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。将使用显微计算机断层扫描（.CT）和共聚焦显微镜（CLSM）来表征呼吸单位的“微尺度”全局和细胞架构。多相计算流体动力学和准一维函数模型将分别用于模拟宏观和微观尺度的多组分流体力学。将开发软件基础设施和两相流体力学模型，以解决这两个尺度的物理之间的耦合。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且关键的要素是，功能生物尺度之间的接口将使用核反应堆安全/模拟界最近开发的降维耦合策略以及航空航天科学界开发的多学科数据交换标准来开发。耦合技术将在宏观尺度和微观尺度之间以及成像和物理建模之间开发;这些将产生一个系统级模型，该模型可容纳对流呼吸物理学与摄取，沉积和疾病状态形态之间的关键双向耦合。这样一种综合的方法将阐明迄今为止无法理解的物理理解，依赖性和治疗的影响。将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，和/或将系统发展到其他器官或人类系统，如肝脏或肾脏。该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，并评估/评估治疗，损伤，手术干预和老化对肺结构和功能的影响。多尺度之间基于物理的耦合是实现人体呼吸系统完整集成生理模型的关键一步：“虚拟人肺”。"

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."