HXe Hyperpolarised Xenon Production Technology Optimization

描述(由申请人提供)：超极化氙气-129(HXE)磁共振成像准备解决关键领域的未得到满足的需求。为了推动更个性化的医学，研究人员正在验证肺部在疾病诊断、严重程度分期、管理治疗和评估结果方面的应用。为了支持药物开发试验，研究人员正在验证区域通气量、肺泡大小、摄氧量、侧支循环、实质体积与肺泡气体体积的比率、隔壁厚度以及与红细胞的气体交换的精确成像生物标志物。一套新的氙气偏振器技术在很大程度上导致了研究活动的激增。我们的UNH团队发明了逆流极化过程，从而在高流量、低气压条件下产生了超极化氙气。随后的发明包括使用上升杜瓦从流动气体中低温分离超极化氙气，使用阶梯式反射镜缩小半导体激光堆栈的光谱范围，以及使用多通道铜柱扩大生产输出。这些技术被结合在一个原型偏振器中，该偏振器在四个月的时间里为600个人体受试者实验生产了两升30%偏振度的氙气。尽管这一成功可能令人印象深刻，但仍达不到该技术计算出的潜力：生产产量的五倍提高没有达到偏振片柱横截面增加十四倍。在临床上提供的30%的极化远远低于超过80%的潜在最大值。我们在实验室中验证的冷冻分离在临床上遇到了不一致和偶尔的失败，既减少了回收的气体数量，也减少了气体的极化。我们提出了一项技术创新、诊断测试和分析评估计划，以支持氙气偏振器输出提高三到五个因素的另一个因素。为了提高光泵浦效率，我们将测试Rb-Cs碱混合用于混合泵浦。为了解决柱子产生的无法解释的极化下降，我们将评估通过在铜上附着一层薄薄的铝硅酸盐涂层所获得的性能改进。为了防止部分(或全部)氙气雪从冻结中被吹走，我们将在螺旋中引入一个细小的钨丝线圈来在解冻时锚定雪。为了加速解冻，我们将评估隔膜泵控制氙气压力的操作方案。最近认识到3He的供应被高度超额认购，重点是验证HXE作为肺功能显像剂的监管批准和商业化。这项提议的批准将为领先的氙极化学术小组继续在支撑这一领域的科学和技术方面取得根本性进展提供唯一的支持。 公共卫生相关性：超极化氙气-129(HXE)磁共振成像准备解决肺功能成像中的关键领域，既作为一种管理患者的成像方式，也作为药物试验的药物开发工具。最近，偏光镜技术的一系列新技术突破使研究激增，但我们的测量和计算表明，性能改进的巨大潜力仍然存在。我们建议实施几项新技术，以便在极化和输出方面获得三到五倍的额外改善，并提高一致性和可靠性。

DESCRIPTION (provided by applicant): Hyperpolarized xenon-129 (HXe) MRI is poised to address critical areas of unmet need. Toward advancement of more personalized medicine, researchers are validating pulmonary applications in disease diagnosis, severity staging, managing treatments, and evaluating outcomes. In support of drug development trials, researchers are validating precise imaging biomarkers for regional ventilation, alveolar dimension, oxygen uptake, collateral pathways, the ratio of parenchyma volume to alveolar gas volume, septal wall thickness, and gas exchange to red blood cells. A suite of new xenon polarizer technologies is largely responsible for this surge in research activity. Our UNH team originated the production of hyperpolarized xenon in the high-flow low-pressure regime by inventing the counter-flow polarization process. Subsequent inventions included cryogenic separation of hyperpolarized xenon from flowing gases using a rising dewar, spectral narrowing of diode laser stacks using a stepped- mirror, and scale up of production output using a multi-channel copper column. These technologies were combined in a prototype polarizer that produced batches of two liters of 30% polarized xenon for 600 human subject experiments over a four month period. This success impressive though it may be, nevertheless fell short of the calculated potential of the technique: the factor of five improvement in production output did not reach the factor of fourteen increase in the polarizer column cross-section. The 30% polarization delivered in the clinic is well below the potential maximum of over 80%. The freeze-out separation that we had validated in the lab, suffered inconsistencies and occasional failures in the clinic, reducing both the quantity of gas recovered as well as its polarization. We propose a program of technological innovations, diagnostic tests, and analytical evaluations to support another factor of three-to-five improvement in xenon polarizer output. To increase optical pumping efficiency we will test Rb-Cs alkali mix for hybrid pumping. To address the unexplained drop in polarization coming from the column we will evaluate performance improvements achieved by attaching a thin aluminosilicate coating to the copper. To prevent partial (or total) losses of xenon snow being blown from the freeze-out, we will introduce a fine tungsten wire coil into the helixes to anchor the snow while thawing. To accelerate thawing we will evaluate operational scenarios for a diaphragm pump to control the xenon pressure. The recent recognition that 3He supplies are highly oversubscribed focuses greater emphasis on validating HXe for regulatory approval and commercialization as an agent for pulmonary functional imaging. Approval of this proposal would provide the only support to the leading xenon polarization academic group to continue making fundamental advances to the science and technology underpinning this field. PUBLIC HEALTH RELEVANCE: Hyperpolarized xenon-129 (HXe) MRI is poised to address critical areas of need in pulmonary functional imaging, both as an imaging modality for managing patients as well as a drug development tool for pharmaceutical trials. A series of new technological breakthroughs in polarizer technology have recently enabled a surge in research, however our measurements and calculations indicate a vast untapped potential of performance improvements can still be accessed. We propose to implement several new technologies in order to gain an additional factor of three-to-five improvement in polarization and output, and improved consistency and reliability.