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

描述（由申请人提供）：最近，CDC宣布COPD已升级为该国第三大死亡原因。John沃尔什（COPD基金会主席）评论说：“COPD从第四大病因上升到第三大病因的时间比最初预计的要早12年，这是不可接受的。“尽管在护理方面取得了重大进展，但COPD流行病仍然存在，每年导致超过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中继续存在的严重知识差距。 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非侵入性MR生物标志物对肺功能进行定性和定量区域评价。这个项目的意义在于如果我们能检测到肺部的区域变化， 如果在整体通气量变化（例如，肺量计测量）或临床症状（例如，恶化）之前确定肺容量和功能，则我们可以在肺的受影响区域仍然“可恢复”时进行治疗干预。未满足的临床需求是目前的标准治疗 肺部疾病的诊断和评估几乎完全依赖于全局PFT信息（基本上是“单一体积”元素，整个连通气道系统），并且诊断和治疗的改进取决于可在适度的技术影响和成本下部署的更好的和区域性的肺部成像策略。 我们已经证明，可呼吸氟化气体（PFx）提供了一个全新的和廉价的基于MR的方法，在人体三维通气成像。我们的初步工作表明，这些药物耐受性良好;能够实现成像通气，其质量与天然丰度超极化129 MRI相似。中心假设和当前观察结果是，用作造影剂的PFx气体提供肺气道的功能图像，包括重要的局部通气信息，例如通气缺陷严重程度和气体捕获。我们将检验中心假设，并通过解决以下目标实现总体目标：1）确定肺通气（包括气体捕获）的定量指标，2）定义通气缺陷的严重程度，3）在充分表征的受试者队列中比较PFx成像与HRCT的气体捕获。 技术创新包括使用单次呼吸非平衡成像和多次呼吸平衡成像技术，不仅可以评估“静态”通气缺陷，还可以评估通气缺陷的严重程度。工作成果包括 一种用于评估人类局部肺功能的新方法，该方法不使用电离辐射，并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.