Mariager Christian Østergaard, Hansen Esben Søvsø Szocska, Bech Sabrina Kahina, Munk Anders, Kjaergaard Uffe, Lyhne Mads Dam, Søberg Karsten, Nielsen Peter Fast, Ringgaard Steffen, Laustsen Christoffer
Department of Clinical Medicine, The MR Research Centre, Aarhus University, Aarhus, Denmark.
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Magn Reson Med. 2020 Nov;84(5):2645-2655. doi: 10.1002/mrm.28363. Epub 2020 Jun 18.
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- C]pyruvate and other C-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.
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 H MRI as well as hyperpolarized [1- C]pyruvate MRI and MRS. Using the acquired anatomical, functional and metabolic data, the state of the ex vivo perfused porcine kidney could be quantified.
Four kidneys were successfully perfused for 120 minutes and verified using a DCE perfusion experiment. Renal metabolism was examined using hyperpolarized [1- C]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.
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.
常温灌注是一种新兴的供体器官保存和治疗策略，这是受全球对移植器官的高需求所推动。使用[1- C]丙酮酸和其他C标记分子的超极化磁共振成像（MRI）和磁共振波谱（MRS）提供了一种以非侵入性方式获取有关代谢和功能的高度详细信息的新方法。本研究在肾移植保存研究的背景下，探讨使用这种方法来研究和监测离体灌注猪肾的状态。
使用与磁共振兼容的灌注系统，在常温条件下用全血对来自四只40千克丹麦家猪的肾脏进行离体灌注。使用氢质子MRI以及超极化的[1- C]丙酮酸MRI和MRS对肾脏进行研究。利用获取的解剖学、功能和代谢数据，可以对离体灌注猪肾的状态进行量化。
四个肾脏成功灌注120分钟，并通过动态对比增强灌注实验进行验证。使用超极化的[1- C]丙酮酸MRI和MRS检查肾脏代谢，结果显示与体内通常情况相比，丙酮酸周转率明显降低。灌注和血气参数处于正常的离体范围内。
本研究证明了在类似于人类肾脏生理学的大型动物模型中监测离体移植物代谢和功能的能力。超极化MRI和MRS能够直接比较器官在体内和离体时的代谢状态，再结合常温灌注简单的磁共振实施方法，使这种方法成为移植保存研究未来强大的工具。
