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，用于开发、耦合、应用和验证人体呼吸中可分辨和亚可分辨尺度的多模态成像和物理建模。高分辨率计算机断层扫描（HRCT）将用于表征肺的“宏观”对流范围。显微计算机断层扫描(。CT)和共聚焦显微镜（CLSM）将用于表征呼吸单位的“微尺度”整体和细胞结构。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来解决这两个尺度上物理之间的耦合。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因素是，功能生物尺度之间的接口将使用核反应堆安全/模拟社区开发的最新降维耦合策略和航空航天科学界开发的多学科数据交换标准来开发。发展宏观与微观、成像与物理建模之间的耦合技术；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难以理解的物理理解、依赖关系和治疗含义。将要开发的耦合软件将是模块化和开源的，因此其他研究人员可以在宏观和微观尺度上“插入”他们的模型，并/或将该系统进化到其他器官或人体系统，如肝脏或肾脏。这项研究的最终公共卫生目标是提高对呼吸功能和疾病的理解，以及对治疗、损伤、手术干预和衰老对肺结构和功能的影响的评估。多个尺度之间基于物理的耦合是迈向人类呼吸系统完整集成生理模型的关键一步：“虚拟人体肺”。

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."