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

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提高到一个水平，从而能够在动物中以及可能在人类中对生理关键参数，如pH、氧、氧化还原和细胞内谷胱甘肽(GSH)进行功能图谱绘制。为了实现这一目标，我们将使用可变射频(VRF)Pedri的新概念，并结合一系列特定的顺磁探头。这将允许在MRI内进行高质量的空间分辨率和短时间的功能映射 获取时间。这一新提议是我们最近成功验证功能性Pedri概念的R21的合乎逻辑的扩展。这项提议的成功将为将这种新的Pedri技术引入领先的研究和临床核磁共振中心提供可能性。考虑到VRF Pedri系统可以通过取消磁场循环线圈组件及其电源来简化设计，这一建议具有很大的潜力，这将导致完全利用传统磁共振成像磁体系统中的缺口。具体目标是：(SA1)使可变射频Pedri能够用于活体功能成像。我们将专注于VRF Pedri的进一步开发和优化，VRF Pedri是对Pedri的仪器创新修改，已被发现在探索性R21阶段对功能应用非常高效。(SA2)设计Pedri取向的pH、氧、氧化还原和GSH敏感的顺磁探针。将合成具有比光谱参数依赖功能的探针，包括具有扩展的水溶解度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参数图。VRF Pedri对体内pH和氧气定位的能力将被证明是在自发发展乳腺癌的PYMT转基因小鼠中最有效的探针。我们计划进行VRF Pedri成像，并构建实时的、空间分辨率的和特定阶段的肿瘤PO2、pH、氧化还原和GSH的特征曲线，随着乳腺肿瘤的恶性进展。综上所述，该项目的成功可能会对活体功能成像在医学上的未来应用产生重大影响。

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.