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(Circulation. 2008;118:149-156.)
© 2008 American Heart Association, Inc.

Imaging

Longitudinal Tracking of Recipient Macrophages in a Rat Chronic Cardiac Allograft Rejection Model With Noninvasive Magnetic Resonance Imaging Using Micrometer-Sized Paramagnetic Iron Oxide Particles

Qing Ye, MD; Yijen L. Wu, PhD; Lesley M. Foley, BS; T. Kevin Hitchens, PhD; Danielle F. Eytan; Haval Shirwan, PhD; Chien Ho, PhD

From the Department of Biological Sciences and Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, Pa (Q.Y., Y.L.W., L.M.F., T.K.H., D.F.E., C.H.); and Institute for Cellular Therapeutics and Department of Microbiology and Immunology, University of Louisville, Louisville, Ky (H.S.).

Correspondence to Chien Ho, PhD, Department of Biological Sciences, Carnegie Mellon University, 4400 Fifth Ave, Pittsburgh, PA 15213. E-mail chienho{at}andrew.cmu.edu

Received October 17, 2007; accepted May 7, 2008.

Background— Long-term survival of heart transplants is hampered by chronic rejection (CR). Studies indicate the involvement of host macrophages in the development of CR; however, the precise role of these cells in CR is unclear. Thus, it is important to develop noninvasive techniques to serially monitor the movement and distribution of recipient macrophages in chronic cardiac allograft rejection in vivo.

Methods and Results— We have employed a rat heterotopic working-heart CR model for a magnetic resonance imaging experiment. Twenty-one allograft (PVG.1UPVG.R8) and 9 isograft (PVG.R8PVG.R8) transplantations were performed. Recipient macrophages are labeled via intravenous injection of micron-sized paramagnetic iron oxide particles (0.9 µm in diameter) at a dose of 4.5 mg Fe per rat 1 day before transplantation. Serial in vivo magnetic resonance images were acquired for up to 16 weeks. The migration of labeled recipient cells in our CR model, in which cardiac CR is evident at 3 weeks and most extensive by 16 weeks after transplantation, can be assessed with the use of in vivo magnetic resonance imaging for >100 days after a single micron-sized paramagnetic iron oxide injection. The location and distribution of labeled recipient cells were confirmed with magnetic resonance microscopy and histology.

Conclusions— This approach may improve our understanding of the immune cells involved in CR and the management of heart transplantation. Moreover, this study demonstrates the feasibility of noninvasively observing individual targeted cells over long time periods by serial in vivo magnetic resonance imaging.

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CLINICAL PERSPECTIVE

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Clinical Summaries
Circulation 2008 118: 105-106. [Extract] [Full Text]

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