Flow Structure Interaction Model for COPD

COPD 的流结构相互作用模型

• 批准号: 9769317
• 负责人: Anand Prasad Santhanam
• 金额: $ 36.94万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9769317
• 关键词: Algorithms; Behavior; Biological Markers; Biomechanics; Breathing; Bronchodilator Agents; Carbon Dioxide; Cause of Death; Characteristics; Chronic; Chronic Obstructive Airway Disease; Clinical; Clinical Trials; Communities; Coupling; Data; Development; Diagnostic; Disease; Disease Progression; Dose; Elasticity; Enrollment; Ensure; Environmental air flow; Exhibits; Extravasation; Forced expiratory volume function; Formulation; Functional disorder; Future; Gases; Goals; Image; Lead; Liquid substance; Lung; Lung CAT Scan; Lung diseases; Maps; Measurement; Measures; Methods; Modeling; Monitor; Morphologic artifacts; Motion; Nature; Outcome; Oxygen; Patients; Phenotype; Physiology; Process; Property; Protocols documentation; Pulmonary Emphysema; Pulmonary function tests; Quality of life; Radiation; Radiation Oncology; Radiation therapy; Research; Research Personnel; Resolution; Respiration; Respiratory physiology; Scanning; Severity of illness; Sorting - Cell Movement; Staging; Structure; Structure of parenchyma of lung; Symptoms; Techniques; Testing; Tissue imaging; Tissues; United States; Update; Work; X-Ray Computed Tomography; biomechanical model; clinical implementation; clinically relevant; cost; density; disease classification; disease diagnosis; disease phenotype; effective therapy; image registration; imaging biomarker; improved; insight; lung injury; novel; novel marker; open source; persistent symptom; personalized medicine; pilot trial; prospective; recruit; response; tool; treatment planning; treatment response

PROJECT SUMMARY/ABSTRACT Chronic lower respiratory disease, primarily Chronic Obstructive Pulmonary Disease (COPD), was the third leading cause of death in the United States in 2011. COPD is characterized by damaged lung tissues that alter their biomechanical properties and ventilation profiles. Current staging methods using pulmonary function tests are insufficient to determine COPD phenotypes and the subsequent treatments may not be as effective as possible. New markers are needed to better characterize the full clinical spectrum of the disease and to guide the development and assessment of new and more effective therapies. The goal of this proposal is to develop a method for improving COPD phenotype characterization and response monitoring through a novel patient- specific flow structure interaction (FSI) model, generated using data acquired during free breathing. Although biomechanical properties and airflow dynamics of COPD patients are direct indicators of the phenotype, little work has been done to non-invasively measure or model them in a subject-specific manner. In Aim 1, we will develop a novel low dose process for acquiring fast helical free breathing lung CT images and improving the spatial accuracy of deformable image registration, a process that is critical to the subsequent measurement and characterization of biomechanical lung tissue properties. Current methods are unable to distinguish the fine differences in motion between differing lung structures. The proposed approach takes advantage of the quantitative nature of computed tomography, as well as a recently developed fast helical free breathing CT protocol to provide deformable image registration of unparalleled quality and resolution. In Aim 2, we will employ these registrations, along with fundamental biomechanical principles, to measure the hyperelastic properties of the subject's lungs. Hyperelastic property descriptions allow for nonlinear elastic behavior. Previous work has focused on linear elastic modeling. Our hypothesis is that a hyperelastic model will better characterize diseased tissues. In Aim 3, we will employ computational fluid dynamics techniques to characterize the subject's airflow dynamics. They will be combined with the hyperelastic biomechanical properties measured in SA2 to create the FSI model. In Aim 4, we will conduct a pilot clinical trial enrolling radiation therapy patients with and without COPD, where a bronchodilator will be administered between two CT scanning sessions. The subjects will also receive standard pulmonary functional tests. Our hypothesis is that the FSI model will identify COPD patients from normal lung subjects, and characterize COPD phenotypes better than clinical functional tests, opening the way for research into personalized medicine for these patients to improve their clinical outcomes.

项目总结/摘要 慢性下呼吸道疾病，主要是慢性阻塞性肺疾病（COPD），是第三位 2011年美国的主要死因COPD的特征是肺组织受损， 它们的生物力学特性和通气特性。使用肺功能测试的当前分期方法 不足以确定COPD表型，后续治疗可能不如 可能需要新的标志物来更好地描述该疾病的整个临床谱并指导 开发和评估新的和更有效的疗法。该提案的目标是发展 一种通过新型患者改善COPD表型表征和反应监测的方法， 特定的流动结构相互作用（FSI）模型，使用自由呼吸期间获得的数据生成。 尽管COPD患者的生物力学特性和气流动力学是COPD患者的呼吸系统的直接指标， 表型，很少有工作已经做了非侵入性测量或建模，他们在一个特定的方式。 在目标1中，我们将开发一种用于获取快速螺旋自由呼吸肺CT图像的新型低剂量过程， 提高可变形图像配准的空间精度，这是一个对后续成像至关重要的过程。 生物力学肺组织特性的测量和表征。目前的方法无法 区分不同肺结构之间运动的细微差异。拟议的方法需要 计算机断层扫描的定量性质的优势，以及最近开发的快速螺旋免费 呼吸CT协议，提供无与伦比的质量和分辨率的变形图像配准。在目标2中， 我们将使用这些配准，沿着基本的生物力学原理，来测量 受试者肺部的超弹性特性。超弹性属性描述允许非线性弹性 行为以前的工作主要集中在线性弹性模型。我们的假设是一个超弹性模型 将更好地表征患病组织。在目标3中，我们将采用计算流体动力学技术， 表征受试者的气流动力学。它们将与超弹性生物力学相结合 在SA 2中测量的属性来创建FSI模型。在目标4中，我们将进行一项试点临床试验， 有和没有COPD的放射治疗患者，其中支气管扩张剂将在两次给药之间给药 CT扫描。受试者还将接受标准肺功能检查。我们的假设是 FSI模型将从正常肺部受试者中识别COPD患者，并表征COPD表型 比临床功能测试更好，为这些患者的个性化药物研究开辟了道路 来改善他们的临床结果。