Mass Transfer Phenomena in the Lymphatic System

该研究项目的主要目的是在一定范围的舒张期直径和跨壁压力的多个尺度上量化淋巴肌肉细胞(LMC)的收缩能力。这一目标的动机是在淋巴推进中收缩力量的重要性以及淋巴瓣膜功能所需的压差的产生。从这项研究中获得的知识将被纳入基于集中参数和计算质量传输方法的淋巴系统流动的多尺度模型中。这将使用实验和计算方法来完成，主要实验由合作者执行，然后作为研究项目的一部分开发理论模型。将进行实验以获得确定作为上游和下游压力的函数的收缩力所需的数据。将进行两个系列的实验，第一个系列包括插入淋巴管、改变压力和测量血管内径和外径。第二个系列的实验将使用钢丝肌图仪来确定分离淋巴管的长度-张力关系。这个项目将使用处理实验结果所需的计算方法，因为LMC的收缩能力只能间接测量。根据实验结果确定伸缩性的基础是平衡周向力。几何数据和第一系列实验中淋巴管内压力的测量将结合在一起来计算收缩力。对第二系列实验的分析将根据力传感器和平均壁厚的测量来计算收缩张力，并将结果与五个或更多淋巴管的有限元模型进行比较。需要在现有的平滑肌细胞模型的基础上进行进一步的建模，以便将收缩能力纳入淋巴流动模型中。这项研究将是原创性的，因为目前还没有一个单一的平滑肌模型可以应用于所有系统，而且淋巴管中的平滑肌与一直是研究重点的系统中的平滑肌有显着不同。因此，这项研究将是第一个在生理范围内对LMCs的收缩能力进行量化和建模的研究。该项目还将参与研究组的其他研究目标，即表征淋巴瓣的阻力和滞后，以及开发淋巴结内液体流动和白细胞行为的模型。这些目标的结果也将被纳入淋巴系统运输现象的多尺度模型中。淋巴瓣膜的特性将涉及瓣膜的实验特性和所涉及的固体和流体力学的计算模型，这些最终将被结合在一个流体-结构相互作用模型中。对淋巴结进行建模将涉及淋巴流经该节点的计算流体动力学，以及对淋巴结中细胞的基于代理的建模。计算流体力学和基于代理的模型最终将结合在一起，以提供更全面的淋巴结模型。

The primary aim of this research project is to quantify the contractility of lymphatic muscle cells (LMCs) across multiple scales for a range of diastolic diameters and transmural pressures. This aim is motivated by the importance of contractile force in lymph propulsion and the generation of pressure differences required for the function of lymphatic valves. The knowledge gained from this research will be incorporated into multi-scale models of flow in the lymphatic system, which are based on lumped parameter and computational mass transport approaches. This is to be done using both experimental and computational methods, with the main experiments being performed by collaborators and theoretical models then being developed as part of the research project. The experiments will be performed to obtain data required for determining contractile force as a function of the upstream and downstream pressures. Two series of experiments will be performed, the first series will consist of cannulating lymphatic vessels, varying the pressure and measuring both the internal and external vessel diameters. The second series of experiments will use a wire myograph to determine the length-tension relationship of isolated lymphatic vessels. This project will then use computational methods required to process the experimental results because the contractility of the LMCs can only be measured indirectly. The determination of contractility from experimental results is to be based on balancing the circumferential forces. Geometrical data and measurements of the pressure within the lymphangion from the first series of experiments will be combined for the calculation of contractile force. Analysis of the second series of experiments will calculate the contractile tension from measurements of the force transducer and average wall thickness, and the results will be compared with a finite element model of five or more lymphangions. Further modelling based on current models of smooth muscle cells will be required for incorporation of the contractility into the lymphatic flow models. This research will be original as there is currently no single model of smooth muscle that can be applied to all systems and the smooth muscle in lymphatics is significantly different from that in the systems which have been the focus of research. This research will therefore be the first to quantify and model the contractility of LMCs over the physiologic range.The project will also include involvement in the other research aims of the research group, which are to characterize the resistance and hysteresis of lymphatic valves, and to develop models of fluid flow and leukocyte behaviour in lymph nodes. The results from these aims will also be incorporated into multi-scale models of the transport phenomena of the lymphatic system. Characterization of the lymphatic valves will involve experimental characterization of valves and computational models of the solid and fluid mechanics involved, which will ultimately be combined in a fluid-structure interaction model. Modelling the lymph nodes will involve computational fluid dynamics of lymph flow through the node, and agent-based modelling of the cells in lymph nodes. The computational fluid dynamics and agent-based models will ultimately be coupled to provide a more comprehensive model of lymph nodes.