Modelling lung deposition of inhaled particles in cystic fibrosis

该项目将使用数学和计算模型来研究肺部呼吸道流动和传输的基本物理机制，特别是考虑与囊性纤维化相关的特征和药物输送的相关方面。呼吸道中存在大量高粘性粘液是囊性纤维化的主要症状，这使得有效地将治疗吸入到肺部深处具有挑战性。利用理论连续介质力学的机制，这个项目将寻求提高我们对粘液如何在肺部分布和运输，以及这如何影响不同给药方法的疗效的理解。最初的重点将是疾病粘液的复杂流变性(如其屈服应力)对肺外围小气道内传输的影响，这些小气道是肺部的一些区域，很难通过实验研究，也很难使用医学成像来解决。在该项目的后期阶段，将使用多尺度模拟方法，利用离散微积分的工具，评估小气道运输过程如何影响器官尺度上的药物输送，从而纳入整个呼吸道树的通风影响。这将需要求解大规模离散网络上的输运方程，由于涉及大量的通道，这将需要相对密集的计算。这种方法与降维技术相结合，可以研究呼吸道几何形状对肺部运输和疾病发展的影响。在整个项目中，模型的开发将受到生理和临床应用的推动，特别是将吸入雾化药物有效地输送到囊性纤维化中受损或阻塞的肺部区域。为了实现这一目标，学生将由一个由多学科导师组成的团队进行指导，该团队来自曼彻斯特大学数学系和感染、免疫和呼吸医学部。该项目产生的模型可能在囊性纤维化(例如，基础流体力学)之外具有更广泛的潜在应用，但这种针对疾病的方法意味着该项目将提供新的能力，以实际测试和优化硅胶中的药物输送方案，从而真正改变患者的治疗。

This project will use mathematical and computational modelling to investigate fundamental physical mechanisms of flow and transport in lung airways, considering in particular features relevant to cystic fibrosis and related aspects of drug delivery. The presence of large quantities of highly viscous mucus in airways is a primary symptom of cystic fibrosis, making it challenging to effectively administer inhaled therapies deep into the lungs. Using the machinery of theoretical continuum mechanics, this project will seek to improve our understanding of how mucus is distributed and transported throughout the lungs, and how this could affect the efficacy of different methods of drug delivery. There will be an initial focus on the impact of the complex rheological properties of diseased mucus (such as its yield stress) on transport within small airways in the lung periphery, regions of the lungs that are difficult to study experimentally and difficult to resolve using medical imaging. In the later stages of the project, multi-scale modelling approaches exploiting tools from discrete calculus will be used to assess how small-airway transport processes impact on drug-delivery at the organ scale, allowing incorporation of the effects of ventilation in the whole airway tree. This will require solution of transport equations on massive discrete networks, which will require relatively intensive computation due to the large number of airways involved. This approach, combined with dimensionality reduction techniques, will allow investigation into the effects of airway geometry on transport in the lungs and on development of disease. Throughout the project, model development will be motivated by the physiological and clinical applications, in particular the effective delivery of inhaled aerosolised pharmaceuticals to damaged or blocked lung regions in cystic fibrosis. To achieve this, the student will be guided by a multidisciplinary team of supervisors, drawn from the Department of Mathematics and the Division of Infection, Immunity & Respiratory Medicine at the University of Manchester. The models emerging from the project are likely to have broader potential application beyond cystic fibrosis (for example, to fundamental fluid mechanics), but this disease-specific approach means that the project will give new capabilities to realistically test and optimise drug-delivery protocols in silico that can make a real difference to patient treatment.