Evaluation of Lymph Flow and Function

描述（由申请人提供）：淋巴网络是一个运输系统，专门用于将液体和其他溶解和形成的元素从淋巴结通过淋巴结转移到静脉循环。淋巴管几乎存在于身体的所有部位，并在液体和蛋白质稳态、脂质转运和免疫功能中发挥重要作用。所有这些都依赖于淋巴液流动的产生和调节。正因为如此，异常的淋巴流动/功能导致许多病理学，包括水肿、炎症、转移、肥胖和免疫功能障碍。由于我们对淋巴系统的许多基本功能的理解仍然相当初级，淋巴在这些疾病过程中的参与严重不足，使得淋巴疾病的有效识别非常罕见。导致对淋巴功能认识不足的一个重要因素是缺乏合适的技术来测量淋巴流量。虽然这在淋巴生物学和医学的各个层面都是一个问题，但在完成淋巴系统的许多功能和进行大多数实验研究的小显微镜下原位测量淋巴流量特别困难。使这个问题更加复杂的是，淋巴液流动依赖于阀门和泵的复杂的、分布式的相互作用（对于淋巴系统来说，既有内在的，也有外在的）。我们的总体目标是开发技术，将允许更好，更快的方法来评估淋巴功能，通过量化实验淋巴流量在小/微观淋巴管原位和离体。具体目标是：1.将联合收割机高速数字视频显微镜成像与自动相关数字粒子跟踪相结合，以实时测量淋巴速度。2.开发更好的流体动力学计算模型，以关联流体速度，剪切和流量。我们将联合收割机的淋巴生理学家和生物医学工程师的专业知识与合作的历史，以完成这些目标。

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.