Acquisition of a Bruker 11.7T/16cm Preclinical Scanner for Novel MRI/MRSI Studies

转基因啮齿动物是研究糖尿病发病机制和治疗的最重要的翻译模型。 疾病。然而，磁共振成像(MRI)和波谱(MRS)以及光谱 转基因小鼠和最近转基因大鼠的成像(MRSI)研究由于没有 足够的空间分辨率来区分关键的解剖结构，如皮质柱和皮质层。使用 利用低温技术提高灵敏度的超高场动物磁共振系统的研制 增强，有独特的机会打破这一敏感性障碍，允许超高分辨率 转基因模型中的功能、结构和代谢3D脑成像，可直接转化为 人体研究。这项提议的主要目标是安装和开发最先进的 耶鲁大学核磁共振超高频布鲁克11.7T/16 cm冷冻探头1H和X核临床前扫描仪 超高分辨率功能、结构和代谢成像研究中心(MRRC) 动物、固定组织和人体器官。我们对需求的主要理由是，这个新系统将 更换已有20年历史的11.7T泵浦磁铁，其氦气成本极高，接近 失败了。新的11.7T系统将允许我们杰出的用户群，以及整个NIH的调查人员 继续他们资助的关于可靠的最先进系统的研究，并获得数倍的 通过低温线圈技术获得多模式MRI/MRSI的灵敏度，并回答尖端的基本和 翻译神经科学研究问题。该系统将由MRI/MRSI团队管理 拥有卓越技术专长和数十年运营和开发经验的研究人员 用于MRI/MRSI研究的超高频系统。我们已经通过18个NIH研究项目确定了14个主要用户 将与8个次要用户一起从新系统中受益最大。一些人来自同行机构，他们是 由于我们独特的方法开发，他们在耶鲁MRRC执行他们的临床前MRI/MRSI项目。这个 管理计划建立在我们35年的设施管理经验基础上，具有丰富的经验 由校内和校外研究人员组成的运营、指导和咨询委员会。耶鲁大学 大学将提供总额为2,100,000美元的配套资金，用于 系统的成本和完成安装的费用。该系统还将使实习生教育受益于 许多核心MR教师参与指导研究生和博士后研究员，如 以及课堂教学。通过结合具有卓越梯度性能的超高频和用于1H和 X原子核我们预计敏感度将比现有的不受支持的11.7T提高约2.5到4倍 系统。这些改进将使我们的多核和多模式MRI/MRSI能够转化为 转基因小鼠脑和超高分辨率大鼠脑研究。因此，请求的11.7T将满足 迫切需要为耶鲁大学和其他地方的NIH资助的研究人员进行最先进的MRI/MRSI研究。

Transgenic rodents are the most important translational model for studying pathogenesis and treatment of disease. However magnetic resonance imaging (MRI) and spectroscopy (MRS) as well as spectroscopic imaging (MRSI) studies of transgenic mouse and recently transgenic rat have been limited due to not having sufficient spatial resolution to distinguish key anatomic structures such as cortical columns and layers. With development of ultrahigh field (UHF) animal MR systems, using cryogenic technology for sensitivity enhancement, there is unique opportunity to break this sensitivity barrier allowing ultrahigh resolution functional, structural, and metabolic 3D brain imaging in transgenic models, with a direct path to translation to human studies. The primary goal of this proposal is to install and develop capabilities of a state-of-the-art UHF Bruker 11.7T/16cm preclinical scanner with cryoprobes for 1H and X nuclei at Yale's Magnetic Resonance Research Center (MRRC) for ultrahigh resolution functional, structural, and metabolic imaging in small animals, fixed tissues, and human organoids. Our primary Justification of Need is that this new system will replace an unsupported 20-year old 11.7T pumped magnet with extremely high helium costs that is close to failure. The new 11.7T system will allow our outstanding userbase, and investigators throughout the NIH community, to continue their funded research on a reliable state-of-the-art system, and obtain several-fold sensitivity gains for multi-modal MRI/MRSI via cryogenic coil technology and to answer cutting edge basic and translational neuroscience research questions. The system will be managed by a team of MRI/MRSI researchers with outstanding Technical Expertise and decades of track record in operating and developing UHF systems for MRI/MRSI studies. We have identified 14 Major Users with 18 NIH Research Projects that will most benefit from the new system along with 8 Minor Users. Several are from peer institutions who are performing their preclinical MRI/MRSI projects at Yale MRRC due to our unique method developments. The Administration plan builds on our 35-year experience in facility management, with highly experienced operations, steering, and advisory committees with leading intramural and extramural researchers. Yale University will provide a substantial Institutional Commitment totaling $2,100,000 in matching funds towards the system's cost and pay for complete installation. The system will also benefit Trainee Education based on participation of many of the core MR faculty in mentoring of graduate students and post-doctoral fellows, as well as classroom teaching. By combining UHF with superior gradient performance and cryoprobes for 1H and X nuclei we anticipate an approximately 2.5- to 4-fold gain in sensitivity over our existing unsupported 11.7T system. These improvements will allow translation of our multinuclear and multimodal MRI/MRSI to studies of the transgenic mouse brain and ultrahigh resolution rat brain studies. Thus, the requested 11.7T will fulfill urgent needs for state-of-the-art MRI/MRSI research for NIH-funded investigators at Yale, and elsewhere.