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

肝脏转移性肿瘤中 NKT 细胞哨兵模式的自动分析

• 批准号: 7197547
• 负责人: MARK G CLEMENS
• 金额: $ 21.54万
• 依托单位: UNIVERSITY OF NORTH CAROLINA CHARLOTTE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7197547
• 关键词: Acceleration; Architecture; Behavior; Biology; CXCR6 gene; Cells; Collaborations; Computer Analysis; Computing Methodologies; Data; Data Set; Detection; Discontinuous Capillary; Disease; Early Diagnosis; Effectiveness; Entropy; Exclusion; Exhibits; Extravasation; Feedback; Generic Drugs; Hepatic lobule; Host Defense; Image Analysis; Immune; Latex Bead; Liver; Lobular; Mediator of activation protein; Medical Surveillance; Methodology; Microcirculation; Modeling; Motion; Movement; Natural Killer Cells; Nature; Neoplasm Metastasis; Output; Pattern; Probability; Rate; Sampling; Snakes; T-Cell Receptor; T-Lymphocyte; Testing; Time; Variant; Virus Diseases; base; chemokine receptor; computer science; design; hepatic sinusoid; in vivo; killer T cell; killings; liver imaging; migration; neoplastic cell; novel strategies; particle; prevent; research study; response; tool; tumor

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.

描述（由申请人提供）：最近的研究确定了表达T细胞受体（NKT细胞）的天然杀伤细胞的子集。这些细胞已被提议在肝脏中发挥哨兵功能，并可能参与早期检测和消除肿瘤细胞向肝脏转移的肿瘤细胞。但是，这种哨兵功能的性质知之甚少。 NKT细胞在肝脏中阐明NKT细胞哨兵功能的主要障碍是缺乏量化肝弦正弦波中NKT细胞迁移行为的适当方法。先前的研究表明，在没有检测靶点的情况下，NKT细胞通过正弦体的运动本质上是随机的。我们假设肝脏中肿瘤细胞的存在会导致NKT细胞运动模式逐渐变得越来越少，并且随着肿瘤细胞的邻近性而越来越定向。为了检验这一假设，我们提出了三个目的：1）开发一种方法，该方法将允许自动检测和跟踪体内肝小叶中的肝脏NKT细胞和肿瘤。 2）开发一种方法，该方法将可以自动表征NKT细胞在肿瘤（包括渗出）方面的运动行为。 3）测试基于NKT细胞的大量运动行为数据，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，我们建立了肝脏体内成像专家与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体内这些免疫细胞的哨兵行为提供一种新颖的方法，并阐明了NKT细胞在体内肝脏在肝脏中定位肿瘤细胞的机制。