MSM Multiscale Human Respiratory System Simulations to Study Health Effects

描述(由申请人提供)：提出了一种多尺度策略，以开发、耦合、应用和验证人体呼吸中可分辨和亚分辨尺度的多模式成像和物理建模。高分辨率计算机断层扫描(HRCT)将被用来描述肺的“大尺度”对流范围。显微计算机断层摄影术(.CT)和共聚焦显微镜(CLSM)将被用来表征呼吸单元的“微尺度”全球和细胞结构。多相计算流体力学和准一维泛函模型将分别在宏观和微观尺度上模拟多组分流体力学。将开发软件基础设施和两相流体力学模型，以解决这两个尺度上的物理耦合问题。模型预测将根据文献中的实验和临床数据进行验证。拟议研究的一个新颖和关键要素是，将利用核反应堆安全/模拟界最近制定的降维耦合战略和航空航天科学界制定的多学科数据交换标准，开发功能生物学尺度之间的接口。将开发宏观和微观尺度之间以及成像和物理模拟之间的耦合技术；这些将产生一个系统级模型，该模型适应对流呼吸物理与摄取、沉积和疾病状态形态之间的关键双向耦合。这种综合的方法将阐明迄今为止无法获得的物理理解、依赖性和治疗含义。将要开发的耦合软件将是模块化和开源的，这样其他研究人员就可以在宏观和微观尺度上“插入”他们的模型，和/或将系统进化到其他器官或人类系统，如肝脏或肾脏。这项研究的最终公共卫生目标是增进对呼吸功能和疾病的了解，以及评估治疗、损伤、手术干预和衰老对肺结构和功能的影响。多个尺度之间的基于物理的耦合是迈向完整的人类呼吸系统综合生理模型的关键一步：“虚拟人类肺”。

DESCRIPTION (provided by applicant): A multi-scale strategy is proposed to develop, couple, apply, and validate multimodality imaging and physics modeling of resolvable and sub-resolvable scales in human respiration. High-resolution computed tomography (HRCT) will be used to characterize the "macroscale" convective range of the lung. Microscopic computed tomography (.CT), and confocal microscopy (CLSM), will be used to characterize the "microscale" global and cellular architectures of the respiratory units. Multiphase computational fluid dynamics and quasi-one-dimensional functional modeling will be used to simulate the multi-component fluid mechanics at the macro- and micro-scales, respectively. Software infrastructure and two-phase fluid mechanics models will be developed to address the coupling between the physics at these two scales. Model predictions will be validated against experimental and clinical data from the literature. A novel and critical element of the proposed research is that the interfaces between functional biological scales will be developed using recent dimension-reducing coupling strategies developed in the nuclear reactor safety/simulation community, and multidisciplinary data-exchange standards developed in the aerospace sciences community. Coupling technologies will be developed between macro- and microscales, and between imaging and physical modeling; these will yield a system-level model that accommodates the critical two-way coupling between convective respiration physics and uptake, deposition, and disease-state morphology. Such an integrated approach will elucidate heretofore inaccessible physical understanding, dependencies, and treatment implications. The coupling software to be developed will be modular and open-source so other investigators can "plug-in" their models at the macro- and micro-scales, and/or evolve the system to other organs or human systems such as the liver or kidney. The ultimate public health goal of the research is improved understanding of respiratory function and disease, and evaluation/assessments of the effects of therapies, injury, surgical intervention, and aging on lung structure and function. The physics-based coupling between multiple scales is a critical step towards a complete integrated physiological model of the human respiratory system: a "virtual human lung."