Evaluation of Lymph Flow and Function

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DESCRIPTION (provided by applicant): The lymphatic network is a transport system, specialized for moving fluid and other dissolved and formed elements from the interstitium through the nodes to the venous circulation. Lymphatics are found in nearly all parts of the body and play important roles in fluid and protein homeostasis, lipid transport and immune function. All of these rely on the generation and regulation of lymph flow. Because of this, abnormal lymph flow/function contributes to a number of pathologies including edema, inflammation, metastasis, obesity, and immune dysfunction. Because our understanding of many basic functions of the lymphatic system is still quite rudimentary, lymphatic involvement in these disease processes is grossly understudied making the recognition of lymphatic diseases effectively quite rare. An important factor contributing to the poor understanding of lymphatic function is the lack of suitable techniques to measure lymph flow. While this is a problem at all levels of lymphatic biology and medicine, it is particularly difficult to measure lymph flow in situ in the small microscopic lymphatics where many of the functions of the lymphatic system are accomplished and most experimental studies are conducted. Compounding this problem is the fact that lymph flow relies on a complex, distributed interaction of valves and pumps (both intrinsic and extrinsic to the lymphatics.) Our general goal is to develop techniques that will allow better, faster methods of evaluating lymphatic function by quantifying experimental lymph flow in the small/microscopic lymphatics in situ and ex vivo. The specific aims are: 1. Combine hi-speed digital videomicroscopic imaging with automated correlative digital particle tracking to measure lymph velocity in real-time. 2. Develop better computational models of the fluid dynamics inside lymphatics to correlate fluid velocity, shear and flow. We will combine the expertise of lymphatic physiologists and biomedical engineers with a history of working together to complete these aims.