title: Noninvasive detection of graft rejection by in vivo (19) F MRI in the early stage.
abstract: Diagnosis of transplant rejection requires tissue biopsy and entails risks. Here, we describe a new (19) F MRI approach for noninvasive visualization of organ rejection via the macrophage host response. For this, we employed biochemically inert emulsified perfluorocarbons (PFCs), known to be preferentially phagocytized by monocytes and macrophages. Isografts from C57BL/6 or allografts from C57B10.A mice were heterotopically transplanted into C57BL/6 recipients. PFCs were applied intravenously followed by (1) H/(19) F MRI at 9.4 T 24 h after injection. (1) H images showed a similar position and anatomy of the graft in the abdomen for both cases. However, corresponding (19) F signals were only observed in allogenic tissue. (1) H/(19) F MRI enabled us to detect the initial immune response not later than 3 days after surgery, when conventional parameters did not reveal any signs of rejection. In allografts, the observed (19) F signal strongly increased with time and correlated with the extent of rejection. In separate experiments, rapamycin was used to demonstrate the ability of (19) F MRI to monitor immunosuppressive therapy. Thus, PFCs can serve as positive contrast agent for the early detection of transplant rejection by (19) F MRI with high spatial resolution and an excellent degree of specificity due to lack of any (19) F background.
authors.affiliation: Cardiovascular Physiology, Heinrich Heine University Düsseldorf, Germany. floegel@uni-duesseldorf.de
authors.forename: U
authors.initials: U
authors.lastname: Flögel
authors.forename: S
authors.initials: S
authors.lastname: Su
authors.forename: I
authors.initials: I
authors.lastname: Kreideweiss
authors.forename: Z
authors.initials: Z
authors.lastname: Ding
authors.forename: L
authors.initials: L
authors.lastname: Galbarz
authors.forename: J
authors.initials: J
authors.lastname: Fu
authors.forename: C
authors.initials: C
authors.lastname: Jacoby
authors.forename: O
authors.initials: O
authors.lastname: Witzke
authors.forename: J
authors.initials: J
authors.lastname: Schrader
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage; D004655:Emulsions; D005461:Fluorine; D005466:Fluorocarbons / Q000008:administration & dosage; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D016027:Heart Transplantation / Q000276:immunology / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
chemical_list: D003287:Contrast Media; D004655:Emulsions; D005466:Fluorocarbons; D005461:Fluorine