title: 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.
abstract: 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.
  
  
  RESULTS
  We have employed a rat heterotopic working-heart CR model for a magnetic resonance imaging experiment. Twenty-one allograft (PVG.1U-->PVG.R8) and 9 isograft (PVG.R8-->PVG.R8) transplantations were performed. Recipient macrophages are labeled via intravenous injection of micron-sized paramagnetic iron oxide particles (0.9 microm 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.
authors.affiliation: Department of Biological Sciences and Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.forename: Yijen L
authors.initials: YL
authors.lastname: Wu
authors.forename: Lesley M
authors.initials: LM
authors.lastname: Foley
authors.forename: T Kevin
authors.initials: TK
authors.lastname: Hitchens
authors.forename: Danielle F
authors.initials: DF
authors.lastname: Eytan
authors.forename: Haval
authors.initials: H
authors.lastname: Shirwan
authors.forename: Chien
authors.initials: C
authors.lastname: Ho
mesh_terms: D000818:Animals; D002465:Cell Movement; D005290:Ferric Compounds; D006084:Graft Rejection / Q000209:etiology*; D016027:Heart Transplantation / Q000009:adverse effects*; D008264:Macrophages / Q000502:physiology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D023421:Models, Animal; D051381:Rats; D013997:Time Factors; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
chemical_list: D005290:Ferric Compounds; C000499:ferric oxide