title: Nanoparticle enhanced MRI scanning to detect cellular inflammation in experimental chronic renal allograft rejection.
abstract: Objectives. We investigated whether ultrasmall paramagnetic particles of iron oxide- (USPIO-) enhanced magnetic resonance imaging (MRI) can detect experimental chronic allograft damage in a murine renal allograft model. Materials and Methods. Two cohorts of mice underwent renal transplantation with either a syngeneic isograft or allograft kidney. MRI scanning was performed prior to and 48 hours after USPIO infusion using T2(∗)-weighted protocols. R2(∗) values were calculated to indicate the degree of USPIO uptake. Native kidneys and skeletal muscle were imaged as reference tissues and renal explants analysed by histology and electron microscopy. Results. R2(∗) values in the allograft group were higher compared to the isograft group when indexed to native kidney (median 1.24 (interquartile range: 1.12 to 1.36) versus 0.96 (0.92 to 1.04), P < 0.01). R2(∗) values were also higher in the allograft transplant when indexed to skeletal muscle (6.24 (5.63 to 13.51)) compared to native kidney (2.91 (1.11 to 6.46) P < 0.05). Increased R2(∗) signal in kidney allograft was associated with macrophage and iron staining on histology. USPIO were identified within tissue resident macrophages on electron microscopy. Conclusion. USPIO-enhanced MRI identifies macrophage.
authors.affiliation: Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh EH16 4TJ, UK.
authors.forename: S R
authors.initials: SR
authors.lastname: Alam
authors.affiliation: MRC Centre for Inflammation Research, The University of Edinburgh, Edinburgh EH16 4TJ, UK.
authors.forename: G H
authors.initials: GH
authors.lastname: Tse
authors.affiliation: Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh EH16 4TJ, UK.
authors.forename: C
authors.initials: C
authors.lastname: Stirrat
authors.affiliation: Clinical Research Imaging Centre, University of Edinburgh, Edinburgh EH16 4TJ, UK ; Edinburgh Preclinical Imaging, University/BHF Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh EH16 4TJ, UK.
authors.forename: T J
authors.initials: TJ
authors.lastname: MacGillivray
authors.affiliation: The Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh EH16 4TJ, UK.
authors.forename: R J
authors.initials: RJ
authors.lastname: Lennen
authors.affiliation: The Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh EH16 4TJ, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Jansen
authors.affiliation: Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh EH16 4TJ, UK.
authors.forename: D E
authors.initials: DE
authors.lastname: Newby
authors.affiliation: MRC Centre for Inflammation Research, The University of Edinburgh, Edinburgh EH16 4TJ, UK.
authors.forename: L
authors.initials: L
authors.lastname: Marson
authors.affiliation: Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh EH16 4TJ, UK.
authors.forename: P A
authors.initials: PA
authors.lastname: Henriksen