Producing Large Quantities of Polarized Xenon with DNP Method

描述（由申请人提供）：先进成像方法的进步为肺部疾病的结构和功能表征提供了新的方法。高分辨率计算机断层扫描（HRCT）显然是目前的领导者，它提供了高空间分辨率、速度，并允许最好的组织密度区分。然而，HRCT的根本缺点是将受试者暴露在电离辐射下，只能提供有关肺结构的信息。传统的MRI提供了一个更安全的平台，但也受到肺实质中水质子的低信噪比的影响，导致图像不佳。然而，最近超极化气体MRI的发展克服了传统MRI的缺点，通过直接成像气道中的气体核（3He或129Xe）。因此，它是最实用的技术，可以超越基于组织密度的测量，实现肺功能的高分辨率成像。尽管前景光明，但需要注意的是，超极化气体MRI领域的进一步发展需要解决该技术的基本挑战：3He气体在全球范围内的供应有限，成本高昂，（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极化129Xe气体的能力有限。该提案的主要目标是开发一个产生大量高极化129Xe气体的新平台。具体来说，我们建议使用动态核极化技术在一天内制造1摩尔高极化气体（在>50%极化水平下约22.4升）。此外，我们计划使其实际交付

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.