Magnetic resonance imaging during warm ex vivo kidney perfusion

Abstract

Background: The shortage of donor organs for transplantation remains a worldwide problem. The utilization of suboptimal deceased donors enlarges the pool of potential organs, yet consequently, clinicians face the difficult decision of whether these sub-optimal organs are of sufficient quality for transplantation. Novel technologies could play a pivotal role in making pre-transplant organ assessment more objective and reliable.

Methods: Ex vivo normothermic machine perfusion (NMP) at temperatures around 35-37°C allows organ quality assessment in a near-physiological environment. Advanced magnetic resonance imaging (MRI) techniques convey unique information about an organ's structural and functional integrity. The concept of applying magnetic resonance imaging during renal normothermic machine perfusion is novel in both renal and radiological research and we have developed the first MRI-compatible NMP setup for human-sized kidneys.

Results: We were able to obtain a detailed and real-time view of ongoing processes inside renal grafts during ex vivo perfusion. This new technique can visualize structural abnormalities, quantify regional flow distribution, renal metabolism, and local oxygen availability, and track the distribution of ex vivo administered cellular therapy.

Conclusion: This platform allows for advanced pre-transplant organ assessment, provides a new realistic tool for studies into renal physiology and metabolism, and may facilitate therapeutic tracing of pharmacological and cellular interventions to an isolated kidney.

Keywords: kidney transplantation; magnetic resonance imaging; renal physiology.

FIGURE 1

Schematic impression of our MRI‐compatible setup for ex vivo normothermic kidney perfusion [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 2

T2‐weighted images of structural abnormalities and ischemia/reperfusion damage. (A) Renal cyst not visible by visual inspection of the kidney's surface. (B) Subcapsular hematoma compressing part of the parenchyma and large intrarenal vessels. (C) Hydronephrosis due to an external obstruction of the ureter cannula. (D–F) Porcine kidney without ischemia, 60 min after induced partial ischemia (segmental area with lower T2 signal) and 30 min after reperfusion (segmental T2 signal almost recovered to its initial intensity). (G) Human discarded kidney (without intervention) with regional perfusion defect only visible on MRI.

FIGURE 3

ASL‐derived perfusion maps. Adopted from Schutter et al. (A) T2‐weighted anatomical image with a C‐shaped cortical region of interest (ROI) and several medullar ROIs drawn. (B) Overlay of T2 and ASL perfusion map. (C) ASL‐derived perfusion map in which corticomedullar ratio was calculated utilizing the ROIs that were drawn on the anatomical image. Red areas indicate a high and blue a low flow rate of the perfusate in the kidney. (D) ASL‐derived perfusion map of a human discarded kidney after 15, 30, 60, 120, and 180 min of NMP. (E) ASL‐derived perfusion map of a porcine kidney after 15, 30, 60, 120, and 180 min of NMP. [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 4

Renal metabolism imaging. (A–E): T2* map showing regional differences in oxygen availability in a porcine kidney, approximately 5 h after the start of NMP. Increased concentrations of deoxygenated Hb cause a reduced T2* signal. Perfusion in this series was with continuous pressure of 85 mm Hg. This series highlights that it takes time for deoxygenated Hb to accumulate after cessation of oxygenation and that Hb is rapidly re‐oxygenated when oxygen supply is resumed. (A) baseline perfusion (190 ml/min), oxygenated with carbogen (95% O₂/5% CO₂) at a rate of 0.5 ml/min. T2* = 50.4 ms. (B): 5 min after stopping the carbogen supply, perfusion 185 ml/min. T2* = 46.2 ms. (C) 10 min after stopping the carbogen supply, perfusion 179 ml/min. T2* = 47.8 ms. (D) 20 min after stopping the carbogen supply, perfusion 202 ml/min. T2* = 27.8 ms. T2* signal is clearly reduced due to the increased deoxygenated Hb because of the oxygen consumption without supply. (E) 5 min after the restart of carbogen supply, perfusion 214 ml/min, rapidly leading to less deoxygenated Hb. T2* = 45.3 ms. (F–I) Magnetic resonance spectroscopy providing information on lactate turnover using injected hyperpolarized [1‐13C]pyruvate in a porcine kidney. (F and G) the distribution of the hyperpolarized pyruvate tracer 6.5 and 10.5 s after the start of injection. (H and I) Signal intensities of the 13C lactate, 12 and 24 s after the start of injection for lactate. [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 5

Therapeutic tracing of mesenchymal stromal cells. Adopted from Pool et al. (A) Baseline T2‐weighted anatomical image of a porcine kidney during normothermic ex vivo perfusion (coronal view). (B) Same kidney after infusion of 1 million FeraTrack® labeled MSCs, manifesting as the dark areas in the renal cortex.