NON INVASIVE DETECTION OF ORGAN REJECTION BY MRI

这个项目的目标是开发方法来标记特定的 使用MRI可检测造影剂的细胞类型并跟踪 磁共振成像研究标记细胞在活体动物体内的非侵入性运动 技巧。这一想法目前被应用于急性胰腺炎的早期检测 器官移植中的器官排斥反应。众所周知， T细胞II是移植物急性排斥反应的主要效应细胞。我们希望 用核磁共振追踪T细胞“归巢”到移植物部位 用MR可检测造影剂标记T细胞的排斥反应。 葡聚糖包覆的超顺磁性氧化铁(SPIO)颗粒已被 用作磁共振造影剂，但目前还没有商业化 可用。我们已经合成了我们自己的葡聚糖包覆的SPIO颗粒， 被称为费鲁马格，它们具有可比的特征 与之前获得的商业样本进行比较。T细胞被标记为 通过内吞作用产生费鲁马格颗粒，从而产生标记效率 大约20%。对内吞条件的几点修改 以提高标记效率。为了进一步 提高检测器官排斥反应的灵敏度，我们正在 正在探索培养T细胞的可能性 特定于捐赠者，这样他们就会有选择地回到 拒绝站点。跟踪细胞迁移的一个主要困难是 由于稀疏的人群，MRI一直是低敏感性的 标记的T细胞导致体内标记细胞的低浓度 图像体素。然而，提高图像分辨率应该会导致 包含以下内容的体素内较高的标记细胞浓度 标记细胞，从而增强图像对比度。我们已经调查了 这一假说与费鲁马格标记T细胞的高分辨率磁共振成像 费鲁马格标记的单个细胞的位置有 已经被核磁共振成像了。Dil与T细胞共标记的荧光研究 显微镜研究提供了标记的T细胞位置的验证 样本。

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.