Hyperpolarized Xenon-129 production system for magnetic resonance imaging of the lung

肺部疾病，包括慢性阻塞性肺疾病(COPD)、哮喘和急性肺损伤(ALI)，是加拿大人的第四大死因，预计到2020年将占所有死亡人数的三分之一，给加拿大人带来巨大的社会和经济负担。迫切需要开发新的肺部成像方法，以提供：(I)更早的检测，(Ii)对疾病机制的基本洞察，以及(Iii)治疗反应的新方法，以帮助药物开发。对特别准备的(即超极化的)和吸入的惰性气体，特别是氦-3和氙气-129的磁共振成像，提供了一种令人兴奋的新方法，通过提供高达100,000倍的信号来阐明肺部。这提供了一种高度敏感和非侵入性的方法来获得肺部疾病的新的区域性指标，从而使肺部成像发生了革命性的变化。不幸的是，氦-3是一种极其稀有的氦同位素，最近全球氦-3气体短缺促使需要这项提议中所要求的设备。有了这台新设备，我们预计在来年将我们的研究计划从氦-3过渡到氙气-129。氙气-129可以像氦-3一样超极化，在大气中的丰度几乎是无限的，而且可以以很小的成本获得。人们普遍预计，氙气-129将成为未来这种强大的肺部成像方法的途径，特别是在广泛的临床应用中。这项提案要求提供资金购买必要的设备，包括定制的氙气-129超极化系统，能够满足我们正在进行的NSERC和CIHR资助的研究计划的需求。具体地说，这项要求包括：(1)150瓦窄频半导体激光器；(2)定制玻璃盒和热管理系统；(3)相关传感器和控制设备；(4)定制永久磁铁。该设备将在动物身上进行组装和测试，以生产足够质量和数量的超极化气体，以确保我们的肺成像研究计划在第一年年底顺利过渡到氙气-129。

Lung diseases, including chronic obstructive pulmonary disease (COPD), asthma and acute lung injury (ALI), are the fourth leading cause of death of Canadians and are expected to result in a third of all deaths by 2020, placing an enormous societal and economic burden on Canadians. There is a critical need to develop new lung imaging methods to provide: (i) earlier detection, (ii) fundamental insight into disease mechanisms and (iii) novel measures of therapeutic response to aid drug development. Magnetic Resonance (MR) imaging of specially-prepared (i.e. hyperpolarized) and inhaled inert gases, specifically helium-3 and xenon-129, offers an exciting new approach to elucidate the lung by providing an increase in signal of up to a factor of 100,000. This has revolutionized lung imaging by providing a highly sensitive and non-invasive method to obtain new regional indicators of lung disease. Unfortunately, helium-3 is an exceedingly rare isotope of helium and a recent global shortfall in helium-3 gas motivates the need for the equipment requested in this proposal. With this new equipment, we anticipate transitioning our research program away from helium-3 toward xenon-129 in the coming year. Xenon-129 can be hyperpolarized similarly to helium-3, is virtually limitless in its abundance in the atmosphere and can be procured at a fraction of the cost. It is widely foreseen that xenon-129 will be the pathway for this powerful lung imaging method in the future, particularly for wide-spread clinical application. This proposal requests funding to purchase the necessary equipment comprising a custom-built xenon-129 hyperpolarization system capable of meeting the needs of our on-going NSERC and CIHR-funded research program. Specifically, this request includes: (i) 150 W frequency-narrowed diode laser, (ii) custom glass-cell and thermal management system, (iii) associated sensors and control equipment and (iv) custom-built permanent magnet. The equipment will be assembled and tested in animals for the production of both sufficient quality and quantity of hyperpolarized gas to ensure a smooth transition of our lung imaging research program to xenon-129 by the end of Year 1.