Sodium Hydrosulfide Treatment During Porcine Kidney Ex Vivo Perfusion and Transplantation.

Background: In rodents, hydrogen sulfide (H2S) reduces ischemia-reperfusion injury and improves renal graft function after transplantation. Here, we hypothesized that the benefits of H2S are conserved in pigs, a more clinically relevant model. Methods: Adult porcine kidneys retrieved immediately or after 60 min of warm ischemia (WI) were exposed to 100 µM sodium hydrosulfide (NaHS) (1) during the hypothermic ex vivo perfusion only, (2) during WI only, and (3) during both WI and ex vivo perfusion. Kidney perfusion was evaluated with dynamic contrast-enhanced MRI. MRI spectroscopy was further employed to assess energy metabolites including ATP. Renal biopsies were collected at various time points for histopathological analysis. Results: Perfusion for 4 h pig kidneys with Belzer MPS UW + NaHS resulted in similar renal perfusion and ATP levels than perfusion with UW alone. Similarly, no difference was observed when NaHS was administered in the renal artery before ischemia. After autotransplantation, no improvement in histologic lesions or cortical/medullary kidney perfusion was observed upon H2S administration. In addition, AMP and ATP levels were identical in both groups. Conclusions: In conclusion, treatment of porcine kidney grafts using NaHS did not result in a significant reduction of ischemia-reperfusion injury or improvement of kidney metabolism. Future studies will need to define the benefits of H2S in human, possibly using other molecules as H2S donors.

In vivo magnetic resonance 31 P-Spectral Analysis With Neural Networks: 31P-SPAWNN.

PURPOSE: We have introduced an artificial intelligence framework, 31P-SPAWNN, in order to fully analyze phosphorus-31 ( 31 $$ {}^{31} $$ P) magnetic resonance spectra. The flexibility and speed of the technique rival traditional least-square fitting methods, with the performance of the two approaches, are compared in this work. THEORY AND METHODS: Convolutional neural network architectures have been proposed for the analysis and quantification of 31 $$ {}^{31} $$ P-spectroscopy. The generation of training and test data using a fully parameterized model is presented herein. In vivo unlocalized free induction decay and three-dimensional 31 $$ {}^{31} $$ P-magnetic resonance spectroscopy imaging data were acquired from healthy volunteers before being quantified using either 31P-SPAWNN or traditional least-square fitting techniques. RESULTS: The presented experiment has demonstrated both the reliability and accuracy of 31P-SPAWNN for estimating metabolite concentrations and spectral parameters. Simulated test data showed improved quantification using 31P-SPAWNN compared with LCModel. In vivo data analysis revealed higher accuracy at low signal-to-noise ratio using 31P-SPAWNN, yet with equivalent precision. Processing time using 31P-SPAWNN can be further shortened up to two orders of magnitude. CONCLUSION: The accuracy, reliability, and computational speed of the method open new perspectives for integrating these applications in a clinical setting.

Choreography Controlled (ChoCo) brain MRI artifact generation for labeled motion-corrupted datasets.

MRI is a non-invasive medical imaging modality that is sensitive to patient motion, which constitutes a major limitation in most clinical applications. Solutions may arise from the reduction of acquisition times or from motion-correction techniques, either prospective or retrospective. Benchmarking the latter methods requires labeled motion-corrupted datasets, which are uncommon. Up to our best knowledge, no protocol for generating labeled datasets of MRI images corrupted by controlled motion has yet been proposed. Hence, we present a methodology allowing the acquisition of reproducible motion-corrupted MRI images as well as validation of the system's performance by motion estimation through rigid-body volume registration of fast 3D echo-planar imaging (EPI) time series. A proof-of-concept is presented, to show how the protocol can be implemented to provide qualitative and quantitative results. An MRI-compatible video system displays a moving target that volunteers equipped with customized plastic glasses must follow to perform predefined head choreographies. Motion estimation using rigid-body EPI time series registration demonstrated that head position can be accurately determined (with an average standard deviation of about 0.39 degrees). A spatio-temporal upsampling and interpolation method to cope with fast motion is also proposed in order to improve motion estimation. The proposed protocol is versatile and straightforward. It is compatible with all MRI systems and may provide insights on the origins of specific motion artifacts. The MRI and artificial intelligence research communities could benefit from this work to build in-vivo labeled datasets of motion-corrupted MRI images suitable for training/testing any retrospective motion correction or machine learning algorithm.

Subnormothermic Ex Vivo Porcine Kidney Perfusion Improves Energy Metabolism: Analysis Using 31P Magnetic Resonance Spectroscopic Imaging.

The ideal preservation temperature for donation after circulatory death kidney grafts is unknown. We investigated whether subnormothermic (22 °C) ex vivo kidney machine perfusion could improve kidney metabolism and reduce ischemia-reperfusion injury. Methods: To mimic donation after circulatory death procurement, kidneys from 45-kg pigs underwent 60 min of warm ischemia. Kidneys were then perfused ex vivo for 4 h with Belzer machine perfusion solution UW at 22 °C or at 4 °C before transplantation. Magnetic resonance spectroscopic imaging coupled with LCModel fitting was used to assess energy metabolites. Kidney perfusion was evaluated with dynamic-contrast enhanced MRI. Renal biopsies were collected at various time points for histopathologic analysis. Results: Total adenosine triphosphate content was 4 times higher during ex vivo perfusion at 22 °C than at 4 °C perfusion. At 22 °C, adenosine triphosphate levels increased during the first hours of perfusion but declined afterward. Similarly, phosphomonoesters, containing adenosine monophosphate, were increased at 22 °C and then slowly consumed over time. Compared with 4 °C, ex vivo perfusion at 22 °C improved cortical and medullary perfusion. Finally, kidney perfusion at 22 °C reduced histological lesions after transplantation (injury score: 22 °C: 10.5 ± 3.5; 4 °C: 18 ± 2.25 over 30). Conclusions: Ex vivo kidney perfusion at 22°C improved graft metabolism and protected from ischemia-reperfusion injuries upon transplantation. Future clinical studies will need to define the benefits of subnormothermic perfusion in improving kidney graft function and patient's survival.

Ex Vivo Analysis of Kidney Graft Viability Using 31P Magnetic Resonance Imaging Spectroscopy.

BACKGROUND: The lack of organs for kidney transplantation is a growing concern. Expansion in organ supply has been proposed through the use of organs after circulatory death (donation after circulatory death [DCD]). However, many DCD grafts are discarded because of long warm ischemia times, and the absence of reliable measure of kidney viability. P magnetic resonance imaging (pMRI) spectroscopy is a noninvasive method to detect high-energy phosphate metabolites, such as ATP. Thus, pMRI could predict kidney energy state, and its viability before transplantation. METHODS: To mimic DCD, pig kidneys underwent 0, 30, or 60 min of warm ischemia, before hypothermic machine perfusion. During the ex vivo perfusion, we assessed energy metabolites using pMRI. In addition, we performed Gadolinium perfusion sequences. Each sample underwent histopathological analyzing and scoring. Energy status and kidney perfusion were correlated with kidney injury. RESULTS: Using pMRI, we found that in pig kidney, ATP was rapidly generated in presence of oxygen (100 kPa), which remained stable up to 22 h. Warm ischemia (30 and 60 min) induced significant histological damages, delayed cortical and medullary Gadolinium elimination (perfusion), and reduced ATP levels, but not its precursors (AMP). Finally, ATP levels and kidney perfusion both inversely correlated with the severity of kidney histological injury. CONCLUSIONS: ATP levels, and kidney perfusion measurements using pMRI, are biomarkers of kidney injury after warm ischemia. Future work will define the role of pMRI in predicting kidney graft and patient's survival.