Proton Electron Double Resonance Imaging (PEDRI) of Free Radicals

描述（由申请人提供）：本提案旨在开发新型仪器，利用动态核极化（DNP）和质子电子双共振成像（PEDRI）快速测量和成像生物医学应用中的自由基。一种独特的可变场，快速场循环（FC） PEDRI仪器将被建造，能够在0到0.2 t的范围内进行测量。DNP/PEDRI可以提供活体动物自由基的快速高质量测量，这些新的双共振技术克服了EPR成像的一些基本限制，这些限制需要相对较长的图像数据收集时间，由于顺磁标签固有的宽线宽度，提供有限的图像分辨率。并且需要非常大的梯度和独立的解剖配准技术。因此，DNP和PEDRI有很大的潜力来推进这一领域提供：敏感，快速和高质量的测量和成像的顺磁分子在生物医学系统。主要有5个目标：1)开发用于疾病小动物模型中自由基PEDRI优化的磁体、梯度、场控制和系统控制接口；(2)基于核磁共振的自由基EPR光谱检测与成像的变场EPR预激发DNP光谱和PEDRI技术的发展；3)开发现场循环DNP和光谱-空间PEDRI，提高测量灵敏度，减少功率沉积和样品加热问题；4)开发针对体内和离体生物医学应用的DNP和PEDRI优化的创新谐振器和射频设计；5)开发优化软件和算法，实现DNP和PEDRI光谱和图像数据的快速采集和分析。这些目标将共同克服射频功率沉积的现有限制，并导致开发一种独特的可变场快速场循环PEDRI/DNP仪器，能够快速，高质量地测量和成像小动物疾病模型中的自由基。与之前的固定场PEDRI仪器相比，这种新仪器以及在快速场循环、谐振器技术和超快速图像采集方面的相关创新，有可能提供100倍的自由基检测灵敏度，10倍的图像分辨率和10倍以上的图像采集速度，同时将RF功率沉积减少两个数量级以上。

DESCRIPTION (provided by applicant): This proposal is for development of novel instrumentation to enable rapid measurement and imaging of free radicals in biomedical applications using Dynamic Nuclear Polarization (DNP) and Proton Electron Double Resonance Imaging (PEDRI). A unique variable field, rapid field cycling (FC) PEDRI instrument will be built capable of performing measurements from fields of 0 to 0.2 T. DNP/PEDRI can provide rapid high quality measurements of free radicals in living animals and these novel dual resonance techniques overcome a number of the fundamental limitations of EPR imaging that requires relatively long times for image data collection, provides limited image resolution due to the inherently broad linewidths of paramagnetic labels, and needs very large gradients as well as independent techniques for anatomic registration. Therefore, DNP and PEDRI have great potential to advance this field providing: sensitive, rapid and high quality measurements and imaging of paramagnetic molecules in biomedical systems. There are 5 aims: 1) Development of a magnet, gradient, field control, and system control interface optimized for PEDRI of free radicals in small animal models of disease; 2) Development of DNP spectroscopy and PEDRI with variable field EPR preexcitation for NMR based detection and imaging of the EPR spectra of free radicals; 3) Development of Field Cycled DNP and Spectral-Spatial PEDRI to enhance measurement sensitivity and minimize problems with power deposition and sample heating; 4) Development of innovative resonator and RF design optimized for DNP and PEDRI of in vivo and ex vivo biomedical applications; 5) Development of optimized software and algorithms enabling rapid acquisition and analysis of DNP and PEDRI spectral and image data. Together these aims will overcome existing limitations of RF power deposition and result in the development of a unique variable field rapid field cycling PEDRI/DNP instrument capable of rapid, high quality measurement and imaging of free radicals in small animal models of disease. This new instrumentation and related innovations in rapid field cycling, resonator technology and ultra fast image acquisition, have the potential to provide 100-fold enhanced sensitivity in radical detection, with 10-fold higher image resolution and over 10-fold faster image acquisition than prior fixed field PEDRI instrumentation, while reducing RF power deposition by over two orders of magnitude.