液体原位脉冲动态核极化增强方法研究

Dynamic nuclear polarization (DNP) is an electron-nuclear double resonance technique, which transfers the higher electron spin polarization to nuclear spins to enhance the nuclear detection sensitivity. This is a superior tool to enhance the biological molecules sensitivity in vivo, particularly for small biological molecule magnetic resonance imaging sensitivity, and it is possible to enhance MRI sensitivity by DNP for molecular imaging. However, a limited sample size and the sharp rising in the temperature of the biological fluid sample caused by microwave heating effect are problems with the existing DNP method. The purpose of this proposal is to develop an efficient method to research DNP-MRI with large sample volume and low heat effects at room temperature in home-built dynamic nuclear polarization-magnetic resonance spectrometer. It includes the following sections: (1) improving the efficiency of polarization signal and reduce microwave heating effect through developing new pulse sequences, exploring DNP enhanced mode; (2) a low electric field DNP-NMR double resonance probe is designed and optimized for large sample size to reduce the heating effect. (3) DNP weighted magnetic resonance imaging and contrast enhancement mechanism. This methodology enhanced sensitivity of NMR in situ at room temperature in liquid DNP can be used for studying the new DNP effect in solutions of macromolecules and can also be applied to the liquid DNP-enhanced NMR image (DNP-MRI).

动态核极化(DNP)是一种电子-核双共振技术，通过将高的电子极化转移到核上以增强核的极化度，从而提高磁共振信号灵敏度。该技术可用于增强体内生物分子信号，尤其是重要生物小分子磁共振信号，使得DNP增强MRI (DNP-MRI)分子影像成为可能。然而，现有DNP方法存在样品大小有限以及微波加热效应引起生物液体样品温度急剧上升等问题。本项目将结合自主研制的脉冲动态核极化增强磁共振装置研究常温下样品容量大、发热效应低的高效DNP检测方法，主要研究内容包括：设计和改进脉冲序列,发展DNP增强方法，提高极化增强效率，降低微波加热效应；研制低电场DNP探头，可适合于大液体样品的同时降低发热效应；研究DNP增强的磁共振成像加权机制与对比度增强方法。这种在常温下原位液体DNP增强核磁共振灵敏度的技术和方法将为研究溶液大分子体系的NMR信号增强机理和液体DNP增强成像(DNP-MRI)提供有效手段。

项目完成了包括1.7GHz大容量电场、磁场分离探头的0.06T 动态核极化（DNP）仪器的研制，可以进行大口径的岩心分析，提出的一种由裂隙腔和细长导线构成的一体化双共振谐振器的设计方案，获得中国和美国发明专利授权，获得了最大180倍的1H信号增强。..制备了一种新型的DNP极化试剂自旋标记的P(NIPAM-NASI)微凝胶，在自研DNP仪器上研究了该凝胶的DNP增强效果，0.35T与0.06T场强下 DNP的1H增强一致，最高可达到133倍，对该微凝胶进行1H MRI测试，得到了增强的MRI图像；以室温液态环境下纳米金刚石为极化剂，在自主研制的0.06T DNP谱仪上，实现了22倍的极化增强，远大于目前文献报道的4倍。针对不同润湿相流体在微米孔径多孔材料中的增强机理、变化规律进行了深入研究，揭示了微米尺度下DNP增强与材料结构、表面特性之间的相关性；开展了微米尺度下Overhauser效应的调控机制的研究，提出了一种利用极化增强剂+弛豫试剂选择性的增强流体相信号进行两相识别的方法。同时，对材料中不同流体相DNP增强的变化进行了测试分析，研究发现其强弱与流体黏度相关，由此提出了一种利用DNP-NMR进行流体相识别与表征的方法，相关研究成果发表在FUEL上（2019(257): 116107）。