Multiscale image-based modeling and simulation of gas flow and particle transport in the human lungs.
Multiscale image-based modeling and simulation of gas flow and particle transport in the human lungs.
复制标题
DOI：
10.1002/wsbm.1234
复制
发表时间：
2013-09
影响因子：
7.9
通讯作者：
Hoffman, Eric A.
中科院分区：
文献类型：
--
作者：
Lin, Ching-Long;Tawhai, Merryn H.;Hoffman, Eric A.
改善对人类肺部结构和功能在个体和亚群中的关系的理解对肺部医学的未来至关重要。基于图像的肺部测量可以提供局部特征的敏感指标，然而，为了更好地预测肺部对疾病、治疗和环境的反应，希望将来自成像的可量化的区域特征与相关的增值高级建模相结合。考虑到这一目标，将回顾计算流体动力学(CFD)在支气管呼吸道研究中的最新进展--从单分支对称模型到基于图像的多尺度特定对象肺模型。CFD模型与局部实质组织扩张的相互作用--通过图像配准进行评估--允许对环境、可吸入气雾剂积累的热点和炎症之间的相互作用有新的理解。为了在CFD中将通风功能与图像衍生的中央气道结构联系起来，将引入一种从模型入口到终末细支气管的气道几何建模方法。最后，讨论了湍流和CFD湍流模型对气溶胶输送和沉积的影响。许多研究小组一直在用CFD模拟人类肺部的气流和颗粒传输，他们的兴趣一直是研究流动物理和呼吸道阻力，改善药物输送，或调查哪些人群最容易受到吸入污染物的影响。在进行呼吸道CFD研究时，需要考虑的三个最重要的因素是肺结构、局部肺功能和流动特性。它们的正确治疗很重要，因为治疗性或污染物颗粒的运输取决于输送它们的气流的特性；而肺部的气流取决于呼吸道的几何形状和通风如何分配到周围组织。人类的呼吸道结构跨越了20多代人，从胸腔外的呼吸道(口腔或鼻腔，并通过咽和喉到达气管)，然后是传导呼吸道、呼吸道和肺泡。个体和亚群(根据性别、年龄、种族和正常与疾病状态)的呼吸道可能表现出不同的尺寸、分支模式和角度，以及厚度和僵硬。在局部水平上，人们希望捕捉详细的流动特征，例如局部速度分布、剪切力和压力，用于预测特定于个体几何形状的气道(肺结构)模型中的颗粒传输，以了解受试者之间的气道几何形状(正常或病理)变化如何影响颗粒的传输和沉积。在系统生物学或多尺度建模方法中，这些局部流动特征可以进一步与用于研究机械转导的上皮细胞模型相结合。在全球(器官)层面上，人们希望匹配特定于个人的区域通风(肺功能)，从而确保输送吸入颗粒物的流动适当地分布在整个肺模型中。没有考虑到通风的真实分布的计算模型不能预测真实的颗粒分布或靶向药物沉积。此外，人体肺中的流动在上呼吸道和近侧气道中可以是过渡性的或湍流的，而在远侧呼吸道中可以变成层流。层流、过渡区和湍流区的流动具有不同的时空尺度。因此，在局部和全局水平上建模气道结构和预测气流和颗粒传输需要图像引导的多尺度建模策略。在本文中，我们将回顾前述关于人类肺部CFD研究的三个关键方面：气道结构(导气管)、肺功能(区域通风和边界条件)和流动特性(湍流的模拟及其对颗粒传输的影响)。对于气道结构的建模，我们将重点关注传导气道，并回顾对称与非对称气道模型、理想化与基于CT的气道模型以及多尺度特定于受试者的气道模型。在CFD中施加特定于受试者的生理边界条件(BCS)对于匹配个体的局部通风是必不可少的，这对于研究吸入性气溶胶在亚群中的优先沉积也是至关重要的，例如正常人和可能表现出不同通风模式的哮喘患者。特定于受试者的区域通风定义了气流在呼吸道段和分叉处的分布和特征，从而决定了气溶胶在整个肺内的传输和沉积。需要湍流模型来捕捉人体肺部气体流动的瞬变和湍流性质。因此，将讨论不同湍流模型的优缺点以及它们对颗粒输运的影响。这项研究的最终目标是在正常和疾病肺部的亚群中识别敏感的结构和功能变量，以用于潜在的临床应用。
Improved understanding of structure and function relationships in the human lungs in individuals and sub-populations is fundamentally important to the future of pulmonary medicine. Image-based measures of the lungs can provide sensitive indicators of localized features, however to provide a better prediction of lung response to disease, treatment and environment, it is desirable to integrate quantifiable regional features from imaging with associated value-added high-level modeling. With this objective in mind, recent advances in computational fluid dynamics (CFD) of the bronchial airways - from a single bifurcation symmetric model to a multiscale image-based subject-specific lung model - will be reviewed. The interaction of CFD models with local parenchymal tissue expansion - assessed by image registration - allows new understanding of the interplay between environment, hot spots where inhaled aerosols could accumulate, and inflammation. To bridge ventilation function with image-derived central airway structure in CFD, an airway geometrical modeling method that spans from the model ‘entrance’ to the terminal bronchioles will be introduced. Finally, the effects of turbulent flows and CFD turbulence models on aerosol transport and deposition will be discussed. CFD simulation of airflow and particle transport in the human lung has been pursued by a number of research groups, whose interest has been in studying flow physics and airways resistance, improving drug delivery, or investigating which populations are most susceptible to inhaled pollutants. The three most important factors that need to be considered in airway CFD studies are lung structure, regional lung function, and flow characteristics. Their correct treatment is important because the transport of therapeutic or pollutant particles is dependent on the characteristics of the flow by which they are transported; and the airflow in the lungs is dependent on the geometry of the airways and how ventilation is distributed to the peripheral tissue. The human airway structure spans more than 20 generations, beginning with the extra-thoracic airways (oral or nasal cavity, and through the pharynx and larynx to the trachea), then the conducting airways, the respiratory airways, and to the alveoli. The airways in individuals and sub-populations (by gender, age, ethnicity, and normal vs. diseased states) may exhibit different dimensions, branching patterns and angles, and thickness and rigidity. At the local level, one would like to capture detailed flow characteristics, e.g. local velocity profiles, shear stress, and pressure, for prediction of particle transport in an airway (lung structure) model that is specific to the geometry of an individual, to understand how inter-subject variation in airway geometry (normal or pathological) influences the transport and deposition of particles. In a systems biology – or multiscale modeling – approach, these local flow characteristics can be further integrated with epithelial cell models for the study of mechanotransduction. At the global (organ) level, one would like to match regional ventilation (lung function) that is specific to the individual, thus ensuring that the flow that transports inhaled particles is appropriately distributed throughout the lung model. Computational models that do not account for realistic distribution of ventilation are not capable of predicting realistic particle distribution or targeted drug deposition. Furthermore, the flow in the human lung can be transitional or turbulent in the upper and proximal airways, and becomes laminar in the distal airways. The flows in the laminar, transitional and turbulent regimes have different temporal and spatial scales. Therefore, modeling airway structure and predicting gas flow and particle transport at both local and global levels require image-guided multiscale modeling strategies. In this article, we will review the aforementioned three key aspects of CFD studies of the human lungs: airway structure (conducting airways), lung function (regional ventilation and boundary conditions), and flow characteristics (modeling of turbulent flow and its effect on particle transport). For modeling airway structure, we will focus on the conducting airways, and review both symmetric vs. asymmetric airway models, idealized vs. CT-based airway models, and multiscale subject-specific airway models. Imposition of physiological subject-specific boundary conditions (BCs) in CFD is essential to match regional ventilation in individuals, which is also critical in studying preferential deposition of inhaled aerosols in sub-populations, e.g. normals vs. asthmatics that may exhibit different ventilation patterns. Subject-specific regional ventilation defines flow distributions and characteristics in airway segments and bifurcations, which subsequently determines the transport and deposition of aerosols in the entire lungs. Turbulence models are needed to capture the transient and turbulent nature of the gas flow in the human lungs. Thus, the advantages and disadvantages of different turbulence models as well as their effects on particle transport will be discussed. The ultimate goal of the development is to identify sensitive structural and functional variables in sub-populations of normal and diseased lungs for potential clinical applications.
登录
查看更多内容
影响因子：
3.8
作者：
Corley, Richard A.;Kabilan, Senthil;Einstein, Daniel R.
通讯作者：
Einstein, Daniel R.
影响因子：
3.8
作者：
Choi, Jiwoong;Xia, Guohua;Tawhai, Merryn H.;Hoffman, Eric A.;Lin, Ching-Long
通讯作者：
Lin, Ching-Long
影响因子：
19.7
作者：
De Backer, Jan W.;Vos, Wim G.;De Backer, Wilfried
通讯作者：
De Backer, Wilfried
DOI：
10.1164/rccm.201107-1317pp
发表时间：
2012-02-15
影响因子：
24.7
作者：
Jarjour, Nizar N.;Erzurum, Serpil C.;Busse, William W.
通讯作者：
Busse, William W.
影响因子：
4.6
作者：
Choi, Jiwoong;Tawhai, Merryn H.;Lin, Ching-Long
通讯作者：
Lin, Ching-Long