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.
Highlights
Chronic allograft damage (CAD), characterised by interstitial fibrosis and tubular atrophy (IFTA), is the commonest cause of transplant failure following surgery [1]
We have developed a model of chronic allograft damage: characterised by a single class II mismatch a kidney from C57BL/6BM12 (H-2BBM12) donor is transplanted into a C57BL/6 (H-2B) recipient and leads to the progressive development of interstitial fibrosis and tubular atrophy (IFTA) over 4 to 8 weeks
Illustrative magnetic resonance imaging (MRI) scans with R2∗ signal derived colour maps of USPIO uptake in allograft and isograft kidneys are shown in Figures 1(a) and 1(b)
Summary
Chronic allograft damage (CAD), characterised by interstitial fibrosis and tubular atrophy (IFTA), is the commonest cause of transplant failure following surgery [1]. The demand for organ transplantation is expanding and waiting lists for a kidney are likely to increase in coming years [2]. Identification of chronic allograft damage remains challenging but is crucial to allow intervention with immunosuppressive therapy. Renal biopsy remains the gold-standard for detecting allograft rejection but is associated with significant morbidity and mortality. It would be advantageous to have a noninvasive imaging approach for the detection of acute rejection and IFTA. This would provide an alternative or adjunctive clinical assessment that may reduce the number of biopsies
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