Quantitation of Lung Ventilation and Structure by 3He MR

描述（由申请人提供）：肺气肿是美国和世界范围内的主要医学问题。评估肺气肿的诊断方法应对肺泡水平的区域性肺结构敏感。利用超极化3He气体的扩散MRI评估3He气体ADC（表观扩散系数）可以提供这种灵敏度。它提供了传统成像方式和肺功能测试无法提供的肺微观结构和功能信息。通过3He弥散MRI，可以评估肺泡大小和肺泡壁的完整性，即使肺泡太小而无法通过直接成像解决。这表明了超极化3He气体ADC测量在临床应用中的巨大潜力。然而，直到最近，人们还不清楚3He气体ADC测量所探测的肺结构的具体特征。最近，我们提出了一个基于大量组织学数据的理论模型来提供这种解释。然而，如果我们要理解3He ADC测量并最佳地利用其诊断潜力，就必须回答一些实质性问题。在这个建议中，我们将扩展我们的数学模型，将肺各向异性ADC测量与肺微观结构参数联系起来。该数学模型是基于一个真实的肺腺泡水平结构，描述了腺泡气道覆盖肺泡套。肺内气体扩散理论是基于肺腺泡气道各向异性扩散这一关键概念。我们将对健康肺的牺牲小鼠进行复杂的多维磁共振实验，以测试我们的数学模型的基本特征，ADC的各向异性。我们将进一步开发和测试我们的新的弥散3He MRI技术，用于肺气肿犬模型的断层“肺活检”，其生理学与人类相似，并建立由CT确定的肺气肿严重程度与3He各向异性扩散率之间的定量关系。我们将使用3He扩散通气MRI结合CT对正常人和肺气肿患者进行研究。这三种技术的相互比较将建立CT、肺通气和各向异性ADC测量之间的定量关系，并将为每种模式获得的结果提供新的解释可能性。潜在的影响是巨大的。肺气肿进展的全面临床图片，从肺泡变形的初始发作到最后阶段，以肺功能的显著丧失为特征，将建立。新的方法将足够灵敏，可以早期诊断肺气肿，从而改善患者的治疗。

DESCRIPTION (provided by applicant): Emphysema is a major medical problem in the US and worldwide. Diagnostic methods for the evaluation of emphysema should be sensitive to regional lung structure at the alveolar level. Diffusion MRI with hyperpolarized 3He gas that evaluates the 3He-gas ADC (apparent diffusion coefficient) can provide this sensitivity. It offers information on lung microstructure and function not provided by traditional imaging modalities and pulmonary function tests. With 3He diffusion MRI, alveolar size and the integrity of alveolar walls can be evaluated, even though the alveoli are too small to be resolved by direct imaging. This points to the large potential for clinical application of ADC measurements with hyperpolarized 3He gas. However, until recently it was not clear what specific features of lung structure are probed by 3He gas ADC measurements. Recently we proposed a theoretical model based on a large body of histology data that provides this explanation. However, substantial questions must be answered if we are to understand the 3He ADC measurement and optimally exploit its diagnostic potential. In this proposal we will extend our mathematical model that relates anisotropic ADC measurements in lung to lung microstructural parameters. The mathematical model is based on a realistic structure of lung at the acinar level described in terms of acinar airways covered with alveolar sleeves. The theory of gas diffusion in lung is based on our key concept of anisotropic diffusion in lung acinar airways. We will conduct sophisticated multi-dimensional MR experiments on sacrificed mice with healthy lungs to test the fundamental feature of our mathematical model, the anisotropy of ADC. We will develop further and test our new diffusion 3He MRI technique for tomographic "lung biopsy" on a canine model of emphysema with physiology similar to human and establish a quantitative relationship between the severity of emphysema as determined by CT and the 3He anisotropic diffusivities. We will use 3He diffusion and ventilation MRI together with CT to study normal human subjects and patients with emphysema. Inter-comparison of these three techniques will establish quantitative relationships between CT, lung ventilation and anisotropic ADC measurements and will open up possibilities for new interpretations of results obtained by each modality. The potential implications are significant. A comprehensive clinical picture of emphysema progression, from initial onset of the alveolar deformation to the final stage, characterized by dramatic loss of lung function, will be established. New methods will be sensitive enough to allow early diagnosis of emphysema that will improve patient treatment.