Producing Large Quantities of Polarized Xenon with DNP Method

描述（由申请人提供）：先进的成像方法使肺部疾病的结构和功能表征的新方法成为可能。 高分辨率计算机断层扫描（HRCT）显然是目前的领导者，通过提供高空间分辨率，速度，并允许组织密度的最佳区分，然而，HRCT具有将受试者暴露于电离辐射并且仅提供有关肺结构的信息的根本缺点。 常规MRI提供了更安全的平台，但也遭受肺实质中的水质子的低信噪比，导致劣质图像。 然而，超极化气体MRI的最新发展已经通过直接对气道中的气体（3 He或129 He）的核进行成像而克服了常规MRI的缺点。因此，它是超越基于组织密度的测量向肺功能的高分辨率成像发展的最实用的技术。尽管如此，重要的是要注意到，超极化气体MRI领域的进一步进展需要解决该技术的基本挑战：3 He气体的全球供应有限和成本高昂，以及（目前）在没有过于复杂和昂贵的设备的情况下产生足够数量的高度极化129 He气体的能力有限。 该计划的主要目标是开发一个新的平台，用于产生大量高度极化的129氪气体。 具体来说，我们建议使用动态核极化技术在一天内制造一摩尔高度极化的气体（在>50%极化水平下约22.4升）。此外，我们计划使其切实可行， 这种气体被输送到临床试验点的区域网络，同时保持高水平的极化，以便能够进行大规模的人类肺部研究。我们计划通过以下具体目标来实现我们的目标：1）在低温下实现大固体样品中的高129 Ω极化：使用我们开发的129 NMR诊断方法，可以测量DNP过程中的原位温度和弛豫速率，将设计一个优化的系统，用于增加氙/自由基/溶剂混合物的表面积/体积比，以及超流氦浴，以便在几个小时内在冷冻状态下储存大量氙。2）开发在冷冻氙升温至室温和从液体玻璃化剂中相分离的过程中保持偏振的方法：利用已知的129 Ω弛豫速率与温度、磁场和氙同位素组成的关系，将开发在DNP磁体的边缘场中的快速和有效的解冻和相分离程序。3）开发在几百英里的区域距离上输送极化固体氙的方法：将对安装在永久便携式1 T Hallbach磁体中的低温阱进行测试，并将其用于维持浸没固体氙的低温，并在4-5小时的旅行期间保持其极化的显著部分~ 4）开发用于大型动物129氚成像的新技术：我们将展示在正常猪和灌注缺陷猪中进行部分通气/PAO 2成像的可行性，特别关注氚的不同物理特性对成像技术的影响。

DESCRIPTION (provided by applicant): Advances in sophisticated imaging methods have enabled new approaches for structural and functional characterization of pulmonary disorders. High Resolution Computed Tomography (HRCT) is clearly the current leader, by providing high spatial resolution, speed, and allowing the best distinction of tissue density However, HRCT has the fundamental drawback of exposing the subject to ionizing radiation and only providing information about lung structure. Conventional MRI provides a safer platform but also suffers from the low signal-to-noise ratio of water protons in the lung parenchyma resulting in inferior images. Recent developments in hyperpolarized gas MRI however have overcome the shortcomings of conventional MRI by directly imaging the nuclei of a gas (3He or 129Xe) in the airways. It is thus the most practical technique for moving beyond measurements based on tissue-density toward high-resolution imaging of lung function. Despite this promise, it is important to note that further progress in the field of hyperpolarizd gas MRI requires resolution of the fundamental challenges of the technology: the limited worldwide supply and significant expense of 3He gas, and the (currently) limited ability to generate sufficient quantities of highly polarized 129Xe gas without prohibitively complex and expensive devices. The main goal of this proposal is to develop a new platform for generating large quantities of highly polarized 129Xe gas. Specifically, we propose to use Dynamic Nuclear Polarization technique to make one mole of highly polarized gas in one day (~22.4 liters at >50% polarization level). Furthermore, we plan to make it practical to deliver this gas to a regional network of clinical test sites while retaining high levels of polarization n order to enable large- scale human lung studies. We plan to accomplish our objective through the following specific aims: 1) Achieve high 129Xe polarization in a large solid sample at the cryogenic temperature: Using our developed 129Xe NMR diagnostic methods that can measure in situ temperature and relaxation rates during DNP, an optimized system for increasing the surface area/volume ratio of xenon/radical/solvent mixture and the superfluid helium bath will be engineered to polarize large volumes of xenon in a few hours in the frozen state~ 2) Develop methods for polarization retention during the warm-up of frozen xenon to room temperature and phase separation from the liquid glassing agent: Using the known dependence of 129Xe relaxation rates on temperature, magnetic field, and xenon isotopic composition, a rapid and efficient thawing and phase-separation procedure in the fringe-field of the DNP magnet will be developed~ 3) Develop methods for transportation of polarized solid xenon over regional distances of several hundred miles: A cryogenic trap mounted in a permanent portable 1-T Hallbach magnet will be tested and used to sustain the low temperature of the immersed solid xenon and preserve a significant fraction of its polarization over the duration of a 4-5 hour trip~ 4) Develop new techniques for 129Xe imaging in large animals: We will show the feasibility of fractional ventilation / PAO2 imaging in normal pigs and those with perfusion defects, with a particular focus on the effect of Xe's differing physical properties on the imaging techniques.