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，结合经验证的低剂量肺解剖特征评估方法，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采集技术（目前为双能CT: DECT），仔细评估降低剂量的方法，以及统计聚类分析的新方法，以扩大在多中心研究中使用的生物标志物，以确定肺部疾病的亚群。目前的CT方法主要集中在实质破坏，空气捕获和气道重塑。我们最近在《美国国家科学院院刊》和《新英格兰医学杂志》上发表的研究结果表明，越来越多的证据表明，肺气肿的病因可能与慢性阻塞性肺病患者血管对炎症的异常反应有关。为了进一步验证这些发现，我们将重点放在多光谱CT上，以简化目前动态CT评估通气和灌注的方法。使用DECT，我们可以简化为单次呼吸氙气或缓慢的周围注射碘造影剂来评估区域通气或灌注血容量（PBV）。我们的方法由5个紧密结合的目标组成，旨在：1)建立所需的最小剂量，以实现对定义COPD和哮喘亚群具有重要意义的测量；2)利用动态轴向成像对肺灌注和通气进行特征化的CT评估，验证DECT的指标，通过单次屏气/单肺容积技术提供通气和灌注指标；3)将肺的图像分割扩展到肺动脉和静脉树，进一步将结构与功能联系起来，并为将肺划分为叶下段作为标准感兴趣区域提供可靠的框架；4)测试一种新的统计方法在聚类分析中的应用，使得来自定量CT的测量能够充分解释疾病亚组的特定表型，并与计算流体动力学模型相关联，从而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型号之间协调一致，允许跨机构数据收集，并提供一种在纵向研究背景下允许技术进步的手段。

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.