Development of Airway Imaging Using HP 3He MRI

描述(由申请人提供)： 从历史上看，肺通风一直很难想象。虽然其他成像方式提供了对呼吸道解剖和反应性(例如MDCT)或通气性(例如动态CT、包括PET的放射性核成像)的洞察，但到目前为止只有CT可以结合结构和功能的视图。然而，相关的辐射，特别是在儿童中，正在推动对替代方法的探索。我们小组的独特工作构成了这一努力的重要组成部分，以限制辐射暴露，同时提高我们描述肺通风结构和功能机制的能力。为此，我们建议建立HP 3He MRI作为一种临床安全的成像方式，使我们能够可视化呼吸功能和呼吸道收缩。然而，关于我们使用这种方式量化结构和功能的能力仍然存在一些挑战。随着成像进入肺的定量区域功能评估领域，我们努力将HP 3He MRI作为可接受的替代方案或作为当前CT技术的补充手段，时机再好不过了。 我们进一步建议将HP 3He MRI与敏感的气道功能测量相结合，以确定与哮喘相关的特定收缩条件。我们将验证这一假设，即HP 3He MRI提供与MDCT相似的气道分辨率，以及额外的功能呼吸信息。这将需要1)优化我们目前的动态HP 3He MRI方法，以获得高分辨率的呼吸道图像；2)开发HP 3He MR图像的气道和通风量化方法；3)计算健康和哮喘受试者的HP 3He MRI气道直径；4)将这些测量结果与MDCT肺部成像和三维气道重建获得的结果进行比较。然后，我们将检验这一假设，即哮喘患者的气道收缩是高度异质性的，主要特征是小气道内的气道关闭，而且随着哮喘严重程度的增加，深吸气期间的气道扩张会减弱。 具体地说，我们将使用超极化(HP)3He磁共振成像系统地研究乙酰甲胆碱激发前后健康和哮喘肺的肺气道狭窄和扩张的独特性质，并作为首要目标，识别其对哮喘诊断和治疗的意义。我们还将研究动态肺阻力和弹性的频率依赖性，并计算正常呼吸和深吸气时的呼吸道阻力。最后，我们将把呼吸道收缩和换气的结构缺陷与功能缺陷联系起来。 至少，成功的概念验证将确立HP 3He MRI作为MDCT的重要补充。事实上，通过提供功能信息以及与MDCT相当的呼吸道分辨率，所有这些都不需要辐射暴露，我们相信使用HP 3He MRI最终将改善哮喘从诊断到治疗到提高生活质量的各个领域的管理。

DESCRIPTION (provided by applicant): Historically, lung ventilation has been difficult to image. Although other imaging modalities provide insight into airway anatomy and reactivity (e.g., MDCT) or ventilation (e.g., dynamic CT, radio-nuclear imaging including PET), to date only CT can combine a view of both structure and function. However, the associated radiation, particularly in children, is driving a search for alternative methodologies. The unique work of our group forms an essential part of this effort to limit radiation exposure while improving our ability to depict the structural and functional mechanics of lung ventilation. To this end, we propose to establish HP 3He MRI as a clinically safe imaging modality that enables us to visualize ventilation function and airway constriction. However, a number of challenges regarding our ability to quantitate structure and function using this modality remain. As imaging moves into the arena of quantitative regional functional assessment of the lung, our drive to establish HP 3He MRI as an acceptable alternative or as a complimentary modality to current CT technologies could not be better timed. We further propose to combine HP 3He MRI with sensitive measures of airway function to determine the specific constriction conditions associated with asthma. We will test the hypothesis that HP 3He MRI provides similar airway resolution to MDCT, as well as additional functional ventilation information. This will entail 1) optimizing our current dynamic HP 3He MRI methodology to obtain high-resolution images of the airways; 2) developing both airway and ventilation quantification methods for the HP 3He MR images; 3) calculating HP 3He MRI airway diameters for both healthy and asthmatic subjects; and 4) comparing these measurements to those obtained from MDCT lung imaging and 3D airway reconstruction. We will then test the hypothesis that airway constriction in asthmatics is highly heterogeneous and is primarily characterized by airway closures in the small airways, and that airway dilation during a deep inspiration is diminished with increased asthma severity. Specifically, we will systematically investigate the distinctive nature of pulmonary airway narrowing and expansion in healthy versus asthmatic lungs both pre- and post-methacholine challenge using hyperpolarized (HP) 3He MRI and, as an overarching objective, discern its implication for the diagnosis and treatment of asthma. We will also investigate the frequency dependence of dynamic lung resistance and elastance and calculate the airway resistance during both normal breathing and a deep inspiration. Finally, we will correlate structural defects in airway constriction and ventilation with functional defects. At a minimum, successful proof-of-concept will establish HP 3He MRI as an important complement to MDCT. Indeed, by offering both functional information as well as a degree of airway resolution comparable to MDCT, all without the need for radiation exposure, we are confident the use HP 3He MRI will ultimately lead to improved asthma management across the spectrum--from diagnosis to treatment to enhanced quality of life.