title: Quantification of islet loss and graft functionality during immune rejection by 3-tesla MRI in a rat model.
abstract: BACKGROUND
  Because metabolic markers are not suitable for early diagnosis of islet graft dysfunction, magnetic resonance imaging (MRI) has been used to study islets that were labeled pretransplantation with superparamagnetic iron oxide nanoparticles. However, the relation between graft functionality assessed by glycemia, and MRI signal remains unclear.
  
  
  METHODS
  We transplanted hyperglycemic rats intraportally with 2500 ferucarbotran-labeled syngeneic (n=10) or allogeneic (n=12) islet equivalents or normoglycemic rats with 5000 xenogeneic human islet equivalents. Images were acquired on a clinical 3-Tesla MRI scanner.
  
  
  RESULTS
  When rejection occurred on days 4 and 8 in xenogeneic and allogeneic recipients, 60% (57-68) and 55% (46-73) of the initial signal remained compared to 93% (71-104) and 82% (59-90) in syngeneic controls (P=0.006 and 0.03). With a cutoff value of 84% on day 4 for the diagnosis of allogeneic rejection, sensitivity of 91% and specificity of 70% were obtained. Based on MRI signal on day 4, treatment with antilymphocytic serum from day 4 allowed graft rescue in 75% of recipients.
  
  
  CONCLUSIONS
  In this model, MRI of pretransplantation superparamagnetic iron oxide nanoparticle-labeled islet grafts allows timely diagnosis of immune rejection.
authors.affiliation: Cell Isolation and Transplant Center, Department of Surgery, University of Geneva and Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Sophie
authors.initials: S
authors.lastname: Borot
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Crowe
authors.forename: Géraldine
authors.initials: G
authors.lastname: Parnaud
authors.forename: Frédéric
authors.initials: F
authors.lastname: Ris
authors.forename: Raphael
authors.initials: R
authors.lastname: Meier
authors.forename: Laurianne
authors.initials: L
authors.lastname: Giovannoni
authors.forename: Yannick D
authors.initials: YD
authors.lastname: Müller
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Lacotte
authors.forename: Philippe
authors.initials: P
authors.lastname: Morel
authors.forename: Christian
authors.initials: C
authors.lastname: Toso
authors.forename: Domenico
authors.initials: D
authors.lastname: Bosco
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Vallee
authors.forename: Thierry
authors.initials: T
authors.lastname: Berney
mesh_terms: D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D006084:Graft Rejection / Q000175:diagnosis*; D007165:Immunosuppression Therapy; D007515:Islets of Langerhans / Q000473:pathology*; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew
chemical_list: D000961:Antilymphocyte Serum; D058185:Magnetite Nanoparticles