Integration of High Field MRI and EPRI For Functional Imaging

描述（由申请人提供）：包括氧、氧自由基和一氧化氮的顺磁性分子调节细胞功能和损伤，改变关键细胞过程，如呼吸和氧化还原状态，并改变组织灌注、能量状态和活力。考虑到这些相互作用在正常心血管功能和疾病中的关键重要性，非常需要一种方法来将顺磁性分子的体内测量和成像与疾病动物模型中的组织和器官生化和功能参数的成像相结合。EPR成像（EPRI）是一种功能强大的技术，能够进行自由基代谢、氧合和一氧化氮的三维空间体内标测;然而，由于需要补充解剖和功能数据，EPRI的实用性和功能受到很大限制。基于NMR的MRI除了提供解剖配准之外，还可以提供解释EPRI数据所需的关键功能信息，包括组织灌注和活力的成像。集成的EPR/NMR成像技术和仪器具有独特的潜力，使自由基，氧和一氧化氮的体内映射沿着基于NMR的功能和解剖成像。这项技术是非常有前途的，但目前几个基本问题限制了它的发展和生物医学应用。其中包括需要：[a]提供EPR和NMR-MRI系统的无缝集成，以实现这两种成像模式之间的快速转换; [B]构建适合特定生物医学应用的EPR和NMR共振的双模式谐振器; [c]加速两种模式下的图像数据收集过程，促进双模式解剖和功能成像;[d]提高灵敏度并最大限度地减少运动引起的噪声或图像失真; [e]整合EPRI和MRI结果和分析，以执行准确的图像配准、快速计算和功能数据解释。这些关键需求将通过硬件和软件开发的组合来解决，然后进行心血管应用测试，如3个具体目标所述：I.开发和构建EPRI硬件，优化高灵敏度快速扫描图像采集，并将其与高场MRI集成; II.开发/实施集成软件和算法，用于快速EPRI和NMR MRI采集，具有心脏门控功能，可实现解剖结构、灌注、能量状态和活力（MRI）与自由基分布、氧化还原状态和血氧测定（EPRI）的共同映射。将使用NMR图像信息加速和改进EPRI采集，以改进EPR数据收集; III.应用于心脏的双模式功能成像，体内和体外测量组织O2水平、氧化还原状态、与灌注、活力和能量状态（MRI）相关的一氧化氮形成（EPRI）。该计划将实现集成的真实的时间EPRI和高场MRI的巨大协同作用和力量，优化用于自由基、氧化还原状态、O2和一氧化氮的生物医学测量和成像及其在功能和疾病中的作用。

DESCRIPTION (provided by applicant): Paramagnetic molecules including oxygen, oxygen radicals and nitric oxide modulate cellular function and injury, altering critical cellular processs such as respiration and redox state with changes in tissue perfusion, energetic state and viability. In view of the critical importance of these interactions in normal cardiovascular functin and disease, there has been a great need for an approach to combine in vivo measurement and imaging of paramagnetic molecules with imaging of tissue and organ biochemical and functional parameters in animal models of disease. EPR imaging (EPRI) is a powerful technique that enables 3D spatial in vivo mapping of radical metabolism, oxygenation, and nitric oxide; however, the utility and power of EPRI has been greatly limited by the need for complementary anatomic and functional data. NMR based MRI, in addition to providing anatomic registration, also can provide critical functional information that is needed to interpret the EPRI data including, imaging of tissue perfusion and viability. Integrated EPR/NMR imaging technology and instrumentation has the unique potential to enable in vivo mapping of free radicals, oxygen and nitric oxide along with NMR based functional and anatomic imaging. This technology is very promising but several fundamental problems presently limit its development and biomedical application. These include the need to: [a] provide seamless integration of the EPR and NMR-MRI systems to enable rapid transition between these two imaging modalities; [b] build dual mode resonators optimized for both EPR and NMR resonances suited for specific biomedical applications; [c] accelerate the process of image data collection in both modes facilitating dual mode anatomic and functional imaging; [d] increase sensitivity and minimize motion-induced noise or image distortion; [e] integrate the EPRI and MRI results and analysis in order to perform accurate image co-registration, fast computation and interpretation of functional data. These critical needs will be addressed with a combination of hardware and software development followed by testing in cardiovascular applications as described in 3 specific aims: I. Development and construction of EPRI hardware optimized for high sensitivity fast scan image acquisition and integration of it with high field MRI; II. Development / implementation of integrated software and algorithms for fast EPRI and NMR MRI acquisition with cardiac gating enabling co-mapping of anatomic structure, perfusion, energetic state and viability (MRI) with free radical distribution, redox state and oximetry (EPRI). EPRI acquisition will be accelerated and refined using NMR image information to refine EPR data collection; III. Application for dual mode functional imaging of the heart with both in vivo and ex vivo measurement of tissue O2 levels, redox status, nitric oxide formation (EPRI) in relation to perfusion, viability, and energeic state (MRI). This program will realize the great synergy and power of integrated real time EPRI and high field MRI optimized for biomedical measurement and imaging of free radicals, redox state, O2, and nitric oxide and their role in function and disease.