600 MHz NMR/MRI Console

 描述（由申请人提供）：心肌代谢和线粒体功能对心力衰竭发病机制和心肌活力的影响在鉴定治疗靶点的努力中变得越来越优先，并且用于评价完整、功能或体内心脏中所有这些参数的有力手段是使用NM光谱学和成像。由于心血管疾病仍然是美国最大的死亡原因，并且越来越多地被认为是美国女性的主要死亡原因，因此，心血管研究中心NMR机构必须保持与600 MHz NMR/MRI系统控制台连接的14.098 T宽孔（89 mm）磁体（Bruker Biospin）的可靠和最先进的能力。该600 MHz系统支持在线评估完整跳动心脏中代谢通量的特定目标，使用该实验室开创的稳定同位素动力学，独特的高分辨率标记心脏MR成像，以透壁检测体内小鼠心脏1 mm厚左心室壁的心脏功能受损早期指标，舒张功能障碍的MRI，心脏病新型转基因模型的体外生物化学表征和多器官MRE的新应用。依赖于该设备的14个现行NIH赠款每年直接费用共计3，680，814美元。主要用户是PI的8个R 01赠款，NIH MERIT奖（R37），先锋奖（DP 1）和计划项目补助金（P01）。美国国立卫生研究院的赠款将该系统的承诺扩展到正在进行的初步工作。这些项目代表了NIH的广泛支持，但有关闭的风险，因为用于这些NIH承诺的现有Bruker DRX 600 MHz控制台已经过时，不再生产电子产品，并且不支持作为现有产品线提供服务。特别关注的是在13年历史的DRX控制台中缺乏信号发生器单元（SGU），其需要第三方频率合成器，该第三方频率合成器也不再被生产用于与DRX控制台对接。严酷的现实是，一个电子故障可能会关闭NIH赞助的项目，MERIT奖和许多R 01类型的赠款。纵向研究已经受到损害，由于不合时宜的系统停机和延迟提供第三方频率合成器。为了避免当前和未来NIH赞助的工作最终关闭，并提高数据质量和当前研究的范围，我们建议为新的AVANCEIII 600 MHz控制台（Bruker Biospin）提供资金。拟议的控制台将提高以下关键需求：1）系统能力; 2）系统可靠性; 3）系统兼容性。与分散的研究重点相反，该提案支持广泛而有凝聚力的研究，这些研究严重依赖于NMR和MRI，这些研究集中在确定疾病的基本机制和开发治疗方法以对抗目标机制的中心长期目标上。研究人员联盟包括校园，区域和国家研究人员和合作，有可能获得资金支持新的NIH资助PI并建立新的强大合作。

 DESCRIPTION (provided by applicant): The influences of both heart muscle metabolism and mitochondrial function on the pathogenesis of heart failure and heart muscle viability are becoming increasingly prioritized in efforts to identify therapeutic targets, and a powerful means for evaluating all of these parameters in the intact, functioning or in vivo heart is the use of NM spectroscopy and imaging. With the fact that cardiovascular disease remains the largest cause of death in the nation and being increasingly understood to be the primary cause of death in women in the USA, it is paramount that Center for Cardiovascular Research NMR Facility maintain reliable and state-of-the- art capabilities for the 14.098 T wide bore (89 mm) magnet (Bruker Biospin) interfaced to a 600 MHz NMR/MRI system console. This 600 MHz system supports specific aims for online evaluations of metabolic flux in intact beating hearts using stable isotope kinetics pioneered in this laboratory, unique high resolution tagged cardiac MR imaging to transmurrally detect early indices of impaired cardiac function across the 1 mm thick left ventricular wall of in vivo mouse hearts, MRI of diastolic dysfunction, in vitro biochemical characterization of novel transgenic models of heart disease and novel applications for multi-organ MRE. The 14 active NIH grants dependent on this equipment total $3,680,814 in annual direct costs. Major users are PI's on 8 R01 grants, an NIH MERIT Award (R37), a Pioneer Award (DP1) and a Program Project Grant (P01). Pending NIH grants extend the commitment of the system to ongoing, preliminary work. These projects, representing extensive NIH support, risk shutdown, because the existing Bruker DRX 600 MHz console for these NIH commitments is obsolete with electronics no longer produced, and is not supported for service as an existing product line. A particular concern is the lack of signal generator units (SGU) in the 13-year old DRX console that requires third party frequency synthesizers that are also no longer produced for interfacing to the DRX console. The stark reality is that one electronics failure holds potentil to shutdown work on NIH sponsored program projects, a MERIT award, and numerous R01 type grants. Longitudinal studies have already been compromised due to untimely system downtime and delays in the availability of third party frequency synthesizers. To avert eventual shutdown of current and future NIH sponsored work and enhance the quality of data and scope of current research, we propose funding for a new AVANCEIII 600 MHz console (Bruker Biospin). The console, as proposed, will enhance critical needs: 1) system capability; 2) system reliability; 3) system compatibility. As opposed to a scattered research focus, this proposal supports a broad yet cohesive, range research heavily dependent on NMR and MRI that converge on the central, long-term objective of identifying fundamental mechanisms of disease and developing therapeutic approaches to counter target mechanisms. The consortium of researchers includes on-campus, regional, and national investigators and collaborations, with potential for funding to support new NIH funded PI's and forge new powerful collaborations.