Lung parenchyma loss in smokers measured with HyXeMRI

描述（由申请人提供）：由于年龄，更重要的是吸烟而导致的肺组织的持续损失，只有当实质破坏的程度因阻碍气体交换而限制代谢率时才会表现为症状。目前还没有明确的诊断方法来评估早期发现的组织损失。我们建议开发一种可以定量测量吸烟者肺组织微观结构的新指标。本研究可用于观察早期肺气肿的发病情况，验证肺气肿干预措施的安全性和有效性。超偏光氙气（HyXe） MRI最近被我们的合作伙伴证明可以在几微米尺度上对区域肺泡肺表面积进行精确敏感的测量。通过使用氙化学位移来区分溶解在组织中的氙和气相中的氙，我们观察到相交换的时间增加取决于交换时间的平方根。溶解信号与气体信号的比值与薄壁分配系数和平均面体积比成正比。饱和时间显示了组织扩散常数对薄壁厚度（平方）的缩放。我们建议测量吸烟者的肺表面积与包年相关。在第一阶段，我们将测量20名吸烟史超过20包年的受试者和10名年龄和性别匹配的健康成年人。将对数据进行分析，以确定男性和女性的平均肺表面积相关性。在第二阶段，我们将扩大研究统计，纳入更多的吸烟者，并重新测量原始受试者，以确定纵向研究中组织随时间的损失。

DESCRIPTION (provided by applicant): The continuous loss of lung tissue as a result of age, and more importantly smoking, only manifests as symptoms when the degree of parenchyma destruction limits metabolic rate by frustrating gas exchange. There is currently no clear diagnostic methodology by which early detection of tissue loss can be assessed. We propose to develop a new metric that can quantitatively measure lung tissue microstructure in smokers. This study could be useful for observing the onset of early emphysema and validating the safety and efficacy of emphysema interventions. Hyperpolarized xenon (HyXe) MRI was recently demonstrated by our collaborative partnership to provide exquisitely sensitive measurements of regional alveolar lung surface area on the few micron scale. By using the xenon chemical shift to distinguish xenon dissolved in tissue from xenon in the gaseous phase, we observed the temporal increase in phase exchange to depend on the square root of the exchange time. The ratio of the dissolved signal to the gas signal is proportional to the parenchyma partition coefficient and the average surface-to-volume ratio. The time to saturation reveals the parenchyma thickness (squared) scaled by the tissue diffusion constant. We propose measurements of lung surface area in smokers correlated with pack-years. In Phase 1 we will measure 20 subjects with smoking histories greater than 20 pack-years and 10 age and gender matched healthy adults. Data will be analyzed to determine average lung surface area correlates in males and females. In Phase 2 we will expand the study statistics to include more smokers, and remeasure the original subjects to determine tissue loss with time in a longitudinal study.