Graft assessment of the ex vivo perfused porcine kidney using hyperpolarized [1‐¹³C]pyruvate

Abstract

Purpose Normothermic perfusion is an emerging strategy for donor organ preservation and therapy, incited by the high worldwide demand for organs for transplantation. Hyperpolarized MRI and MRS using [1‐13C]pyruvate and other 13C‐labeled molecules pose a novel way to acquire highly detailed information about metabolism and function in a noninvasive manner. This study investigates the use of this methodology as a means to study and monitor the state of ex vivo perfused porcine kidneys, in the context of kidney graft preservation research. Methods Kidneys from four 40‐kg Danish domestic pigs were perfused ex vivo with whole blood under normothermic conditions, using an MR‐compatible perfusion system. Kidneys were investigated using 1H MRI as well as hyperpolarized [1‐13C]pyruvate MRI and MRS. Using the acquired anatomical, functional and metabolic data, the state of the ex vivo perfused porcine kidney could be quantified. Results Four kidneys were successfully perfused for 120 minutes and verified using a DCE perfusion experiment. Renal metabolism was examined using hyperpolarized [1‐13C]pyruvate MRI and MRS, and displayed an apparent reduction in pyruvate turnover compared with the usual case in vivo. Perfusion and blood gas parameters were in the normal ex vivo range. Conclusion This study demonstrates the ability to monitor ex vivo graft metabolism and function in a large animal model, resembling human renal physiology. The ability of hyperpolarized MRI and MRS to directly compare the metabolic state of an organ in vivo and ex vivo, in combination with the simple MR implementation of normothermic perfusion, renders this methodology a powerful future tool for graft preservation research.

Development of a human heart‐sized perfusion system for metabolic imaging studies using hyperpolarized [1‐13C]pyruvate MRI

“…Our in‐house‐built MRI compatible large‐organ perfusion system was previously described and successfully feasibility tested for use in ex vivo renal research, using porcine kidney grafts 48 . In the present case, however, the cyclic motion of the heart called for improvements to the experimental set‐up.…”

“…Additional blood gas analysis produced glucose and pH values in the physiological range. The high initial blood lactate values could potentially be because of insufficient cooling of the perfusate blood, as previously described 48 . With regard to the delivery and dose of administered hyperpolarized [1‐ 13 C]pyruvate, the in vivo and ex vivo situations also differ slightly.…”

“…Anesthesia was administered using intravenous propofol at 2.5 mg/kg/h and fentanyl at 0.15 mg/kg/h, as previously described. 48 6F introducer sheaths were established in the right femoral artery and left femoral vein by means of an ultrasound-guided Seldinger technique, allowing for medicine infusion, blood sampling, and monitoring of arterial blood pressure. For comparison, previously published data from four in vivo porcine cardiac studies were also included.…”

“…An MRI compatible perfusion system developed for normothermic perfusion of large animal organs 48,49 was adapted to this protocol and primed using Ringer's lactate solution (Fresenius Kabi) removing all air (Figure 1A). A custom glass perfusion chamber was prepared to receive the heart (Figure 1A,B and Supporting Information Figure S1A,B).…”

“…Here we present our MRI-compatible normothermic perfusion system, 48,49 adapted to the ex vivo Langendorff perfusion of porcine heart grafts. The system allows for hemodynamic measurement, detailed metabolic mapping, and functional assessment using hyperpolarized MR and CMR, thereby providing a flexible MR-based platform for preclinical heart graft research capable of enhancing the achievements already obtained by systems such as the TransMedics OCS.…”