APPLICATION OF HYPERPOLARIZED XENON-129 VIA THE VASCULAR SYSTEM

通过血管系统应用超极化 XENON-129

• 批准号: 8363153
• 负责人: HARALD MOLLER
• 金额: $ 1.84万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363153
• 关键词: Alveolar; Alveolus; Blood; Blood flow; Brain; Breathing; Continuous Infusion; Emulsions; Fat emulsion; Fiber; Funding; Gases; Grant; Image; Infusion procedures; Injection of therapeutic agent; Lipids; Liquid substance; Lung; Magnetic Resonance Imaging; Membrane; Methods; Microbubbles; Microscopy; National Center for Research Resources; Organ; Organism; Perfusion; Phase; Plasma; Principal Investigator; Process; Production; Research; Research Infrastructure; Resources; Saline; Solubility; Source; Stream; System; Techniques; United States National Institutes of Health; Vascular System; Veins; Venous; Water; Xenon; cost; improved; in vivo; interest; research study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. During the past decade, hyperpolarized (HP) 129Xe has found application in biomedical MRI with exciting results. Typically, the gas is introduced into the organism by inhalation, which is an efficient strategy for imaging the gas space of the lungs. Due to the alveolar gas exchange, a small amount of inhaled HP 129Xe enters the pulmonary blood and is delivered to other organs. This has already been exploited to study brain perfusion. More efficient methods for the local delivery of xenon to other target organs may include pre-dissolving of the HP gas in a suitable liquid or the production of microbubbles with subsequent injection into the blood stream. For initial experiments, we will use isotopically enriched 129Xe (82%), Intralipid 30% (Pharmacia, Clayton, NC) and a 'shaker' as described in M¿ller et al. MRM 41, 1058 (1999) to reproduce previous experiments serving as a reference. The search for other vehicles for local delivery will include dissolving of HP 129Xe in fully oxygenated blood or plasma and dissolving of HP 129Xe in deuterated saline solution. Although the solubility of xenon in these liquids is significantly less than that of lipid emulsions, they are of interest because Xe will be released to the alveolar gas phase upon passing through the lungs, which can be exploited for perfusion imaging if RF excitation is selectively applied to the gas phase resonance. In addition, such systems may be tolerated better during prolonged infusion experiments. Experiments with deuterated saline are of further interest one may expect a drasticallyprolonged 129Xe T1. Insead of the previously used 'shaker' for dissolving HP 129Xe, another strategy will involve hollow-fiber membranes to improve the process of dissolving. This technique may also hold a potential for continuous infusion of the HP gas carrier. For comparison, experiments involving direct injection of small amounts of HP 129Xe into a vein will also be investigated. Regarding the Ostwald solubility (L) of Xe in water, roughly 0.1 mL of gas may be injected per mL of blood. If f is the venous blood flow in mL/sec, HP gas may be injected continuously at a rate of L x f provided that the dissolving process is sufficently rapid in vivo and the gas is quantitatively released to the alveoli.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 在过去的十年里，超极化(HP)129Xe在生物医学核磁共振中的应用取得了令人兴奋的结果。通常情况下，气体是通过吸入进入生物体的，这是成像肺部气体空间的有效策略。由于肺泡气体交换，少量吸入的HP 129Xe进入肺血液，并被输送到其他器官。这一点已经被用来研究大脑的灌注。将氙气局部输送到其他靶器官的更有效的方法可能包括将高压气体预先溶解在合适的液体中或产生微泡并随后注入血液中。在最初的实验中，我们将使用同位素浓缩的129Xe(82%)、Intralipid 30%(法玛西亚，克莱顿，北卡罗来纳州)和M？ler等人描述的摇床。MRM 41,1058(1999)以再现以前的实验作为参考。寻找其他本地递送的载体将包括将Hp 129Xe溶解在全氧血液或血浆中，以及将Hp 129Xe溶解在氚盐溶液中。虽然Xe在这些液体中的溶解度明显低于脂肪乳剂，但它们很有意义，因为Xe在通过肺部时将被释放到肺泡气相，如果有选择地将RF激发应用于气相共振，则可以利用这一点进行灌注成像。此外，在长时间的输液试验中，这种系统的耐受性可能更好。人们更感兴趣的是用氚盐进行的实验，人们可能会预计129Xe的T1会显著延长。除了以前使用的溶解Hp 129Xe的摇床外，另一种策略将涉及中空纤维膜来改进溶解过程。这项技术也可能保持持续输注高压气体载体的潜力。 为了进行比较，还将研究将少量HP 129Xe直接注入静脉的实验。关于Xe在水中的奥斯特瓦尔德溶解度(L)，每毫升血液大约可以注入0.1毫升气体。如果f是静脉血流量，单位为毫升/秒，则可以L×f的速率连续注射HP气体，前提是体内溶解过程足够快，并将气体定量释放到肺泡。