Compartment-selective XTC MRI in Humans

描述（由申请人提供）：尽管肺部疾病的死亡率和发病率很高，但它们通常难以诊断和表型，特别是在早期，可能更好的治疗阶段。对于儿童肺部疾病，这种情况变得更加令人信服，因为肺部的主要成像方式使儿童暴露于电离辐射，儿童比成人对辐射更敏感。因此，超极化气体MRI可能特别适合评估儿童镰状细胞患者的哮喘、囊性纤维化（CF）、支气管肺发育不良（BPD）或肺部病理。在这个程度上，我们建议推进氙偏振转移对比（XTC） MRI的方法和所需的超极化氙-129 （HXe129）的分布能力。XTC MRI在其目前的实施只能表征肺组织和肺泡空气空间之间的气体交换过程。然而，我们假设额外的改进和使用高达3t的磁场强度将允许新的光谱选择性，首次在人类中区分空气空间和薄壁组织之间的交换与空气空间和红细胞之间的交换。这样的改进将允许相当高的敏感性病理变化和更好的疾病表型。这些努力将通过将Xemed的便携式临床偏光器原型暂时转移到费城儿童医院来完成。这种具有成本效益的方法可以满足超偏光氙气MRI的科学基础设施要求，这将降低许多寻求获得世界级氙气偏光器的研究小组的成本障碍。氙气偏振转移对比（XTC） MRI已被证明是一种很有前途的工具，通过检测肺实质和肺泡空气间隙之间正在进行的气体交换过程来测量肺功能。在本建议中，我们建议将该技术扩展到监测空气空间和两个可区分的溶解相区室（红细胞和肺组织本身）之间的气体交换，温度分别为1.5 T和3 T。将这些进步与大量高极化氙-129的可用性相结合，将允许进行一系列极具针对性的非侵入性肺功能测试，而无需使用电离辐射或放射性示踪剂。这可以在5-6秒的屏气内进行。由于这种操作通常甚至可以由患有严重肺部疾病的患者或幼儿进行，因此由此产生的产品将对制药工业产生巨大的兴趣，用于开发治疗肺部疾病的新药和长时间监测治疗。

DESCRIPTION (provided by applicant): Despite the high mortality and morbidity of lung diseases, they are frequently difficult to diagnose and phenotype, especially in the early, potentially better treatable stages. For childhood lung disease, the case becomes even more compelling because the primary imaging modalities for the lung expose the child to ionizing radiation, and children are more radiation sensitive than adults. Thus, hyperpolarized gas MRI might be particularly suitable to assess asthma, cystic fibrosis (CF), bronchopulmonary dysplasia (BPD) or pulmonary pathology in sickle cell patients in children. To this extent we propose to advance the methodology of Xenon polarization Transfer Contrast (XTC) MRI and the distribution capabilities of the required hyperpolarized xenon-129 (HXe129). XTC MRI in its current implementation can only characterize the gas exchange process between the lung tissue and the alveolar air spaces in general. However, we hypothesize that additional refinements and the use of magnetic field strengths up to 3 T will permit new spectral selectivity, distinguishing for the first time in humans exchange between the airspaces and parenchyma from exchange between the airspaces and red blood cells. Such an improvement would allow considerably higher sensitivity for pathological changes and better disease phenotyping. These efforts will be accomplished by temporarily relocating Xemed's portable clinical polarizer prototype to the Children's Hospital of Philadelphia. This demonstration of a cost-effective approach to meeting the scientific infrastructure requirements for hyperpolarized xenon MRI will lower the cost barrier to many research groups seeking to access a world-class xenon polarizer.Xenon polarization Transfer Contrast (XTC) MRI has been shown to be a promising tool to measure lung function through the detection of the ongoing gas- exchange processes between lung parenchyma and alveolar air spaces. In this proposal we suggest to extend the technique to monitor gas exchange between the air spaces and the two distinguishable dissolved-phase compartments, the red blood cells and the lung tissue itself, at 1.5 T and 3 T. Combining these advances with the availability of large quantities of highly polarized xenon-129 will permit the performance of a series of extremely targeted, non-invasive lung function tests, without employing ionizing radiation or radioactive tracers, that could be conducted within 5-6 6s breath holds. Since such maneuvers can usually be performed even by patients with severe lung disease or young children the resulting product would be of tremendous interest to the pharmaceutical industry for the development of novel drugs for pulmonary diseases and the monitoring of treatment over extended periods of time.