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和力技术（PEDRI）提高到一个水平，以允许对生理批判性参数的功能映射，例如pH，氧气，氧气，氧化还原和细胞内glut省（氧气），在动物和潜在的人类中。为了实现此目标，我们将使用新的可变射频（VRF）PEDRI概念，并结合一系列特定的顺磁探针。这将允许在MRI高质量空间分辨率和短暂的MRI映射 获取时间。这项新提案是我们最近的R21的逻辑扩展，该扩展成功地验证了功能性PEDRI的概念。该提案的成功将为将这种新的PEDRI技术带入领先的研究和临床MRI中心开放。该提案具有有希望的潜力，即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，这将导致在常规MRIS的磁铁系统中完全利用GAP。具体目的是：（SA1）启用可变射频PEDRI进行体内功能成像。我们将重点关注VRF PEDRI的进一步开发和优化，VRF PEDRI是对PEDRI的工具创新的修改，并且在探索性R21阶段对功能应用非常有效。 （SA2）设计面向PEDRI的pH，氧，氧化还原和GSH敏感的顺磁性探针。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的探针将合成。探针的合成和优化对于功能性PEDRI应用的总体效率绝对必不可少。 （SA3）使用VRF Pedri实时绘制肿瘤微环境的参数。 VRF PEDRI用于体内pH和氧映射的能力将用于自发开发乳腺癌的PYMT转基因小鼠中最有效的探针。我们计划执行VRF PEDRI成像，并在乳腺肿瘤发展为恶性肿瘤时实时，空间分辨和特定阶段的特异性特征特异性特异性特征。总而言之，该项目的成功可能会对医学中体内功能成像应用的未来产生重大影响。