HXe Hyperpolarised Xenon Production Technology Optimization

HXe超极化氙气生产技术优化

• 批准号: 8367624
• 负责人: F. WILLIAM HERSMAN
• 金额: $ 41.99万
• 依托单位: UNIVERSITY OF NEW HAMPSHIRE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-13 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8367624
• 关键词: Address; Alkali Metals; Alkalies; Alveolar; Am 80; Area; Asthma; Automation; Biological Markers; Cesium; Chest; Chronic Obstructive Airway Disease; Clinic; Clinical; Copper; Custom; Cystic Fibrosis; Data Set; Development; Diagnostic; Diagnostic tests; Dimensions; Doctor of Philosophy; Drops; Elements; Energy Transfer; Engineering; Environmental air flow; Erythrocytes; Evaluation; Exercise; Failure; Freezing; Functional Imaging; Gases; Generations; Glass; Hawks; Heating; Hour; Hybrids; Image; Investigation; Lasers; Licensing; Lung; Magnetic Resonance Imaging; Measurement; Medical; Medicine; Modification; New Hampshire; Optics; Outcome; Output; Oxygen; Pathway interactions; Patients; Performance; Pharmacologic Substance; Phase; Process; Production; Protocols documentation; Pump; Relaxation; Reproducibility; Research; Research Activity; Research Personnel; Resources; Respiratory Diaphragm; Rubidium; Scheme; Science; Series; Severities; Sickle Cell Anemia; Site; Snow; Staging; Students; System; Techniques; Technology; Temperature; Testing; Thick; Tungsten; Universities; Virginia; Width; Xenon; aluminosilicate; base; commercialization; cryogenics; disease diagnosis; drug development; falls; healthy volunteer; human subject; imaging modality; improved; innovation; insight; new technology; pressure; prevent; programs; prototype; pulmonary agents; research study; scale up; simulation; success; surface coating; technological innovation; tool; uptake

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.

描述（由申请人提供）：超极化氙-129（HSVN）MRI准备解决未满足需求的关键领域。为了推进更加个性化的医学，研究人员正在验证肺部在疾病诊断、严重程度分期、治疗管理和结局评估中的应用。为了支持药物开发试验，研究人员正在验证精确的成像生物标志物，用于区域通气，肺泡尺寸，氧摄取，侧支通路，实质体积与肺泡气体体积的比率，间隔壁厚度和红细胞的气体交换。一套新的氙偏振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开始生产超极化氙。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，使用阶梯反射镜使二极管激光器堆的光谱变窄，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，该偏振器在四个月的时间内为600名人类受试者的实验生产了两升30%偏振氙。这一成功虽然令人印象深刻，但仍然没有达到该技术的计算潜力：生产产量的五倍提高没有达到偏振器柱横截面的十四倍增加。在临床中提供的30%极化远低于超过80%的潜在最大值。我们在实验室中验证的冷冻分离在临床中遭受不一致和偶尔的失败，减少了回收的气体量及其极化。我们提出了一个技术创新，诊断测试和分析评估的计划，以支持另一个因素的三到五个改善氙偏振器的输出。为了提高光泵浦效率，我们将测试混合泵浦的Rb-Cs碱混合物。为了解决无法解释的极化下降来自列，我们将评估通过将薄铝硅酸盐涂层附着到铜实现的性能改进。为了防止部分（或全部）损失的氙雪被吹从冻结出来，我们将引入一个细钨丝线圈到螺旋锚雪，而解冻。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，3 He供应是高度超额认购的重点更加强调验证HdR作为肺功能成像剂的监管批准和商业化。该提案的批准将为领先的氙偏振学术团体提供唯一的支持，以继续为支撑该领域的科学和技术取得根本性进展。 公共卫生相关性：超极化氙-129（HPLOY）MRI有望解决肺功能成像的关键需求领域，既作为管理患者的成像模式，也作为药物试验的药物开发工具。最近，偏振器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，仍然可以获得巨大的未开发的性能改进潜力。我们建议实施几项新技术，以获得三到五个因素的极化和输出的改善，并提高一致性和可靠性。