Development of Hyperpolarized Helium for Assessing ILD

描述（由申请人提供）：特发性弥漫性肺实质疾病（DPLD）是一组通常难以区分的疾病。与炎症（即NSIP）相关的患者通常比与纤维化（即UIP）相关的患者预后更好。极化气体MRI技术从未应用于肺医学的这一领域。超极化（HP）氦核磁共振成像能够以非侵入性方式评估结构和功能，同时提供区域信息，能够彻底改变我们诊断和跟踪这些疾病的方式。HP MRI有可能测量肺纤维化的三个重要参数：肺泡大小、顺应性和肺泡氧分压。炎性弥漫性肺疾病和纤维化弥漫性肺疾病在病理学上存在重要差异，这使我们相信在这两种情况下这些测量结果是不同的。我们的假设是，纤维化肺疾病（UIP）的特征是随着气道大小的增加而降低顺应性的区域（蜂窝肺），而炎症性间质性肺疾病的特征是随着气道大小的减少而降低顺应性的区域。此外，我们假设纤维化肺病的蒸馏气道会相对维持肺泡O2水平，而炎症性间质性肺病的蒸馏气道/肺泡O2水平会降低。我们的计划是开发小动物HP MRI技术，以便我们可以将这些技术应用于DPLD的评估和诊断。我们将在健康大鼠中使用HP氦MRI优化和评估三种区域测量技术（区域肺泡大小、肺顺应性和肺泡氧水平）的可重复性。我们将通过HP氦磁共振成像测量各组区域肺泡大小、顺应性和氧合来确定健康大鼠、炎症大鼠模型和纤维化大鼠模型之间的区域功能和结构差异。B.我们将HP MRI测量值与肺功能障碍的标准化测量值进行比较，后者包括MRI前肺功能测试、MRI后大鼠肺组织病理学检查和胶原含量测量。公共卫生相关性：本研究提出的工作将解决一种病因不明的严重肺部疾病，即特发性弥漫性肺实质疾病（DPLD）。我们将首次在正常大鼠和两种DPLD大鼠模型中开发超极化氦磁共振成像技术来测量区域肺泡大小、顺应性和肺泡氧水平。我们相信这些测量可以区分炎症性和纤维化性DPLD，并且在人类中具有重要的诊断和预后效用

DESCRIPTION (provided by applicant): The idiopathic diffuse parenchymal lung disorders (DPLD) are a group of disorders that are often difficult to distinguish. Those associated with inflammation (i.e. NSIP) usually have a better prognosis than those associated with fibrosis (i.e., UIP). The techniques of polarized gas MRI have never been applied to this area of pulmonary medicine. Hyperpolarized (HP) helium MRI with its ability to assess structure and function in a non-invasive manner while giving regional information has the ability to revolutionize how we diagnose and follow these disorders. HP MRI has the potential to measure three important parameters in pulmonary fibrosis: alveolar size, compliance, and the alveolar partial pressure of oxygen. There are important differences in pathology between the inflammatory and fibrotic diffuse lung disorders that lead us to believe these measurements will be different in the two conditions. Our hypothesis is that fibrotic lung disease (UIP) will be characterized by regional areas of decreased compliance with an increase in distil airway size (honeycomb lung) in contrast to inflammatory interstitial lung disease which will be characterized by areas of decreased compliance with a decrease in distil airway size. In addition, we hypothesize that the distil airways in fibrotic lung disease will have relatively maintained alveolar O2 levels while in inflammatory interstitial lung disease the distil airway/alveolar O2 levels will be decreased. Our plan is to develop HP MRI techniques for small animals so that we can apply these techniques for the evaluation and diagnosis of the DPLD. Our specific aims are: Specific Aim 1: We will optimize and assess the reproducibility of the three regional measurement techniques (regional alveolar size, lung compliance, and alveolar oxygen levels) using HP helium MRI in healthy rats Specific Aim 2:A. We will identify regional functional and structural differences between healthy rats, an inflammatory rat model, and a fibrotic rat model by performing HP helium MRI measurements of regional alveolar size, compliance, and oxygenation in the groups. B. We will compare the HP MRI measurements with standardized measurements of lung dysfunction which will include pre-MRI pulmonary function tests, and post-MRI histopathological examination of the rat lung and measurement of collagen content. PUBLIC HEALTH RELEVANCE: The work proposed in this study will address a serious pulmonary condition of unknown etiology known as the idiopathic diffuse parenchymal lung disorders (DPLD (. We will develop for the first time in normal rats and two rat models of DPLD, hyperpolarized helium MRI techniques to measure regional alveolar size, compliance and alveolar oxygen levels. We believe that these measurements can differentiate inflammatory from fibrotic DPLD and will have important diagnostic and prognostic utility in humans