Development of Hyperpolarized Helium for Assessing ILD

描述(申请人提供)：特发性弥漫性实质性肺病(DPLD)是一组通常难以区分的疾病。与炎症相关的患者(即NSIP)通常比与纤维化相关的患者(即UIP)预后更好。极化气体磁共振成像技术从未被应用于这一肺部医学领域。超极化(HP)氦磁共振成像具有以非侵入性方式评估结构和功能的能力，同时提供区域性信息，有能力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。炎症性和纤维性弥漫性肺疾病在病理上有重要的差异，这使得我们相信这些测量在这两种情况下会有所不同。我们的假设是，与炎症性间质性肺病不同，纤维性肺病(UIP)的特点是局部顺应性降低，蒸馏气道大小增加(蜂窝肺)。炎症性间质性肺疾病的特点是顺应性降低，蒸馏气道大小减小。此外，我们假设在纤维性肺疾病中，蒸馏气/肺泡氧含量相对保持不变，而在炎症性间质性肺疾病中，蒸气/肺泡氧含量降低。我们的计划是为小动物开发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。我们的具体目标是：特定目标1：我们将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)在健康大鼠中的重复性。特定目标2：A。我们将通过对三组大鼠的区域肺泡大小、顺应性和氧合作用进行HP氦MRI测量，识别健康大鼠、炎症模型和纤维化大鼠模型之间的局部功能和结构差异。B.我们将比较HP MRI测量与肺功能障碍的标准化测量，包括MRI前的肺功能测试、MRI后的大鼠肺组织病理学检查和胶原含量的测量。公共卫生相关性：这项研究中提出的工作将解决一种原因不明的严重肺部疾病，称为特发性弥漫性实质性肺疾病(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MRI技术来测量局部肺泡大小、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性DPLD，并将对人类有重要的诊断和预后作用。

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