Dataset Information

Multiparametric Functional MRI: A Tool to Uncover Subtle Changes following Allogeneic Renal Transplantation.

ABSTRACT:

Purpose

To investigate multiparametric functional MRI to characterize acute rejection in a murine allogeneic renal transplant model and evaluate the effect of novel therapeutics.

Material and methods

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.

Results

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).

Conclusion

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.

SUBMITTER: Notohamiprodjo M

PROVIDER: S-EPMC5098737 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Multiparametric Functional MRI: A Tool to Uncover Subtle Changes following Allogeneic Renal Transplantation.

Notohamiprodjo Mike M Kalnins Aivars A Andrassy Martin M Kolb Manuel M Ehle Benjamin B Mueller Susanna S Thomas Michael N MN Werner Jens J Guba Markus M Nikolaou Konstantin K Andrassy Joachim J

PloS one 20161107 11

<h4>Purpose</h4>To investigate multiparametric functional MRI to characterize acute rejection in a murine allogeneic renal transplant model and evaluate the effect of novel therapeutics.<h4>Material and methods</h4>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 da ...[more]

PMID: 27820833

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Project description:BackgroundRenal multiparametric magnetic resonance imaging (MRI) is a promising tool for diagnosis, prognosis, and treatment monitoring in kidney disease.PurposeTo determine intrasubject test-retest repeatability of renal MRI measurements.Study typeProspective.PopulationNineteen healthy subjects aged over 40 years.Field strength/sequencesT1 and T2 mapping, R2 * mapping or blood oxygenation level-dependent (BOLD) MRI, diffusion tensor imaging (DTI), and intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI), 2D phase contrast, arterial spin labelling (ASL), dynamic contrast enhanced (DCE) MRI, and quantitative Dixon for fat quantification at 3T.AssessmentSubjects were scanned twice with ~1 week between visits. Total scan time was ~1 hour. Postprocessing included motion correction, semiautomated segmentation of cortex and medulla, and fitting of the appropriate signal model.Statistical testTo assess the repeatability, a Bland-Altman analysis was performed and coefficients of variation (CoVs), repeatability coefficients, and intraclass correlation coefficients were calculated.ResultsCoVs for relaxometry (T1 , T2 , R2 */BOLD) were below 6.1%, with the lowest CoVs for T2 maps and highest for R2 */BOLD. CoVs for all diffusion analyses were below 7.2%, except for perfusion fraction (FP ), with CoVs ranging from 18-24%. The CoV for renal sinus fat volume and percentage were both around 9%. Perfusion measurements were most repeatable with ASL (cortical perfusion only) and 2D phase contrast with CoVs of 10% and 13%, respectively. DCE perfusion had a CoV of 16%, while single kidney glomerular filtration rate (GFR) had a CoV of 13%. Repeatability coefficients (RCs) ranged from 7.7-87% (lowest/highest values for medullary mean diffusivity and cortical FP , respectively) and intraclass correlation coefficients (ICCs) ranged from -0.01 to 0.98 (lowest/highest values for cortical FP and renal sinus fat volume, respectively).Data conclusionCoVs of most MRI measures of renal function and structure (with the exception of FP and perfusion as measured by DCE) were below 13%, which is comparable to standard clinical tests in nephrology.Level of evidence2 TECHNICAL EFFICACY: Stage 1.

Dataset Information

Multiparametric Functional MRI: A Tool to Uncover Subtle Changes following Allogeneic Renal Transplantation.

Purpose

Material and methods

Results

Conclusion

Publications

Multiparametric Functional MRI: A Tool to Uncover Subtle Changes following Allogeneic Renal Transplantation.

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