Objectives: Marginal donor kidneys are increasingly used for transplantation to overcome organ shortage. This study aims to investigate the additional value of Power Doppler (PD) imaging in kidney quality assessment during normothermic machine perfusion (NMP). Methods: Porcine kidneys (n = 22) retrieved from a local slaughterhouse underwent 2 h of NMP. Based on creatinine clearance (CrCl) and oxygen consumption (VO₂) at 120 min, kidneys were classified into Group 1 (n = 7, CrCl > 1 mL/min/100 g and VO₂ > 2.6 mL/min/100 g) and Group 2 (n = 15, CrCl ≤ 1 mL/min/100 g and/or VO₂ ≤ 2.6 mL/min/100 g). PD imaging was performed at 30, 60, and 120 min, and PD metrics, including vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were calculated. Renal blood flow (RBF), CrCl, and VO₂ were measured at the same time points during NMP. The metrics were compared utilizing correlation analysis. Results: FI and VFI moderately correlated with CrCl (r = 0.537, p < 0.0001; r = 0.536, p < 0.0001, respectively), while VI strongly correlated with VO₂ (r = 0.839, p < 0.0001). At 120 min, PD metrics demonstrated the highest diagnostic accuracy for distinguishing between the two groups, with an area under the curve (AUC) of 0.943 for VI, 0.924 for FI, and 0.943 for VFI. Cutoff values of 17% for VI, 50 a.u. for FI, and 9 a.u. for VFI provided 100% specificity and 73% sensitivity in identifying kidneys in Group 2, with an overall diagnostic accuracy of 82%. Baseline kidney biopsies showed moderate acute tubular necrosis in both groups, with no significant differences. Conclusions: PD metrics strongly correlate with renal viability and effectively differentiate kidneys with higher and lower functionality during NMP. PD imaging can be a valuable alternative to RBF during NMP for kidney quality assessment.

Due to the shortage of kidneys donated for transplantation, surgeons are forced to use the organs with an elevated risk of poor function or even failure. Although the existing methods for pre-transplant quality evaluation have been validated over decades in population cohort studies across the world, new methods are needed as long as delayed graft function or failure in a kidney transplant occurs. In this study, we explored the potential of utilizing photoacoustic (PA) imaging during normothermic machine perfusion (NMP) as a means of evaluating kidney quality. We closely monitored twenty-two porcine kidneys using 3D PA imaging during a two-hour NMP session. Based on biochemical analyses of perfusate and produced urine, the kidneys were categorized into ‘non-functional’ and ‘functional’ groups. Our primary focus was to quantify oxygenation (sO₂) within the kidney cortical layer of depths 2 mm, 4 mm, and 6 mm using two-wavelength PA imaging. Next, receiver operating characteristic (ROC) analysis was performed to determine an optimal cortical layer depth and time point for the quantification of sO₂ to discriminate between functional and non-functional organs. Finally, for each depth, we assessed the correlation between sO₂ and creatinine clearance (CrCl), oxygen consumption (VO₂), and renal blood flow (RBF). We found that hypoxia of the renal cortex is associated with poor renal function. In addition, the determination of sO₂ within the 2 mm depth of the renal cortex after 30 min of NMP effectively distinguishes between functional and non-functional kidneys. The non-functional kidneys can be detected with the sensitivity and specificity of 80% and 85% respectively, using the cut-off point of sO₂ < 39%. Oxygenation significantly correlates with RBF and VO₂ in all kidneys. In functional kidneys, sO₂ correlated with CrCl, which is not the case for non-functional kidneys. We conclude that the presented technique has a high potential for supporting organ selection for kidney transplantation.

The use of nanoparticles as tumor-targeting agents is steadily increasing, and the influence of nanoparticle characteristics such as size and stealthiness have been established for a large number of nanocarrier systems. However, not much is known about the impact of tumor presence on nanocarrier circulation times. This paper reports on the influence of tumor presence on the in vivo circulation time and biodistribution of polybutadiene-polyethylene oxide (PBd-PEO) polymersomes. For this purpose, polymersomes were loaded with the gamma-emitter¹¹¹In and administered intravenously, followed by timed ex vivo biodistribution. A large reduction in circulation time was observed for tumor-bearing mice, with a circulation half-life of merely 5 min (R² = 0.98) vs 117 min (R² = 0.95) in healthy mice. To determine whether the rapid polymersome clearance observed in tumor-bearing mice was mediated by macrophages, chlodronate liposomes were administered to both healthy and tumor-bearing mice prior to the intravenous injection of radiolabeled polymersomes to deplete their macrophages. Pretreatment with chlodronate liposomes depleted macrophages in the spleen and liver and restored the circulation time of the polymersomes with no significant difference in circulation time between healthy mice and tumor-bearing mice pretreated with clodronate liposomes (15.2 ± 1.2% ID/g and 13.6 ± 2.7% ID/g, respectively, at 4 h p.i. with p = 0.3). This indicates that activation of macrophages due to tumor presence indeed affected polymersome clearance rate. Thus, next to particle design, the presence of a tumor can also greatly impact circulation times and should be taken into account when designing studies to evaluate the distribution of polymersomes.