NON INVASIVE DETECTION OF ORGAN REJECTION BY MRI

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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.