From the Institute for Biomedical Engineering, University and ETH Zurich, Gloriastrasse 35, 8092 Zurich, Switzerland (D.O., P.W., J.B., L.W., M.K., K.W., A.S., S.K.); Departments of Congenital Heart Disease and Pediatric Cardiology (D.O., D.M.) and Internal Medicine, Division of Cardiology (D.M.), German Heart Institute, Berlin, Germany; and Division of Imaging Sciences and Biomedical Engineering, King's College London, London, England (D.O., S.K.).
Radiology. 2016 Mar;278(3):742-51. doi: 10.1148/radiol.2015151332. Epub 2015 Nov 23.
To implement hyperpolarized magnetic resonance (MR) imaging in an animal model of ischemia-reperfusion and to assess in vivo the regional changes in pyruvate metabolism within the 1st hour and at 1 week after a brief episode of coronary occlusion and reperfusion.
All animal experiments were performed with adherence to the Swiss Animal Protection law and were approved by the regional veterinary office. A closed-chest rat model was implemented by using an inflatable balloon secured around the left coronary artery. Animals were placed in an MR system 5-7 days after surgery. [1-(13)C]pyruvate was polarized by using a home-built multisample hyperpolarizer. Hyperpolarized pyruvate was injected at five stages: at baseline; at reperfusion after 15 minutes of coronary occlusion; and at 30 minutes, 60 minutes, and 1 week after ischemia reperfusion. The conversion of pyruvate into lactate and bicarbonate was imaged by using dedicated MR sequences alongside wall motion and delayed enhancement imaging. After imaging, the heart was removed and stained to delineate the area at risk (AAR). Differences between AAR and remote myocardium were assessed by using a repeated measures analysis of variance and a post hoc Bonferroni multiple comparison test.
Data were collected in 12 animals. Occlusion led to hypokinesia of the anterior or anterolateral segments of the myocardium. At reperfusion, the average lactate-to-bicarbonate ratio increased in the AAR relative to that at baseline (from 1.93 ± 0.48 to 3.01 ± 0.74, P < .001) and was significantly higher when compared with that in the remote area (1.91 ± 0.38, P < .001). In the 60 minutes after occlusion, the lactate-to-bicarbonate ratio in the AAR recovered but was still elevated relative to that in the remote area. One week after ischemia-reperfusion, no difference between AAR and remote area could be detected.
Hyperpolarized metabolic MR imaging can be used to successfully detect acute changes in [1-(13)C]pyruvate metabolism after ischemia-reperfusion, thereby enabling in vivo monitoring of the metabolic effects of reperfusion strategies.
在缺血再灌注动物模型中实现超极化磁共振（MR）成像，并评估短暂冠状动脉闭塞和再灌注后 1 小时内和 1 周内丙酮酸代谢的区域变化。
所有动物实验均严格遵守瑞士动物保护法，并经地区兽医办公室批准。采用固定在左冠状动脉周围的可充气气球建立闭胸大鼠模型。手术后 5-7 天，将动物置于 MR 系统中。使用自制的多样本超极化器对 [1-（13）C]丙酮酸进行极化。在基线时、冠状动脉闭塞 15 分钟后再灌注时以及缺血再灌注后 30 分钟、60 分钟和 1 周时，分别在五个阶段注射超极化丙酮酸。通过专门的 MR 序列对丙酮酸转化为乳酸盐和碳酸氢盐的过程进行成像，并结合壁运动和延迟增强成像。成像后，取出心脏并染色以描绘危险区（AAR）。采用重复测量方差分析和事后 Bonferroni 多重比较检验评估 AAR 与远隔心肌之间的差异。
共收集了 12 只动物的数据。闭塞导致心肌的前或前外侧节段运动减弱。再灌注时，AAR 与基线相比，乳酸盐与碳酸氢盐的比值（从 1.93±0.48 增加至 3.01±0.74，P<.001）增加，且明显高于远隔区（1.91±0.38，P<.001）。闭塞后 60 分钟，AAR 中的乳酸盐与碳酸氢盐比值恢复，但仍高于远隔区。缺血再灌注后 1 周，AAR 与远隔区之间无差异。
超极化代谢磁共振成像可成功检测缺血再灌注后 [1-（13）C]丙酮酸代谢的急性变化，从而实现再灌注策略代谢效果的体内监测。
