRI方法发展的领导者。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来解决与人类疾病相关的基本问题，包括糖尿病转基因模型中肌肉和肝脏碳水化合物和脂质代谢的分子调节;神经递质谷氨酸和γ-氨基丁酸释放和再循环的调节;将谷氨酸神经递质循环与神经能量学耦合的分子机制; fMRI的神经生理学基础，以及哺乳动物感觉系统的功能性神经解剖学（例如，须桶皮层和嗅球）。耶鲁大学磁共振中心（MRC）的一个活跃的人类MR研究项目的存在促进了这些发现在糖尿病，癫痫，新生儿缺氧，肥胖和精神疾病的临床研究中的转化。这些研究都依赖于耶鲁MRC定量高分辨率MRS和MRI方法的发展，这是由最先进的磁体技术实现的。啮齿动物MRS/MRI技术的进一步发展的重要性，其中11.74T系统是至关重要的，强调了最近批准的奖励耶鲁大学从美国国立卫生研究院开发一个转基因小鼠代谢表型中心。该中心是一个国家资源，使全国各地的NIH资助的研究人员与糖尿病转基因小鼠模型的先进MRS和MRI方法在耶鲁大学开发。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开发11.74T体内MRS/MRI系统以及应用于转基因小鼠和其他小动物模型以了解健康和疾病中代谢和生理学的分子控制提供了理想的场所。

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.