Volume 11 Supplement 1
Non-invasive monitoring allograft rejection by simultaneous cellular and functional cardiac MRI
© Wu et al; licensee BioMed Central Ltd. 2009
Published: 28 January 2009
The current gold standard for diagnosing and staging rejection after organ transplantation is biopsy, which is not only invasive, but is also prone to sampling errors. The regimen for treating acute rejection after heart transplantation varies among treatment centers, partly due to lack of sensitive and reliable indices for assessing the status of myocardial rejection. The goal of this study is to establish sensitive and reliable indices using cellular and functional MRI for non-invasive detection of acute cardiac allograft rejection after heart transplantation. Using a rodent model of cardiac transplantation, we monitor both immune cell infiltration and cardiac dysfunction resulting from rejection in the same imaging session. Immune cells, mainly monocytes and macrophages, are labeled in situ with dextran-coated ultra-small superparamagnetic iron oxide (USPIO) nano-particles. T2*-weighted MRI and strain analysis of tagged MRI are used to correlate immune-cell infiltration and ventricular function with rejection grades.
1. Animal model
An abdominal heterotopic working heart and lung transplantation model with DA to BN transplantation rat pairs was used. The transplanted hearts exhibit cardiac outputs and ventricular pressure similar to those of native hearts. In this model, mild (Grade 1A or B) rejection develops by post-operation day (POD) 2.5–3.5, Grade 2 rejection develops on POD 4.5–5.5, and moderate to the severe (Grade 3A) rejection develops after POD 6–7.
2. MRI methods
ECG and respiration gated T2*-weighted cine imaging on Bruker AVANCE 4.7-T system was used for in-vivo imaging with an in-plane resolution of 156 μm. Tagged MRI is achieved with a modified DANTE sequence. Strains were analyzed by the HARP method with software obtained from Diagnosoft, Inc.
3. Iron-oxide particle labeling
Immune cells, mostly macrophages, are labeled in situ by direct intravenous injection of USPIO particles 1 day prior to MRI scans.
In our model, acute allograft rejection after heart transplantation is spatially heterogeneous, which is manifested in both immune-cell infiltration and ventricular function. Cardiac MRI is both non-invasive and provides 3D, whole-heart perspective of rejection status, which potentially allows more reliable detection of acute allograft rejection.
This article is published under license to BioMed Central Ltd.