Functional Proton Electron Double Resonance Imaging

描述(由申请人提供)：该项目的总体目标是开发活体组织功能成像的新模式。为了实现这一目标，我们将使用变场(VF)和可变射频(VRF)质子电子双共振成像(Pedri)的新概念，并结合特定顺磁探针的设计。这将允许在MRI内使用功能映射(例如，氧气或pH映射)，高质量的空间分辨率和较短的采集时间。具体目标是：(SA1)开发用于顺磁探头功能成像的变场Pedri。该方法将允许使用可用的探针绘制pH图，筛选新合成的探针，并优化VRF Pedri光谱参数以进行功能性pH和氧绘制。(SA2)开发以PEDRI为导向的功能探针：氮氧基和三叔丁基。将合成具有更高还原稳定性的氮氧化物探针，以及pH-和氧-三芳基甲基双功能探针，并用于VF/VRF Pedri。探针的合成和优化对于功能性PEDRI应用的整体效率是绝对关键的。(SA3)开发用于活组织功能测绘的可变射频Pedri。VRF Pedri是对Pedri方法的工具创新修改。与VF Pedri相比，该方法将使用稳定磁场，但EPR射频激励频率略有不同，从而提高了磁场的均匀性和稳定性，并缩短了捕获时间。这也将为基于常规核磁共振梯度的简化PEDRI系统的未来开发提供机会。功能性Pedri对体内pH和氧气定位的能力将被证明是在FVB/N雌性小鼠的PYMT乳腺肿瘤中最有效的探针。在肿瘤微环境中，氧气和pH的变化都预示着肿瘤的进展，是影响预后和治疗的重要因素。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。公共卫生相关性：该项目将开发基于特定顺磁探针的磁共振成像的活组织功能图谱的新模式。应用实验将使用新设计的探针对活体小鼠的乳腺肿瘤进行pH和氧气测绘。所开发的技术可能会对未来医学成像的应用产生重大影响。

DESCRIPTION (provided by applicant): The overall goal of this project is to develop new modalities of functional imaging in living tissues. To reach this goal we will use a new concept of Variable Field (VF) and Variable Radio Frequency (VRF) proton electron double resonance imaging (PEDRI) in combination with design of specific paramagnetic probes. This will allow for functional mapping using (e.g. oxygen or pH mapping) within MRI high quality spatial resolution and short acquisition time. The specific aims are: (SA1) To develop Variable Field PEDRI for functional imaging of paramagnetic probes. The approach will allow for pH mapping using available probes, screening newly synthesized probes, and optimization of VRF PEDRI spectroscopic parameters for functional pH and oxygen mapping. (SA2) To develop PEDRI-oriented functional probes: nitroxyl and trityl radicals. Nitroxide probes with enhanced stability towards reduction, and dual function pH- and oxygen triarylmethyl probes will be synthesized and used for VF/VRF PEDRI. Synthesis an optimization of the probes is absolutely crucial for the overall efficiency of functional PEDRI applications. (SA3) To develop Variable Radio Frequency PEDRI for functional mapping of living tissues. VRF PEDRI is an instrumentally innovative modification of PEDRI approach. Compared with VF PEDRI this approach will use stationary magnetic field but slightly different EPR RF excitation frequencies resulting improved magnetic field homogeneity and stability, and decreased acquisition time. It will also provide opportunity for future development of a simplified PEDRI system based on conventional NMR gradients. The capacity of the functional PEDRI for in vivo pH and oxygen mapping will be demonstrated for the most effective probes in PyMT mammary tumors of FVB/N female mice. In a tumor microenvironment, both oxygen and pH changes are indicative of tumor progression being important factors for prognosis and treatment. 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 develop new modalities of functional mapping of living tissues based on MRI of specific paramagnetic probes. Application experiments will use newly designed probes for pH- and oxygen mapping of mammary tumors in living mice. The developed technique may have a significant impact on the future applications to medical imaging.