CHAOTIC MIXING OF AEROSOL IN RHYTHMICALLY EXPANDING LUNG

描述（改编自申请人摘要）：本研究的目标 是为了阐明气溶胶沉积的基本机制， 肺腺泡，因为这方面的知识是必不可少的了解的作用， 呼吸道疾病中的细颗粒。目前的理论描述气溶胶 在可逆性腺泡流动的背景下，行为作为分散过程，但 实验观察表明，气溶胶在腺泡中的行为， 不遵循这些理论所预测的基本规则。因此，气溶胶 沉积过程中的腺泡需要重新解释新的理论 场.最近，在离体大鼠肺的流动可视化研究中，直接 已经获得了实验证据， 不可逆的，表现出复杂和回旋的拉伸和折叠流动模式。 基于这些发现，假设肺中的气溶胶行为 外围由拉伸和折叠运动学控制，而不是分散的 流程.为了验证这一假设，提出了三项研究。(1)机制 由于拉伸和折叠运动学， 深入调查。使用最先进的数值技术， 腺泡血流的不可逆性与多鞍区的存在有关 点（存在于每个扩张的肺泡中），以及气溶胶上的异步流动 将研究沉积。(2)这些个体的累积效应 肺泡流现象对全球流动和气溶胶行为将是 研究了(3)从这些理论中产生的综合理论框架 研究（1和2）将针对动物实验进行测试。流动显示 将在离体兔肺上进行气溶胶暴露实验 在相同的条件下，将拉伸和折叠流动模式与 气溶胶沉积模式和团块行为。这些研究将提供一个 为理解气溶胶的机制奠定了坚实的新基础 运输和沉积在肺外周，从而揭示了一个 颗粒物诱导的呼吸道疾病发病机制的重要一步。

DESCRIPTION (Adapted from the applicant's abstract):The goal of this research is to elucidate the underlying mechanisms of aerosol deposition in the pulmonary acinus, as this knowledge is essential to understanding the role of fine particles in respiratory illnesses. Current theories describe aerosol behavior as a dispersive process in the context of reversible acinar flow, but experimental observations show that the behavior of aerosols in the acinus does not follow the basic rules predicted by these theories. Thus, the aerosol deposition process in the acinus needs to be reinterpreted on new theoretical grounds. Recently, with flow visualization studies in excised rat lungs, direct experimental evidence has been obtained that acinar flow can be highly irreversible, exhibiting complex and convoluted stretch-and-fold flow patterns. Based on these findings, it is hypothesized that aerosol behavior in the lung periphery is governed by stretch-and-fold kinematics, rather than dispersive processes. To test this hypothesis, three studies are proposed. (1) Mechanisms governing particle deposition due to stretch-and-fold kinematics will be investigated in depth. Using state of the art numerical techniques, the effects of acinar flow irreversibility associated with the presence of multiple saddle points (present in each expanding alveolus), and asynchronous flow on aerosol deposition will be studied. (2) The cumulative effects of these individual alveolar flow phenomena on the global flow and aerosol behavior will be studied. (3) The comprehensive theoretical framework emerging from these studies (1 and 2) will be tested against animal experiments. Flow visualization and aerosol exposure experiments will be performed on excised rabbit lungs under identical conditions to correlate stretch-and-fold flow patterns with patterns of aerosol deposition and bolus behavior. These studies will provide a solid new foundation to understanding the mechanisms involved in aerosol transport and deposition in the lung periphery, thus shedding light on an important step in the pathogenesis of particle-induced respiratory diseases.