PARACEST AGENTS: OPTIMIZATION FOR HUMAN MR IMAGING

PARACEST Agents：人类 MR 成像的优化

• 批准号: 7724130
• 负责人: ROBERT E LENKINSKI
• 金额: $ 1.05万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7724130
• 关键词: Address; Area; Binding; Chemicals; Chemistry; Class; Computer Retrieval of Information on Scientific Projects Database; Contrast Media; Detection; Development; Environment; Frequencies; Funding; Gadolinium; Goals; Grant; Human; Image; In Vitro; Institution; Lanthanoid Series Elements; Lead; Magnetic Resonance Imaging; Measures; Numbers; Perfusion; Physiologic pulse; Pulse taking; Rate; Research; Research Personnel; Resources; Signal Transduction; Source; Spin Labels; United States National Institutes of Health; Validation; Water; human study; in vivo; irradiation; research study; simulation; theories

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. Paramagnetic chemical exchange saturation transfer (PARACEST) agents offer a potential new paradigm in MR imaging. An advantage to this class of agents is the ability to switch each agent on or off through selective RF irradiation applied at the frequency of either its bound water resonance or an exchanging NH group. This feature means that multiple, targeted PARACEST agents can be injected together and their effects imaged either sequentially or simultaneously. In their ""off"" state, i.e. when not specifically irradiated, PARACEST agents will not interfere with conventional MR imaging sequences, with or without gadolinium. In principle, PARACEST agents can be tailored to each application because their effects depend on their 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 and bifunctional agents. The goal of this BRP is to realize the full potential of these compounds as contrast agents in vivo, by systematically addressing a number of basic, theoretical and practical questions. 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 partnership is made up of two academic institutions and an industrial collaborator. The three main overlapping and interactive areas of focus are: lanthanide chemistry, which will be carried out at UT Dallas (UTD); Pulse sequence implementation, theory, simulations and in vitro validation which will be carried out primarily at the General Electric Global Research Center (GEGRC) and in vivo validation carried out primarily at the BIDMC. Dean Sherry (Project Leader, UTD) is an internationally recognized expert in the synthesis and characterization of lanthanide chelates. Donald Woessner (Lead Investigator, UTD), an internationally recognized expert in basic NMR exchange theory.Thomas Dixon and lleana Hancu (Project Leaders, GEGRC) are both experts in NMR and MR imaging. Robert Lenkinski (PI, BIDMC) is an NMR spectroscopist with expertise both in lanthanide agents and MR imaging. David Alsop (Lead Investigator, BIDMC) has a long track record in optimizing Arterial Spin Labeling perfusion studies, where the detection of small signal intensity changes in the presence of RF irradiation is necessary. Over the past several years, this team has been collaborating on the theoretical and practical aspects of the PARACEST effect. The successful completion of this project will result in a set of agents and MR acquisition strategies for use in human studies.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 顺磁化学交换饱和转移（Paracest）代理在MR成像中提供了潜在的新范式。这类代理的优势是能够通过以其结合的水共振或交换NH组施加的选择性RF辐射开关或关闭每个代理的能力。此功能意味着可以将多种靶向的极偏最大的药物注入在一起，并同时或同时成像。在其“ OFF”状态中，即当不是特别受辐照的情况下，最有偏的药物不会干扰有或没有gadolinium的常规MR成像序列。原则上，可以为每个应用程序量身定制最高的代理，因为它们的影响取决于其水汇率，并且可以使用合理的化学原理对这些速率进行修改。此功能还使它们成为开发响应式代理和双功能代理的有吸引力的平台。该BRP的目的是通过系统地解决许多基本的，理论和实用的问题来实现这些化合物作为体内对比剂的全部潜力。其中包括建立在成像实验和水交换寿命中测得的效果的关系，结合水和散装水之间的化学位移差异的大小，饱和的RF场的强度，SAR，SAR，浓度和Vivo的局部环境。该合作伙伴关系由两个学术机构和一个工业合作者组成。重点的三个主要重叠和交互式领域是：灯笼化学，将在UT Dallas（UTD）进行；脉冲序列实施，理论，模拟和体外验证将主要在通用电气全球研究中心（GEGRC）和体内验证中进行，主要是在BIDMC进行的。 Dean Sherry（UTD项目负责人）是国际公认的灯笼螯合物合成和特征的专家。唐纳德·沃斯纳（Donald Woessner）（UTD首席研究员）是基本NMR交换理论的国际认可的专家。ThomasDixon和Lleana Hancu（GEGRC项目负责人）都是NMR和MR Imaging的专家。罗伯特·兰金斯基（Robert Lenkinski）（PI，BIDMC）是一位NMR光谱学家，在灯笼代理和MR成像中都具有专业知识。 David ALSOP（BIDMC的主要研究员）在优化动脉自旋标记灌注研究方面具有较长的记录，其中需要在RF辐照的存在下检测小信号强度变化。在过去的几年中，该团队一直在最偏见的效果的理论和实践方面进行合作。该项目的成功完成将导致一系列代理商和MR获取策略用于人类研究。