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: 8458951
• 负责人: Valery V Khramtsov
• 金额: $ 32.36万
• 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/8458951
• 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）：该项目的总体目标是将质子电子双共振技术（PEDRI）推进到能够对生理关键参数（例如 pH、氧、氧化还原和细胞内谷胱甘肽）进行功能绘图的水平(GSH)，在动物中，也可能在人类中。为了实现这一目标，我们将使用可变射频 (VRF) PEDRI 的新概念与一系列特定的顺磁探头相结合。这将允许在 MRI 内进行功能映射，高质量的空间分辨率和短的时间 采集时间。这项新提案是我们最近的 R21 的逻辑扩展，R21 成功验证了功能性 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 中心提供可能性。考虑到 VRF PEDRI 系统可以通过消除场循环线圈组件及其电源来简化设计，从而完全利用传统 MRI 磁体系统中的间隙，因此该提案具有广阔的前景。具体目标是： (SA1) 使可变射频 PEDRI 能够用于体内功能成像。我们将重点关注 VRF PEDRI 的进一步开发和优化，它是 PEDRI 的仪器创新修改，在探索性 R21 阶段已被发现对于功能应用非常有效。 (SA2) 设计面向 PEDRI 的 pH、氧气、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，包括双功能探针，具有扩展的水溶性和稳定性。探针的合成和优化对于功能性 PEDRI 应用的整体效率至关重要。 (SA3) 使用 VRF PEDRI 实时绘制肿瘤微环境的参数。 VRF PEDRI 进行体内 pH 和氧气绘图的能力将在自发患乳腺癌的 PyMT 转基因小鼠中得到最有效的探针验证。我们计划进行 VRF PEDRI 成像，并随着乳腺肿瘤进展为恶性肿瘤，构建肿瘤 pO2、pH、氧化还原和 GSH 的实时、空间分辨和阶段特异性特征曲线。总之，该项目的成功可能会对体内功能成像在医学中的应用的未来产生重大影响。