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。为了达到这一目标，我们将使用可变场（VF）和可变射频（VRF）质子电子双磁共振成像（PEDRI）的新概念，并结合特定顺磁探头的设计。这将允许在MRI高质量空间分辨率和短采集时间内使用功能绘图（例如氧或pH值绘图）。具体目标是：（SA1）开发用于顺磁探针功能成像的变场PEDRI。该方法将允许使用现有探针进行pH定位，筛选新合成的探针，并优化VRF PEDRI光谱参数以进行功能pH和氧定位。（SA2）开发pedri定向功能探针：硝基自由基和三烷基自由基。将合成具有增强还原稳定性的氮氧化物探针和双功能pH-和氧三芳基甲基探针，并将其用于VF/VRF PEDRI。探针的合成和优化对于功能性PEDRI应用的整体效率至关重要。（SA3）开发用于活体组织功能定位的可变射频PEDRI。VRF PEDRI是对PEDRI方法的一种工具创新修改。与VF PEDRI相比，该方法将使用固定磁场，但EPR射频激励频率略有不同，从而改善磁场均匀性和稳定性，并缩短采集时间。这也将为未来基于传统核磁共振梯度的简化PEDRI系统的发展提供机会。功能性PEDRI对体内pH和氧定位的能力将被证明是FVB/N雌性小鼠PyMT乳腺肿瘤中最有效的探针。在肿瘤微环境中，氧和pH值的变化是肿瘤进展的指示，是预后和治疗的重要因素。综上所述，该项目的成功可能对体内功能成像在医学上的应用产生重大影响。公共卫生相关性：该项目将开发基于特定顺磁探针的MRI的活体组织功能制图的新模式。应用实验将使用新设计的探针来绘制活体小鼠乳腺肿瘤的pH值和氧图谱。所开发的技术可能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.