Human Lung Regional Ventilation Defect Severity Measured by Fluorine-19 Gas MRI

描述(申请人提供)：最近，美国疾病控制与预防中心宣布，慢性阻塞性肺病已上升至该国第三大死因。约翰·沃尔什(慢性阻塞性肺病基金会主席)评论说：“令人无法接受的是，慢性阻塞性肺病比最初预计的提前12年从第四位上升到第三位。”尽管在护理方面取得了重大进展，但慢性阻塞性肺病的流行仍然存在，导致每年超过12万人死亡。仅在美国。这强调了在一般肺功能的检测和评估方面仍然存在的严重的知识差距。本研究项目的总体目标是开发和验证使用全氟气体作为通气造影剂的基于非侵入性MR的生物标志物对肺功能的定性和定量区域评估。这个项目的意义在于，如果我们能检测到肺部的区域差异 在全球通气量和功能发生变化(例如，肺活量测定)或临床症状(例如，病情恶化)之前，我们可以在受影响的肺区域仍然“可恢复”的情况下进行治疗干预。未得到满足的临床需求是目前的护理标准 对于肺部疾病的诊断和评估几乎完全依赖于全球PFT信息(基本上是一个“单一容量”要素，即整个沟通的呼吸道系统)，而诊断和治疗的改进取决于更好的区域性肺部成像战略，这些战略可部署，技术影响和成本适中。我们已经证明，可呼吸氟化气体(PFX)为人类3D通风成像提供了一种全新的、廉价的基于MR的方法。我们的初步工作表明，这些制剂具有良好的耐受性；使成像通风的质量与自然丰富的超极化129Xe磁共振成像相似。中心假设和目前的观察是，作为造影剂的PFX气体提供了肺通道的功能图像，包括重要的区域通风信息，如呼吸缺陷的严重程度和气体捕获。我们将验证中心假设，并通过解决以下目标来实现总体目标：1)确定包括气体捕获在内的肺通气量的定量测量；2)定义呼吸缺陷的严重程度；3)在具有良好特征的受试者队列中比较来自PFX成像的气体捕获与HRCT。这些技术创新包括使用单次呼吸非平衡成像和多呼吸平衡成像技术，不仅可以评估静态通风缺陷，还可以评估通风缺陷的严重程度。这项工作的成果包括 一种评估人类局部肺功能的新方法，它不使用电离辐射，而且比超极化技术更容易传播。

DESCRIPTION (provided by applicant): Recently, the CDC announced that COPD had escalated to the 3rd leading cause of death in this country. John Walsh (President, COPD Foundation) remarked that "It's unacceptable that COPD has gone from the fourth leading cause to the third twelve years sooner than what was originally projected." Although there have been significant advances in care, the COPD epidemic persists, leading to more than 120,000 deaths/yr. in the US alone. This emphasizes the serious knowledge gap that continues to exist in the detection and evaluation of general lung function. The overall goal of this research project is to develop and validate both qualitative and quantitative regional evaluation of lung function with non-invasive MR based biomarkers using perfluorinated gases as ventilation contrast agents. The significance of this project is if we could detect regional variations in lung volume and function prior to global ventilation changes (e.g. spirometric measures) or clinical symptoms (e.g. exacerbations), we could perform therapeutic interventions while the affected area of the lung is still 'recoverable'. The unmet clinical need is that currently Standard of Care for diagnosis and evaluation of lung disease relies nearly exclusively on global PFT information (essentially a 'single volume' element, the entire communicating airway system) and that improvements in diagnosis and treatment depend on better and regional strategies for lung imaging that are deployable with moderate technical impact and cost. We have already shown that breathable fluorinated gases (PFx's) provide an entirely new and inexpensive MR-based approach to 3D ventilation imaging in humans. Our preliminary work has shown that these agents are well tolerated; enable imaging ventilation with a quality similar to that of natural abundance hyperpolarized 129Xe MRI. The central hypothesis and current observation is that PFx gases used as contrast agents provide functional images of the lung airways including important regional ventilation information such as ventilation defect severity and gas trapping. We will test the central hypothesis and accomplish the overall objective by addressing the following aims 1) determine quantitative measures of lung ventilation including gas trapping, 2) define ventilation defect severity and 3) compare gas trapping from PFx imaging to HRCT in a well characterized subject cohort. The technical innovations include the use of single-breath non-equilibrium imaging and multi-breath equilibrium imaging techniques to evaluate not only 'static' ventilation defects but also ventilation defect severity. The outcomes of the work include a novel approach for evaluation of regional lung function in humans that does not use ionizing radiation and is more easily disseminated than hyperpolarized technology.