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.

该项目的目标是开发方法来标记特定的 具有 MRI 可检测造影剂的细胞类型并追踪 通过 MRI 无创地观察这些标记细胞在活体动物体内的运动 技术。 该想法目前应用于急性疾病的早期检测 器官移植中的器官排斥反应。 众所周知， T细胞是急性移植排斥反应的主要效应细胞。 我们希望 通过 MRI 追踪 T 细胞“归巢”至移植部位 通过用 MR 可检测造影剂标记 T 细胞来抑制排斥反应。 葡聚糖包覆的超顺磁性氧化铁（SPIO）颗粒 用作 MR 造影剂，但目前尚未商业化 可用的。 我们合成了自己的葡聚糖包被的 SPIO 颗粒， 称为 Ferumag，具有可比的特性 到以前获得的商业样品。 T 细胞被标记为 Ferumag 颗粒通过内吞作用产生标记效率 约20%。 对内吞条件的一些修改 为提高标注效率而进行。 为了进一步 提高检测器官排斥反应的灵敏度，我们正在 目前正在探索培养 T 细胞的可能性 特定于捐赠者，以便他们有选择地居住在 拒绝站点。 追踪细胞迁移的一个主要困难是 由于人口稀少，MRI 的敏感性较低 标记的 T 细胞导致内标记细胞浓度低 图像体素。 然而，提高图像分辨率应该会导致 体素内标记细胞浓度较高，其中包含 标记细胞，从而增强图像对比度。 我们调查过 这一假设是通过 Ferumag 标记的 T 细胞的高分辨率 MRI 得出的 Ferumag 标记的单细胞位置的样本 已通过 MRI 成像。 用 Dil 共标记 T 细胞以获取荧光 显微镜研究提供了标记 T 细胞位置的验证 样品。