Evaluation of Lymph Flow and Function

描述(申请人提供)：淋巴网络是一种运输系统，专门用于将液体和其他溶解和形成的元素从间质通过结节输送到静脉循环。淋巴管存在于人体的几乎所有部位，在液体和蛋白质的稳态、脂质运输和免疫功能中发挥着重要作用。所有这些都依赖于淋巴流的产生和调节。因此，淋巴流动/功能异常会导致许多病理变化，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了解仍然相当初级，对淋巴参与这些疾病过程的研究还很少，因此对淋巴疾病的有效认识相当罕见。对淋巴功能缺乏了解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上都是一个问题，但在微小的微观淋巴管中原位测量淋巴流量尤其困难，因为淋巴系统的许多功能都是在这里完成的，而且大多数实验研究都是在这里进行的。使这个问题更加复杂的是，淋巴流动依赖于瓣膜和泵(淋巴管的内在和外在的)复杂的、分布的相互作用。我们的总体目标是开发技术，通过量化体内和体外小/微观淋巴管中的实验淋巴流量，实现更好、更快地评估淋巴功能的方法。具体目标是：1.将高速数字视频显微成像与自动相关数字粒子跟踪相结合，实时测量淋巴流速。2.建立更好的淋巴管内流体动力学计算模型，将流体速度、剪切和流动联系起来。我们将把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结合起来，以实现这些目标。

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.