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

描述(由申请人提供)：目前有50多种新药处于第二-第三阶段开发中，用于治疗COPD-一种影响1300万美国人的疾病，每年耗资490亿美元，导致12万人死亡。然而，评估这些慢性疾病的治疗方法的一个主要限制是缺乏一种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看到疗效。如果没有这样的方法，昂贵的药物开发计划就会失败，有希望的新药永远不会投入试验。一个新兴的解决方案是超极化129Xe MRI，它是一个非常强大的局部肺功能和治疗反应的标志物。然而，目前它在主要肺中心的可获得性有限。我们的长期目标是建立一家能够广泛部署非侵入性、高分辨率超极化129Xe磁共振成像作为生物标志物的业务，以帮助加快对有前景的呼吸系统疾病治疗方法的评估。此应用程序的目标是 改进129Xe偏振器内的光学单元的大小、转换效率，从而提高经济性。迫切需要的是，今天的超极化技术在将激光能量转化为自旋极化的129Xe方面效率相对较低。超过80%的可用激光功率没有有效地转化为自旋极化。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的问题，导致大型昂贵的设备必须安装在专用房间中，压缩空气源、外部气瓶和三相电源非常接近MRI扫描仪。提议的项目的基本原理是，通过使用一种新的光学单元几何结构，将有可能产生高度偏振的 129Xe是一个小型、紧凑、经济的系统，使用适度的激光功率，对设备没有什么不寻常的要求。通过解决这一关键瓶颈，我们消除了临床试验的主要限制，临床试验需要快速和临时地上线约20个地点，以满足招募目标。因此，拟议的研究与NIH任务中有关通过开发和加快生物医学技术的应用来改善健康的部分相关。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)开发一个操作和测试各种新的光学单元设计的标准平台，2)通过优化光子效率来开发增强的光学单元几何结构。这些目标的实现将：a)为129Xe偏振器的高效光泵浦提供一种全新的改进方法；b)直接测量这一新设计的关键性能特性，以最大限度地提高偏振水平和吞吐量；以及c)开发将此类产品商业化所需的集成控制和监控组件。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，将减少超极化技术的尺寸和设施占用空间，同时提高其性能。这项拟议的研究具有重要意义，因为这种技术的实现将极大地加快超极化129Xe作为生物标志物在慢性肺部疾病治疗临床试验中的部署。

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.