Enhanced Optical Module to Enable Polarized 129Xe MRI Use in Clinical Trials

描述（由申请人提供）：目前有50多种新药处于II-III期开发阶段，用于治疗COPD -一种影响1300万美国人的疾病，每年花费490亿美元，造成12万人死亡。然而，在评估这些慢性疾病的治疗方面的一个主要限制是缺乏足够敏感和非侵入性的方法，使药物开发人员能够在几天而不是几个月的时间尺度上观察疗效。如果没有这些方法，昂贵的药物开发计划就会失败，有前途的新药也永远不会进入试验阶段。一个新兴的解决方案是超极化129 MRI，这是一个非常强大的局部肺功能和治疗反应的标志物。然而，其在主要肺中心的可用性目前是有限的。我们的长期目标是建立一个能够广泛部署非侵入性、高分辨率超极化129 μ M MRI作为生物标志物的业务，以帮助加速评估有前途的呼吸系统疾病治疗方法。本申请的目的是 改进尺寸、转换效率，并因此改进129 nm偏振器内的光学单元的经济性。关键的需求是，今天的超极化技术在将激光功率转换为自旋极化129 π ι方面相对低效。超过80%的可用激光功率没有有效地转换成自旋极化。增加额外的激光功率和光学单元体积以克服转换效率低下导致必须安装在专用房间中的大型昂贵单元，该专用房间具有压缩空气源、外部气瓶和紧邻MRI扫描仪的三相电源。该项目的基本原理是，通过使用一种新的光学单元几何形状， 129 μ m，在一个小型，紧凑，经济的系统，采用适度的激光功率，并要求没有什么不寻常的设施。通过解决这一关键瓶颈，我们消除了临床试验的主要限制，需要快速和临时地将约20个研究中心上线，以满足招募目标。因此，拟议中的研究与NIH使命的一部分有关，即通过发展和加速生物医学技术的应用来改善健康。在强大的初步数据的指导下，我们的设计方法依赖于两个特定的目标：1）开发一个标准平台，用于操作和测试各种新的光学单元设计，以及2）通过优化光子效率来开发增强的光学单元几何结构。实现这些目标将：a）在129 nm偏振器中提供一种全新的和改进的有效光泵浦方法，B）直接测量这种新设计的关键性能特征，以最大化偏振水平和吞吐量，以及c）开发使这种产品商业化所需的集成控制和监测包。所提出的方法是创新的，因为它采用了一种全新的光学单元设计方法，将减少超偏振技术的尺寸和设施占地面积，同时提高其性能。这项拟议的研究意义重大，因为这种技术的实现将大大加速超极化129 α作为慢性肺病治疗临床试验中的生物标志物的部署。

DESCRIPTION (provided by applicant): There are now 50+ new drugs in Phase II-III development to treat COPD - a disease affecting 13 million Americans, costing $49B and killing 120,000 each year. However, a major limitation in evaluating therapies for these chronic diseases is the lack of a sufficiently sensitive and non-invasive method for drug developers to see efficacy on timescales of days rather than months. Without such methods, expensive drug development programs fail, and promising new drugs are never put into trials. An emerging solution is hyperpolarized 129Xe MRI, which is an extraordinarily powerful marker of regional pulmonary function and therapy response. However, its availability in major pulmonary centers is currently limited. Our long-term goal is to build a business that can broadly deploy non-invasive, high-resolution hyperpolarized 129Xe MRIs as a biomarker to help accelerate evaluation of promising therapies for respiratory diseases. The objective of this application is to improve the size, conversion efficiency, and hence the economics of the optical cell within 129Xe polarizers. The critical need is that today's hyperpolarization technology is relatively inefficient in converting laser power into spin-polarized 129Xe. Over 80% of the available laser power is not productively converted into spin polarization. Adding additional laser power and optical cell volume to overcome conversion inefficiency results in large, expensive units that must be installed in a dedicated room, with a source of compressed air, external gas cylinders, and 3-phase power in close proximity to the MRI scanner. The rationale for the proposed project is that by using a novel optical cell geometry, it will become possible to produce highly polarized 129Xe in a small, compact, economical system employing modest laser power and requiring nothing unusual of the facility. By solving this critical bottleneck, we remove major limitations fr clinical trials requiring ~20 sites to be brought on line quickly and temporarily to meet recruitment targets. Thus, the proposed research is relevant to that part of the NIH Mission that pertains to improving health by developing and accelerating the application of biomedical technologies. Guided by strong preliminary data, our design approach relies on two Specific Aims: 1) Develop a standard platform for operating and testing various new optical cell designs, and 2) Develop enhanced optical cell geometry by optimizing photon efficiency. Completion of these aims will: a) deliver a fundamentally new and improved approach to efficient optical pumping in 129Xe polarizers, b) directly measure the key performance characteristics of this new design to maximize polarization levels and throughput, and c) develop the integrated control and monitoring package needed to commercialize such a product. The proposed approach is innovative because it takes a fundamentally new approach to optical cell design that will reduce the size and facility footprint of hyperpolarization technology while improving it performance. The proposed research is significant because realization of such technology will greatly accelerate the deployment of hyperpolarized 129Xe as a biomarker in clinical trials for chronic lung disease therapies.