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Studies of Acute Rejection Using Contrast Agents and Magnetic Resonance Imaging
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2006. , p. 60
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 178
Keywords [en]
Radiology, Magnetic resonance imaging, contrast agents, organ transplantation, acute rejection
Keywords [sv]
Radiologisk forskning
Identifiers
URN: urn:nbn:se:uu:diva-7169ISBN: 91-554-6670-2 (print)OAI: oai:DiVA.org:uu-7169DiVA, id: diva2:168952
Public defence
2006-10-27, Rosénsalen, Kvinnokliniken, Akademiska sjukhuset ing 95, Uppsala, 09:15
Opponent
Supervisors
Available from: 2006-10-06 Created: 2006-10-06Bibliographically approved
List of papers
1. Acute cardiac transplant rejection: Detection and grading with MR imaging with a blood pool contrast agent - experimental study in the rat
Open this publication in new window or tab >>Acute cardiac transplant rejection: Detection and grading with MR imaging with a blood pool contrast agent - experimental study in the rat
Show others...
2002 In: Radiology, Vol. 225, no 1, p. 97-103Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-94925 (URN)
Available from: 2006-10-06 Created: 2006-10-06Bibliographically approved
2. Comparison of ultrasmall superparamagnetic iron oxide particles and low molecular weight contrast agents to detect rejecting transplanted hearts with magnetic resonance imaging
Open this publication in new window or tab >>Comparison of ultrasmall superparamagnetic iron oxide particles and low molecular weight contrast agents to detect rejecting transplanted hearts with magnetic resonance imaging
2005 In: Investigative Radiology, Vol. 40, no 10, p. 648-654Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-94926 (URN)
Available from: 2006-10-06 Created: 2006-10-06Bibliographically approved
3. Macrophage uptake of ultra-small iron oxide particles for magnetic resonance imaging in experimental acute cardiac transplant rejection
Open this publication in new window or tab >>Macrophage uptake of ultra-small iron oxide particles for magnetic resonance imaging in experimental acute cardiac transplant rejection
2006 (English)In: Acta Radiologica, Vol. 3, p. 264-271Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-94927 (URN)
Available from: 2006-10-06 Created: 2006-10-06 Last updated: 2010-09-14Bibliographically approved
4. Ultrasmall iron oxide particle contrast agent and magnetic resonance imaging can be used to detect the effect of anti-rejection treatment
Open this publication in new window or tab >>Ultrasmall iron oxide particle contrast agent and magnetic resonance imaging can be used to detect the effect of anti-rejection treatment
Manuscript (Other academic)
Identifiers
urn:nbn:se:uu:diva-94928 (URN)
Available from: 2006-10-06 Created: 2006-10-06 Last updated: 2010-01-13Bibliographically approved

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