Automated analysis of NKT cell sentry pattern in liver with metastatic tumor

描述（由申请人提供）：最近的研究已经确定了表达T细胞受体（NKT细胞）的自然杀伤细胞亚群。这些细胞被认为在肝脏中具有哨兵功能，可能参与早期发现和消除转移到肝脏的肿瘤细胞。然而，人们对这种哨兵功能的本质知之甚少。阐明NKT细胞在肝脏中的哨兵功能的一个主要障碍是缺乏适当的方法来量化NKT细胞在肝窦中的迁移行为。先前的研究已经提出，在没有检测目标的情况下，NKT细胞通过正弦波的运动基本上是随机的。我们假设，肝脏中肿瘤细胞的存在导致NKT细胞的运动模式逐渐变得不那么随机，而更有方向性，这是与肿瘤细胞接近的功能。为了验证这一假设，我们提出了三个目标：1)开发一种方法，可以自动检测和跟踪肝小叶内的肝脏NKT细胞和肿瘤。2)开发一种方法，允许自动表征NKT细胞与肿瘤相关的运动行为，包括外渗。3)基于大量NKT细胞的运动行为数据，检验NKT细胞的运动行为与肿瘤之间关系的假设。为了实现这些目标，我们已经建立了肝脏体内成像专家和图像分析和计算方法专家之间的合作。该项目的成功完成将为分析这些免疫细胞在体内的哨兵行为提供一种新的方法，并阐明NKT细胞在体内定位肝脏肿瘤细胞的机制。

DESCRIPTION (provided by applicant): Recent studies have identified a subset of natural killer cells that express T cell receptors (NKT cells). These cells have been proposed to serve a sentry function in the liver and are likely to be involved in early detection and elimination of tumor cells metastasizing to the liver. However, the nature of this sentry function is poorly understood. A major obstacle to elucidation of the sentry function of NKT cells in the liver is the lack of appropriate methodology for quantifying the migratory behavior of the NKT cells in the hepatic sinusoids. Previous studies have proposed that the movement of NKT cells through the sinusoids is essentially random in the absence of a target for detection. We hypothesize that the presence of tumor cells in the liver causes the NKT cell motion patterns to become progressively less random and more directed as a function of proximity to the tumor cell. In order to test this hypothesis, we propose three aims: 1) Develop a methodology that will allow automatic detection and tracking of liver NKT cells and tumor within the hepatic lobule in vivo. 2) Develop a methodology that will allow automatic characterization of the NKT cell's motion behavior with respect to tumor including extravasation. 3) Test the hypotheses of the relationship between the NKT cell's motion behavior and tumor based on a large amount of motion behavior data of NKT cell. In order to accomplish these aims, we have established a collaboration between an expert in in vivo imaging of the liver and an expert in image analysis and computational methods. Successful completion of this project would provide a novel approach to the analysis of sentry behavior of these immune cells in vivo as well as elucidate the mechanisms by which NKT cells locate tumor cells in the liver in vivo.