Lymphatic drainage plays a crucial role in the functioning of the immune system, lymphogenic cancer cell metastasis and the pathological accumulation of fluid in the interstitial space, known as edema. This very diverse role finds its origin in the multi-purpose functioning of the lymphatic system alongside the arterio-venous system (see figure whic displays the lymphatic system in the arm and thorax of a woman):
(i) Regulation of immune responses by providing the routes for antigen and immune cell trafficking
(ii) Removal of excess fluid and waste products in the interstitial spaces between cells after nourishing products have been delivered via leakage from the vascular system
(iii) Absorption of fats and vitamins from the digestive system
(iv) Delivery of nutrients to the appropriate cells.
The overall objective of this master thesis project is to gain fundamental insight into the determinants of mass transport in the interstitial tissue space and the lymphatic micro- and macro-circulation via mathematical modelling, in-vivo and ex-vivo experiments in rodents, and 3D reconstruction of the lymphatic vessels from CT images. Throughout the project, we will particularly focus on the lymphatic circulation in the rat forelimb as a small animal model of the human arm, and this for two important reasons:
- Arm edema is still a common co-morbidity in 25% of all women undergoing breast cancer resection surgery (most common cancer in women). Unfortunately, no effective therapy exists. A better understanding of the lymphatic mass transport in the arm might open the way to new and more effective treatments.
- Cancer treatment via targeted drug delivery of nanoparticle-loaded microbubbles is one of the key research lines of the Faculty of Pharmaceutical Sciences at Ghent University. Determining factors for successful in-vivo application are the efficient delivery of microbubbles to the lymphatic nodes via subcutaneous injection (in the arm), and the efficient uptake of released substances by the target cells (dendritic cells). A thorough understanding of lymphatic transport processes would allow for assessing the efficiency of the delivery process and its optimization.