PARACEST AGENTS: OPTIMIZATION FOR HUMAN MR IMAGING

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。这是一个生物工程研究伙伴关系（BRP）的应用程序，涉及波士顿的科学家（贝斯以色列女执事医疗中心），达拉斯（德克萨斯大学达拉斯分校）和纽约州奥尔巴尼（GE Center Research Center）优化PARACEST试剂的化学、生物分布和毒理学，优化脉冲序列和数据收集，以便在临床扫描仪上使用PARACEST试剂进行成像，并证明其在3 T下的大型动物成像中的功效。原则上，PARACEST试剂可以针对任何数量的生物应用进行定制，因为CEST效应取决于水交换速率，并且可以使用合理的化学原理来修改这些速率。这一特性也使它们成为开发响应式代理的有吸引力的平台。为了实现这些化合物作为体内造影剂的全部潜力，必须系统地解决一些基本的、理论的和实践的问题。这些包括建立在成像实验中测量的效果的大小和水交换寿命之间的关系，结合和散装水之间的化学位移差的大小，饱和RF场的强度，SAR，浓度和局部环境在体内。这项建议将解决所有这些问题。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a bioengineering research partnership (BRP) application involving scientists in Boston (Beth Israel Deaconess Medical Center), Dallas (University of Texas at Dallas) and Albany, NY (GE Center Research Center) to optimize the chemistry, biodistribution, and toxicology of PARACEST agents, optimize pulse sequences and data collection for imaging with PARACEST agents on clinical scanners, and demonstrate their efficacy in large animal imaging at 3T. In principle, PARACEST agents can be tailored to any number of biological application because the CEST effect depends upon water exchange rates and these rates can be modified using rational chemical principles. This feature also makes them an attractive platform for the development of responsive agents. To realize the full potential of these compounds as contrast agents in vivo, a number of basic, theoretical and practical questions must be systematically addressed. These include establishing the relationships among the magnitude of the effect measured in an imaging experiment and the water exchange lifetime, the magnitude of the chemical shift difference between the bound and bulk water, the strength of the saturating RF field, SAR, concentration, and local environment in vivo. This proposal will address all of these issues.