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

转基因啮齿动物是研究该病发病机制和治疗的最重要的转化模型 疾病然而，磁共振成像（MRI）和波谱（MRS）以及光谱成像（MRS）可以被用于测量磁共振成像（MRI）和波谱（MRS）。 转基因小鼠和最近的转基因大鼠的成像（MRSI）研究由于没有 足够的空间分辨率，以区分关键的解剖结构，如皮质柱和层。与 开发超高频（UHF）动物MR系统，采用低温技术提高灵敏度 增强，有独特的机会，打破这一敏感性障碍，使分辨率 转基因模型中的功能，结构和代谢3D脑成像，直接翻译为 人类研究该提案的主要目标是安装和开发最先进的 UHF Bruker 11.7T/16 cm临床前扫描仪，配备冷冻探针，用于耶鲁磁共振的1H和X核 研究中心（MRRC），用于小样本的高分辨率功能，结构和代谢成像 动物、固定组织和人类类器官。我们的主要理由是，这个新系统将 替换一个使用了20年的11.7T泵吸磁铁，其氦气成本极高， 失败新的11.7T系统将使我们优秀的用户群和整个NIH的研究人员 社区，继续他们资助的研究一个可靠的国家的最先进的系统，并获得几倍 通过低温线圈技术提高多模态MRI/MRSI的灵敏度， 转化神经科学研究问题。该系统将由MRI/MRSI团队管理 拥有杰出的技术专长和数十年的运营和开发记录的研究人员 用于MRI/MRSI研究的UHF系统。我们已经确定了14个主要用户与18个NIH研究项目， 沿着8名未成年用户将从新系统中受益最多。有几个来自同行机构， 由于我们独特的方法开发，他们在耶鲁MRRC进行临床前MRI/MRSI项目。的 行政计划建立在我们35年的设施管理经验之上， 业务，指导和咨询委员会与领先的校内和校外研究人员。耶鲁 大学将提供一个巨大的机构承诺，总额为210万美元的配套资金， 系统的成本和支付完整的安装。该系统还将有利于培训人员教育， 许多核心MR教师参与指导研究生和博士后研究员， 以及课堂教学。通过将超高频与上级梯度性能和冷冻探针相结合， X核，我们预计灵敏度将比现有的不支持的11.7T提高约2.5至4倍 系统这些改进将使我们的多核和多模态MRI/MRSI的翻译研究， 转基因小鼠脑和转基因大鼠脑研究。因此，要求的11.7T将满足 耶鲁大学和其他地方的NIH资助的研究人员迫切需要最先进的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.