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: 8305365
• 负责人: Valery V Khramtsov
• 金额: $ 34.31万
• 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/8305365
• 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

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. PUBLIC HEALTH RELEVANCE: This project will advance the proton-electron double-resonance imaging 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. The functional imaging technique will be applied in PyMT transgenic mice that spontaneously-develop breast cancer. This will allow for construction of real-time, spatially-resolved and stage-specific signature profiles of tumor pO2, pH, redox, and GSH as the mammary tumors progress to malignancy. This novel technique may have a significant impact on future applications relating to biomedical imaging.

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. PUBLIC HEALTH RELEVANCE: This project will advance the proton-electron double-resonance imaging 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. The functional imaging technique will be applied in PyMT transgenic mice that spontaneously-develop breast cancer. This will allow for construction of real-time, spatially-resolved and stage-specific signature profiles of tumor pO2, pH, redox, and GSH as the mammary tumors progress to malignancy. This novel technique may have a significant impact on future applications relating to biomedical imaging.