HXe Hyperpolarised Xenon Production Technology Optimization

描述（由申请人提供）：超极化氙-129 (HXe) MRI准备解决未满足需求的关键领域。为了推进更个性化的医疗，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、肺泡尺寸、摄氧量、侧枝通路、实质体积与肺泡气体体积的比例、间隔壁厚度和与红细胞的气体交换的精确成像生物标志物。一套新的氙偏光器技术是研究活动激增的主要原因。我们的UNH团队通过发明逆流极化过程，在高流量低压状态下发明了超极化氙的生产。随后的发明包括使用上升杜瓦瓶从流动气体中低温分离超极化氙，使用阶梯反射镜缩小二极管激光堆栈的光谱，以及使用多通道铜柱扩大生产输出。这些技术结合在一个原型偏振器中，在四个月的时间里，为600人的实验提供了两升30%偏振光的氙气。这一成功虽然令人印象深刻，但仍低于该技术的计算潜力：生产产量的五倍提高并没有达到偏光柱横截面的十四倍增加。临床上30%的极化远低于超过80%的潜在最大值。我们在实验室中验证过的冷冻分离，在临床中出现了不一致和偶尔的失败，减少了气体回收的数量和它的极化。我们提出了一项技术创新、诊断测试和分析评估的计划，以支持氙偏光器输出三到五次改进的另一个因素。为了提高光泵浦效率，我们将测试Rb-Cs碱混合泵浦。为了解决来自色谱柱的无法解释的极化下降，我们将评估通过在铜上附着薄铝硅酸盐涂层所实现的性能改进。为了防止部分（或全部）氙雪被吹走，我们将在雪的螺旋中引入一个细钨丝线圈，在雪融化时锚定雪。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供应高度超额认购，这更加强调了HXe作为肺功能成像药物的监管批准和商业化。该提案的批准将为领先的氙气极化学术小组继续在支撑该领域的科学和技术方面取得根本性进展提供唯一的支持。

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.