IMQC PULSE SEQUENCE DESIGN FOR USE ON GE SCANNERS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 使用In Vivo Microcope的7T系统开发和测试用于GE扫描仪的iMQC脉冲序列。 这项研究解决了磁共振成像和磁共振波谱(MRS)在体内的基本局限性，增强了它们的实用性，并使新的临床和临床前应用成为可能。MRI和MRS已经成为非常强大的临床手段，其应用也在不断发展。然而，敏感性相对较低，因此在大多数MRI研究中，信号主要来自水，而对比主要来自参数，这些参数通常只与间接的临床相关性或与代谢和细胞生化相关。大多数造影剂的特异性有限，通常需要高浓度才能影响信号。其他分子(MRS)的局域检测受到低浓度、与强水峰的竞争以及(在许多器官中)局部敏感性变化的阻碍，这些变化扩大了共振，从而降低了选择性。 这里提出的研究使用分子间多量子相干(IMQCs)来解决这些基本限制，既包括它们本身，也包括使用长寿的超极化试剂。IMQC对应于溶液中分离的分子同时发生自旋翻转(分离通常为数百微米)。在之前的资助期间，我们开发了显著增强iMQC信号的方法，如iMQC具有明显优势的温度成像应用，放大小肺转移瘤信号的新型造影剂，以及显著延长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特定目标，重点放在有针对性的临床应用和本地化光谱上。这些应用的共同主题是高精度光谱学，通过适当的iMQC序列的内在能力来补偿敏感度变化和不均匀展宽。这种补偿可以在不丢弃化学位移差异的情况下实现，并且分子间的相干可以连接不是紧邻的分子。在异质性很强的器官或组织中(如乳房)，线条宽度的减少是显著的。这些特殊的目的是利用这些特性来使两个有临床前景的研究方向(热疗中的绝对温度成像和棕色脂肪组织检测)成为可能，改善脂肪组织中的质子磁共振波谱，并通过检测水-碳iMQCs的尖锐线条来增强碳超极化试剂的效用。这项工作的范围从体模研究到我们参与正在进行的人类临床试验，并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.