NON INVASIVE DETECTION OF ORGAN REJECTION BY MRI

这个项目的目标是开发方法来标记一个特定的 用MRI可检测的造影剂检测细胞类型， 通过MRI在活体动物中非侵入性地移动这些标记的细胞 技术. 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细胞是急性移植排斥反应的主要效应细胞。 我们希望 通过MRI跟踪T细胞“归巢”到移植部位 通过用MR可检测的造影剂标记T细胞的排斥反应。 葡聚糖包被的超顺磁性氧化铁（SPIO）颗粒已经被研究。 用作MR造影剂，但它们目前在商业上没有 available. 我们已经合成了自己的葡聚糖涂层SPIO颗粒， 称为Ferumag，其具有可比较的特性 与之前获得的商业样品进行比对。 T细胞标记有 Ferumag颗粒通过内吞作用，产生标记效率 大约20%。 内吞条件的几点改进 提高了标记效率。 进一步 提高检测器官排斥反应的灵敏度， 目前正在探索培养T细胞的可能性， 具体到捐助者，以便他们将有选择地回家， 排斥部位。 追踪细胞迁移的主要困难是 MRI一直是低灵敏度，因为人口稀少， 标记的T细胞导致细胞内低浓度的标记细胞， 图像体素。 然而，提高图像分辨率应该会导致 体素内较高的标记细胞浓度， 标记的细胞，从而增强图像对比度。 我们已经调查 该假设使用Ferumag标记的T细胞的高分辨率MRI 其中Ferumag标记的单细胞位置具有 通过MRI成像。 用Dil共标记T细胞用于荧光 显微镜研究提供了标记的T细胞位置的验证， 示例.

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.