Hyperpolarized 129Xe Imaging of Pulmonary Gas Exchange

描述（由申请人提供）：我们的总体目标是利用超极化129Xe MRI开发一种强大的肺部气体交换成像方法，该方法可用于临床和涉及气体交换异常的肺部疾病的小动物研究。我们建议显著提高我们最近展示的129Xe气体交换成像方法的分辨率和准确性，测试其检测限，将该方法与最可能的竞争对手-高分辨率CT进行比较，并将其与金标准-组织学进行比较。一种无创且有效的生物标志物可能会导致我们诊断、治疗和理解间质性肺疾病的能力发生巨大变化。本研究将在大鼠中进行，为预期的临床转化奠定基础。我们的方法使用超偏振129Xe来鉴别129Xe摄取到肺血/气屏障和红细胞的图像。与热极化相比，超极化使129Xe MRI信号增加了5个数量级，使高分辨率气体成像成为可能。大的129Xe化学位移使我们能够在空域、血液/气体屏障和红细胞区室中区分129Xe。129Xe要到达红细胞，必须首先穿过血/气屏障。由于扩散输运次数与屏障厚度的平方成正比，因此红细胞中129Xe摄取的成像非常敏感，能够检测到屏障厚度5¿m的变化。到目前为止，对气体交换过程的直接成像还不可能通过任何方法实现。除了通气和灌注外，气体交换是肺功能最基本的方面。肺气体交换障碍发生在许多疾病中，但很难在干预最有可能有效的早期阶段明确评估。诸如肺纤维化、炎症和辐射引起的肺炎等疾病最初可能不会显著改变通气或灌注。只有当疾病非常严重时，才能通过高分辨率CT记录的密度增加来诊断明显的结构异常。提出的工作将为肺部疾病成像增加一种基础和敏感的新能力。完成所提出的工作将确保该方法将准备好转化为临床环境，并在肺部疾病的纵向评估动物模型的常规应用。提出的工作将开发一种新的非侵入性方法来成像肺气体交换异常。这对于肺纤维化等间质性肺疾病的早期诊断尤其重要。在项目完成后，该方法应准备好翻译到临床设置。

DESCRIPTION (provided by applicant): Our global aim is to develop a robust pulmonary gas exchange imaging method using hyperpolarized 129Xe MRI, which can be used clinically and in small animal research of pulmonary diseases involving gas exchange abnormalities. We propose to significantly improve the resolution and accuracy of our recently demonstrated 129Xe gas exchange imaging method, test its detection limits, compare the method to its most likely competition - high-resolution CT, and compare it to the gold standard - histology. A noninvasive and effective biomarker could lead to a dramatic change in our ability to diagnose, treat, and understand interstitial lung diseases. This research will be carried out in rats and lays the groundwork for anticipated clinical translation. Our method uses hyperpolarized 129Xe to differentially image 129Xe uptake into pulmonary blood/gas barrier and red blood cells. Hyperpolarization increases the 129Xe MRI signal by 5 orders of magnitude compared to thermal polarization, making high resolution gas imaging possible. The large 129Xe chemical shift enables us to discriminate 129Xe in airspace, blood/gas barrier, and red blood cell compartments. For 129Xe to reach the red blood cells, it must first traverse the blood/gas barrier. Since diffusive transport times scale as the square of barrier thickness, imaging of 129Xe uptake in red blood cells is exquisitely sensitive and capable of detecting 5¿m changes in barrier thickness. Until now, direct imaging of the gas exchange process has not been possible by any method. In addition to ventilation and perfusion, gas exchange is the most fundamental aspect of lung function. Impairment of pulmonary gas exchange occurs in numerous pathologies, but is difficult to assess definitively at early stages when intervention is most likely to be effective. Diseases such as pulmonary fibrosis, inflammation, and radiation induced pneumonitis initially may not dramatically change ventilation or perfusion. Only once the disease is very advanced, can significant structural abnormalities be diagnosed via density increases noted on high-resolution CT. The proposed work will add a fundamental and sensitive new capability to pulmonary disease imaging. Completion of the proposed work will ensure that this method will be ready for translation to a clinical setting, and to the routine application in longitudinal evaluation animal models of pulmonary disease. The proposed work will develop a novel and non-invasive method for imaging pulmonary gas exchange abnormalities. It is particularly relevant for the early diagnosis of interstitial lung diseases such as pulmonary fibrosis. Upon completion of the project, the method should be ready for translation to a clinical setting.