Title |
Multiparametric Functional MRI: A Tool to Uncover Subtle Changes following Allogeneic Renal Transplantation
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Published in |
PLOS ONE, November 2016
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DOI | 10.1371/journal.pone.0165532 |
Pubmed ID | |
Authors |
Mike Notohamiprodjo, Aivars Kalnins, Martin Andrassy, Manuel Kolb, Benjamin Ehle, Susanna Mueller, Michael N. Thomas, Jens Werner, Markus Guba, Konstantin Nikolaou, Joachim Andrassy |
Abstract |
To investigate multiparametric functional MRI to characterize acute rejection in a murine allogeneic renal transplant model and evaluate the effect of novel therapeutics. We performed allogeneic and syngeneic orthotopic transplantations (Balb/c to C57Bl/6 and C57Bl/6 to C57Bl/6). Allogeneic Groups (n = 5) were either treated with the anti-CCL2-Spiegelmer (mNOX-E36) in monotherapy or in combination with low doses of Ciclosporin-A (10mg/kgBW/d) for 10 days. Controls received equivalent doses of a non-functional spiegelmer (revmNOX-E36) or low dose Ciclosporin-A. Diffusion-weighted (DWI) and Dynamic-contrast-enhanced (DCE-) MRI-scans were performed using a clinical 3T-scanner. DWI analysis (b-values from 0-800 s/mm2) was performed mono- and biexponentially, while DCE-MRI was assessed with deconvolution analysis. Therapy effects were assessed ex vivo with histopathology, immunohistochemistry and RT-PCR. Statistical analysis was performed with unpaired t-tests and Spearman´s correlation coefficient. DWI showed a significant diffusion restriction in allogeneic compared to syngeneic transplants (ADC: 0.63±0.08 vs. 1.29±0.12 mm2/s*103) with decreasing diffusion restriction under therapy. DCE-MRI showed restored organ perfusion under Ciclosporin A alone and combination therapy (Plasma Flow: 43.43±12.49; 38.75±7.53ml/100ml/min) compared to syngeneic controls (51.03±12.49ml/100ml/min). Ex vivo analysis showed reduced monocytic infiltrates, attenuated levels of inflammatory cytokines under mNOX-E36 monotherapy with an additive effect of low dose Ciclosporin A. There was a significant (p<0.05) negative correlation between ADC and interstitial inflammation (r = -0.73) or macrophage infiltration (r = -0.81) and between organ perfusion and intimal arteritis (r = -0.63). Multiparametric functional MRI is suited to detect renal allograft rejection in an experimental murine model and allows to characterize effects of immunosuppressive therapy alleviating acute rejection processes in allogeneic transplantation. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 21 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 5 | 24% |
Student > Ph. D. Student | 2 | 10% |
Professor > Associate Professor | 2 | 10% |
Student > Master | 2 | 10% |
Other | 1 | 5% |
Other | 3 | 14% |
Unknown | 6 | 29% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 7 | 33% |
Agricultural and Biological Sciences | 3 | 14% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 5% |
Physics and Astronomy | 1 | 5% |
Engineering | 1 | 5% |
Other | 0 | 0% |
Unknown | 8 | 38% |