Functional proton-electron double-resonance imaging: development and application

功能性质子电子双共振成像：开发与应用

• 批准号: 8645629
• 负责人: Valery V Khramtsov
• 金额: $ 33.28万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-15 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8645629
• 关键词: Accounting; Acidosis; Animals; Biological; Clinical; Computer software; Data; Data Collection; Development; Electrons; Frequencies; Functional Imaging; Future; Glutathione; Glycolysis; Goals; Grant; Human; Hypoxia; Image; Imaging Techniques; Life; Magnetic Resonance Imaging; Malignant Neoplasms; Mammary Neoplasms; Maps; Measures; Medicine; Modification; Mus; Oryctolagus cuniculus; Oxidation-Reduction; Oxygen; Phase; Physiologic pulse; Physiological; Power Sources; Protons; Radio; Relaxation; Research; Resolution; Sampling; Signal Transduction; Solubility; Source; Specificity; Staging; Structure; System; Techniques; Time; Tissues; Toxicokinetics; Transgenic Mice; Tumor Tissue; United States National Institutes of Health; Work; aqueous; base; bioimaging; clinical application; design; dosage; expectation; experience; in vivo; innovation; instrumentation; irradiation; magnetic field; malignant breast neoplasm; nitroxyl; novel; ratiometric; success; tumor; tumor microenvironment

DESCRIPTION (provided by applicant): The overall goal of this project is to advance the proton-electron double-resonance technique, PEDRI, to a level allowing for functional mapping of physiologically-critical parameters, such as pH, oxygen, redox and intracellular glutathione (GSH), in animals and, potentially, in humans. To reach this goal we will use a new concept of Variable Radio Frequency (VRF) PEDRI in combination with an array of specific paramagnetic probes. This will allow for functional mapping within MRI high quality spatial resolution and short acquisition time. This new proposal is a logical extension of our recent R21 which was successful in validating the concept of functional PEDRI. The success of this proposal will open possibilities for bringing this new PEDRI technique into the leading research and clinical MRI centers. This proposal has promising potential taking into account that VRF PEDRI system allows for the simplified design by elimination of the field cycling coil assembly and its power supplies which will result in a complete utilization of the gap in the magnet system of conventional MRIs. The specific aims are: (SA1) To enable Variable Radio Frequency PEDRI for in vivo functional imaging. We will focus on the further development and optimization of VRF PEDRI, which is an instrumentally-innovative modification of PEDRI and has been found to be highly efficient for functional applications during the exploratory R21 phase. (SA2) To design PEDRI-oriented pH, oxygen, redox and GSH sensitive paramagnetic probes. The probes with functionally-dependent ratiometric spectral parameters, including dual function probes, with extended aqueous solubility and stability will be synthesized. Synthesis and optimization of the probes is absolutely essential for the overall efficiency of functional PEDRI applications. (SA3) To map in real-time the parameters of a tumor microenvironment using VRF PEDRI. The capacity of the VRF PEDRI for in vivo pH and oxygen mapping will be demonstrated for the most effective probes in PyMT transgenic mice that spontaneously-develop breast cancer. We plan to perform VRF PEDRI imaging and construct real-time, spatially-resolved and stage-specific signature profiles of tumor pO2, pH, redox, and GSH as the mammary tumors progress to malignancy. In summary, the success of this project may have a significant impact on the future of in vivo functional imaging applications to medicine.

描述（由申请人提供）：本项目的总体目标是将质子-电子双共振技术（PEDRI）推进到允许在动物和潜在的人类中对生理关键参数（如pH值、氧、氧化还原和细胞内谷胱甘肽（GSH））进行功能映射的水平。为了实现这一目标，我们将使用可变射频（VRF）PEDRI的一个新的概念，结合特定的顺磁探针阵列。这将允许MRI内的功能标测高质量空间分辨率和短 收购时间。这个新的建议是我们最近的R21的逻辑扩展，它成功地验证了功能PEDRI的概念。该提案的成功将为将这种新的PEDRI技术引入领先的研究和临床MRI中心开辟可能性。考虑到VRF PEDRI系统允许通过消除场循环线圈组件及其电源来简化设计，这将导致完全利用常规MRI的磁体系统中的差距，因此该提议具有很好的潜力。具体目标是：（SA 1）使可变射频PEDRI能够用于体内功能成像。我们将专注于VRF PEDRI的进一步开发和优化，这是PEDRI的工具创新修改，并已被发现在探索性R21阶段的功能应用非常有效。(SA2)设计PEDRI导向的pH、氧、氧化还原和GSH敏感的顺磁探针。将合成具有功能依赖性比率光谱参数的探针，包括具有扩展的水溶性和稳定性的双功能探针。探针的合成和优化对于功能性PEDRI应用的整体效率是绝对必要的。(SA3)使用VRF PEDRI实时绘制肿瘤微环境的参数。VRF PEDRI用于体内pH和氧映射的能力将在自发发展乳腺癌的PyMT转基因小鼠中被证明是最有效的探针。我们计划进行VRF PEDRI成像，并构建实时，空间分辨和阶段特异性的肿瘤pO 2，pH值，氧化还原和GSH的签名配置文件作为乳腺肿瘤进展到恶性肿瘤。总之，该项目的成功可能会对体内功能成像在医学上的应用产生重大影响。