IMQC PULSE SEQUENCE DESIGN FOR USE ON GE SCANNERS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 使用Center for In Vivo Microscopy的7 T系统开发和测试iMQC脉冲序列，以便在GE扫描仪上使用。 该研究解决了MRI和MR波谱（MRS）在体内的基本局限性，增强了它们的实用性，并实现了新的临床和临床前应用。MRI和MRS已经成为非常强大的临床模式，并且应用继续发展。然而，灵敏度相对较低，因此在大多数MRI研究中，信号主要来自水，对比度主要来自参数，这些参数通常仅具有间接的临床相关性或与代谢和细胞生物化学相关。大多数造影剂具有有限的特异性，并且通常需要以高浓度存在以影响信号。其他分子（MRS）的局部检测受到低浓度、与强水峰竞争以及（在许多器官中）局部磁化率变化的阻碍，这些变化会扩大共振，从而降低选择性。 这里提出的研究使用分子间多量子相干（iMQCs）解决了这些基本限制，无论是通过自身还是使用长寿命的超极化试剂。iMQCs对应于溶液中分离分子的同时自旋翻转（分离通常为数百微米）。在上一个资助期，我们开发了显着增强iMQC信号的方法，例如iMQC具有明显优势的温度成像应用，放大小肺转移信号的新型造影剂，以及显着增加特定超极化试剂寿命的方法。自2008年10月以来，这项工作包括两篇发表的科学论文和一篇提交的PNAS论文。 此次更新包括利用这些发展的具体目标，重点是有针对性的临床应用和局部光谱学。这些应用的共同主题是高精度光谱，通过适当的iMQC序列的内在能力来补偿磁化率变化和不均匀加宽。这种补偿可以在不丢弃化学位移差异的情况下实现，并且分子间的内聚力可以连接不紧邻的分子。 在具有实质异质性的器官或组织（例如乳房）中，线宽减小是显著的。具体目标利用这些特性，使两个临床上有前途的研究方向（绝对温度成像在热疗和棕色脂肪组织检测），以改善质子MRS在脂肪组织，并提高碳超极化试剂的效用，通过检测从水碳iMQCs的尖锐线。这项工作的范围从体模研究到我们参与正在进行的人体临床试验，包括创新的脉冲序列开发以及现有序列的应用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Use the Center for In Vivo Microscopy's 7T system to develop and test iMQC pulse sequences for use on a GE scanner. The research addresses fundamental limitations of MRI and MR spectroscopy (MRS) in vivo, enhancing their utility and enabling new clinical and preclinical applications. MRI and MRS have become very powerful clinical modalities, and applications continue to evolve. However, sensitivity is relatively low, so in most MRI studies, the signal arises mostly from water, and contrast arises primarily from parameters, which often only have indirect clinical relevance or correlation with metabolism and cell biochemistry. Most contrast agents have limited specificity, and usually need to be present in high concentration to affect the signal. Localized detection of other molecules (MRS) is hampered by low concentrations, by competition with the strong water peak, and (in many organs) by local susceptibility variations that broaden resonances and thus reduce selectivity. The research proposed here addresses these fundamental limitations using intermolecular multiple- quantum coherences (iMQCs), both by themselves and with long-lived hyperpolarized reagents. iMQCs correspond to simultaneous spin flips on separated molecules in solution (the separation is typically hundreds of microns). In the previous grant period, we developed methods that significantly strengthen iMQC signals, applications such as temperature imaging where iMQCs have clear advantages, novel contrast agents that amplify the signal from small lung metastases, and approaches that dramatically increase the lifetimes of specific hyperpolarized reagents. Just since October 2008, this work includes two published Science papers and a submitted PNAS paper. This renewal includes specific aims, which exploit these developments, with a focus on targeted clinical applications and localized spectroscopy. The common theme of these applications is high precision spectroscopy, enabled by the intrinsic ability of appropriate iMQC sequences to compensate for susceptibility variations and inhomogeneous broadening. This compensation can be achieved without throwing away chemical shift differences, and the intermolecular coherences can connect molecules which are not in immediate proximity. In organs or tissues with substantial heterogeneity (such as the breast) the line width reductions are dramatic. The specific aims exploit these characteristics to enable two clinically promising research directions (absolute temperature imaging in hyperthermic therapy and brown adipose tissue detection), to improve proton MRS in fatty tissue, and to enhance the utility of carbon hyperpolarized reagents by detecting sharp lines from water-carbon iMQCs. This work ranges from phantom studies to our participation in an ongoing human clinical trial, and includes innovative pulse sequence development as well as applications of existing sequences.