Multi-center Structural & Functional Quantitative CT Pulmonary Phenotyping

描述（由申请人提供）：局部肺功能的生物标志物，加上经验证的评估肺解剖特征的低剂量方法，对于促进COPD和哮喘新干预措施的发现和测试至关重要。这项拟议的生物工程研究伙伴关系旨在利用新兴的多光谱计算机断层扫描（目前为双能CT：DECT）采集技术，仔细评估剂量降低方法，以及统计聚类分析的新方法，以扩展多中心研究中使用的生物标志物，以识别肺部疾病的亚群。目前的CT方法主要集中在实质破坏，空气潴留和气道重塑。我们最近的研究结果发表在《美国国家科学院院刊》和《新英格兰医学杂志》上，越来越多的证据表明肺气肿的病因可能与COPD患者对炎症的异常血管反应有关。为了进一步验证这些发现，我们专注于多光谱CT，以简化目前的动态CT方法在其评估的通气和灌注。使用DECT，我们可以简化为单次氙气呼吸或缓慢外周注射碘化造影剂来评估局部通气或灌注血容量（PBV）。我们的方法包括5个紧密结合的目标，旨在：1）建立在定义COPD和哮喘亚群中实现重要测量所需的最小剂量; 2）使用我们的肺灌注和通气的良好表征的CT评估，使用动态轴向成像来验证DECT的指标，通过单次屏气/单肺容量技术提供通气和灌注指数; 3）将肺的图像分割扩展到肺动脉树和肺静脉树，以进一步将结构链接到功能，以及可靠地提供用于将肺划分为作为标准感兴趣区域的亚叶段的框架;四、测试一种新的聚类分析方法的应用，以便定量CT的测量完全解释疾病亚组的特定表型，并将其与计算流体动力学模型，以便可以更好地理解假定的表型;最后5）提供一个框架，使新开发的协议在制造商和扫描仪模型之间协调一致，允许跨机构数据收集，并提供一种手段，使技术能够在生物学研究的背景下取得进展。 公共卫生相关性： 肺部结构的定量X射线CT已成功地提供了检测早期肺部疾病的客观方法，并将受试者分为亚组，以帮助寻求COPD和哮喘的新疗法。我们现在力求：1）增加基于CT的功能测量，我们相信这将更深入地了解肺部异常的实际原因; 2）降低测量所需的X射线剂量; 3）开发新的方法来利用这些大量信息;以及4）提供跨机构研究的方法，从而可以适应多个制造商的设备以及随着时间的推移适应设备的变化。

DESCRIPTION (provided by applicant): Biomarkers of regional lung function, coupled with validated low dose methods of assessing anatomic features of the lung are critical to promote discovery and testing of new interventions in COPD and asthma. This proposed bioengineering research partnership seeks to take advantage of the emerging acquisition technique of multi-spectral computed tomography (currently dual energy CT: DECT), careful evaluation of dose lowering methods, and novel approaches to statistical cluster anlaysis to expand the biomarkers used in multi-center studies to identify sub-populations of lung disease. Current CT methods have focused largely on parenchymal destruction, air trapping and airway remodeling. With our recent findings reported in the Proceedings of the National Acedemy of Sciences and the New England Journal of Medicine, there is growing evidence that the etiology of emphysema may be correlated with abnormal vascular responses to inflammation in COPD. To further validate these findings, we focus on multi-spectral CT to simplify the current dynamic CT approach in its assessment of ventilation and perfusion. With DECT we can simplify to a single breath of xenon gas or a slow peripheral injection of iodinated contrast agent to assess regional ventilation or perfused blood volume (PBV). Our approach consists of 5 tightly integrated aims seeking to: 1) establish the minimum dose required to achieve the measurements of importance in defining COPD and asthma sub-populations; 2) use our well characterized CT assessment of pulmonary perfusion and ventilation using dynamic axial imaging to validate metrics from DECT, providing indices of ventilation and perfusion via single breath hold / single lung volume techniques; 3) expand image segmentation of the lung to the pulmonary arterial and venous trees to further link structure to function as well as to reliabily provide a framework for dividing the lung into sublobar segments as the standard region of interest; 4) test the application of a novel statistica approach to cluster analysis such that the measures from quantitative CT fully account for specific phenotypes for disease subgroups and link to a computational fluid dynamics model such that a putative phenotype can be better understood; and finally 5) provide a framework whereby newly developed protocols are harmonized across manufacturers and scanner models, allowing for cross institutional data collection and a means whereby technology is allowed to progress within the context of longitudial studies. PUBLIC HEALTH RELEVANCE: Quantitative x-ray CT of lung structure has been successful in providing objective methods for detecting early lung disease and dividing subjects into sub-groups to aid in seeking new therapies for COPD and asthma. We now seek to: 1) add CT-based measures of function which we believe will provide greater insight into the actual cause of the lung abnormality; 2) lower x-ray dose needed for the measures; 3) develop new methods to make use of these large amounts of information; and 4) provide ways whereby cross institutional studies can accommodate multiple manufacturer's equipment as well as accommodate changes in equipment over time.