Studies of Acute Rejection Using Contrast Agents and Magnetic Resonance Imaging

• Main Author: Penno, Eva
• Format: Doctoral Thesis
• Language: English
• Published: Uppsala universitet, Institutionen för onkologi, radiologi och klinisk immunologi 2006
• Subjects: Radiology; Magnetic resonance imaging; contrast agents; organ transplantation; acute rejection; Radiologisk forskning
• Online Access: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7169; http://nbn-resolving.de/urn:isbn:91-554-6670-2

Solid organ transplantation is today an established form of treatment for end-stage organ disease. Monitoring of graft function and pharmacological therapy constitutes a maze of clinical observations and histological evaluations of biopsy specimens; with the biopsy results playing a decisive role. The aims of this doctoral research were to investigate the feasibility of detecting acute rejection of transplanted organs and monitoring the effect of anti-rejection treatment, with the use of ultrasmall superparamagnetic iron oxide particles (USPIO) and magnetic resonance (MR) imaging with a clinical MR scanner. Allogeneic and syngeneic heterotopic heart transplantations were performed in rats. Three different-sized USPIO were given to one allogeneic and one syngeneic group. The change in MR signal intensity (SI) over time was measured. An increase in SI was interpreted as damage to micro vessels due to the pronounced inflammatory reaction caused by acute rejection, which led to leakage of USPIO into the tissue. A decrease in SI was interpreted as normal vascular structure, since USPIO normally remains in the intravascular space. The same method, using one of the previously tested USPIO, was used in a treatment study in which acute rejection in transplanted rats was induced and subsequently treated. An attempt was also made to detect presence of macrophages in an acutely rejecting graft, since this cell type plays an important role in the acute rejection process; this was done by testing the ability of macrophages to phagocytose the UPSIO compound. In permeability studies with MR imaging all three USPIO tested discriminated between rejecting and non-rejecting grafts without any overlap of the groups. Factors that contributed to the ability to distinguish between grafts were the size and half-life of the particle. We were also able to monitor effects of anti-rejection treatment by studying the vascular permeability of USPIO and MR imaging. We did not succeed in detecting macrophages in the rejecting grafts with USPIO and MR imaging. This thesis presents a novel approach to detection of acute rejection of transplanted organs and to monitoring the effects of anti-rejection treatment using different USPIO contrast agents and MR imaging in a clinical MR scanner.