NON INVASIVE DETECTION OF ORGAN REJECTION BY MRI

通过 MRI 无创检测器官排斥

• 批准号: 6669258
• 负责人: CHIEN HO
• 金额: $ 13.47万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2003-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6669258
• 关键词: Mammalia; animal tissue; bioimaging /biomedical imaging; biomedical resource; immunology; inflammation; lymphatic system; magnetic resonance imaging; technology /technique; transplantation

The goal of this project is to develop methods to label a specific type of cells with MRI detectable contrast agents and to track the movement of these labeled cells non-invasively in live animals by MRI techniques. The idea is currently applied to early detection of acute organ rejection in organ transplantation. It is well known that the T-ceII is the primary effector cell in acute graft rejection. We hope to track by MRI, the "homing" of T-cells to the site of graft rejection by labeling T-cells with MR detectable contrast agents. Dextran-coated superparamagnetic iron-oxide (SPIO) particles have been used as MR contrast agents, but they are currently commercially not available. We have synthesized our own dextran-coated SPIO particles, referred to as Ferumag, which have characteristics that are comparable to previously obtained commercial samples. T-Cells are labeled with Ferumag particles by endocytosis, resulting in a labeling efficiency of about 20%. Several modifications to the endocytosis conditions were carried out to improve the labeling efficiency. To further improve the sensitivity for detecting organ rejection, we are currently exploring the possibility of culturing T-cells that are specific to the donor so that they will selectively home to the rejection site. A major difficulty with tracking cell migration with MRI has been the low sensitivity because of the sparse population of labeled T-cells leading to a low concentration of labeled cells within an image voxel. Increasing image resolution, however, should lead to a higher labeled cell concentration within the voxels that contain labeled cells, thereby enhancing image contrast. We have investigated this hypothesis with high-resolution MRI of Ferumag labeled T-cell samples where the locations of single cells labeled by Ferumag have been imaged by MRI. Co-labeling of T-cells with Dil for fluorescence microscopy studies provide verification of labeled T-ceIl locations in the sample.

该项目的目的是开发标记特定的方法 具有可检测到的对比度的MRI的细胞类型，并跟踪 这些标记的细胞在MRI中非侵入性的细胞运动 技术。 该想法目前适用于急性的早期检测 器官移植中的器官排斥。 众所周知， T-CEII是急性移植排斥的主要效应细胞。 我们希望 通过MRI跟踪，T细胞的“归巢”到移植物位置 通过将T细胞标记为MR可检测的对比剂来排斥。 葡萄糖涂层的超副磁铁氧化物（SPIO）颗粒已经是 用作MR对比代理，但目前不在商业上 可用的。 我们已经合成了自己的葡萄糖涂层的SPIO颗粒， 称为ferumag，具有可比性的特征 以前获得的商业样品。 T细胞标记 通过内吞作用的小颗粒颗粒，导致标记效率 约20％。 内吞作用条件的几种修饰 进行以提高标签效率。 进一步 提高检测器官排斥的灵敏度，我们是 目前正在探索培养T细胞的可能性 特定于捐赠者，以便他们将有选择地回家 拒绝网站。 跟踪细胞迁移的主要困难 MRI一直是低灵敏度，因为人口稀疏 标记的T细胞导致低浓度的标记细胞内 图像体素。 但是，增加图像分辨率应导致 含有较高标记的细胞浓度，其中包含 标记的细胞，从而增强图像对比度。 我们已经调查了 该假设具有标记为T细胞的Ferumag高分辨率MRI 样品中，由Ferumag标记的单细胞的位置具有 由MRI成像。 T-Cell与DIL共同标记以荧光 显微镜研究提供了对标记的T-Ceil位置的验证 样本。