双时相18F-FDG心肌缺血显像的机制研究和方法学建立

18F-FDG myocardial imaging under fasting station has been demonstrated to be a sensitive modality in detection of coronary artery disease. Nevertheless, due to the non-specific 18F-FDG uptake of normal myocardium under fasting condition, 18F-FDG myocardial ischemic imaging has inferior diagnostic specificity. In prior study, we found that 18F-FDG uptake in normal myocardium didn't change significantly within a short period (2 h) wherease ischemic myocardium displayed remarkeble increase of 18F-FDG uptake after stress-induced ischemia. Therefore, ischemic myocardium can be easily discriminated from normal myocardium using 18F-FDG dual-phase imaging.In the present study,we will explore the molecular mechanism and imaging methodology of dual-phase 18F-FDG myocardial ischemic imaging using porcine model with chronic coronary stenosis. Myocardial ischemia will be induced using dobutamine stress test, danymic 18F-FDG PET/CT images acquisition will be started 62 min before stress test and lasted for 130 min. Myocardial glucose uptake of the early and delayed imaging will be compared. After imaging study,hearts will be excised and glucose transporter genes will be analyzed and compared between the normal and ischemic myocardium. The study will provide theoretical and experimental data for the further application of 18F-FDG myocardial ischemic imaging.

18F-FDG心肌缺血显像是诊断冠心病心肌缺血的新技术，其灵敏度优于心肌灌注显像。但是，空腹状态下，正常心肌也会有不同程度的18F-FDG摄取，因此该方法的特异性欠佳。我们在前期研究中发现，如果在心肌缺血前后的短时间内（<2小时）分别进行心肌18F-FDG显像（双时相显像），则缺血心肌的18F-FDG摄取变化显著，而正常心肌变化不明显。因此，双时相采集有望显著提高该方法的特异性。在本研究中，我们拟在慢性冠状动脉狭窄的动物模型，用多巴酚丁胺诱发心肌缺血，利用PCR和Western Blot分析双时相显像葡萄糖代谢相关基因和蛋白表达的变化，并用PET定量分析正常心肌和缺血心肌葡萄糖摄取在双时相显像时的变化特征，从而探讨双时相心肌缺血显像的机制。同时，通过PET动态显像、比较18F-FDG注射方式等探索科学可行的显像方案。为促进18F-FDG心肌缺血显像的应用提供理论和实验基础。

18F-FDG心肌缺血显像可以通过显示缺血心肌的葡萄糖异常代谢来诊断冠心病心肌缺血，但在实际应用中由于正常心肌也存在18F-FDG的非特异性摄取从而增加了诊断心肌缺血的假阳性概率。本课题通过建立实验猪慢性心肌缺血模型，创新性的观察多巴酚丁胺负荷前后（双时相）短时间内的心肌葡萄糖代谢变化来判断心肌缺血，利用PET定性分析正常心肌和缺血心肌葡萄糖摄取在双时相显像时的变化特征，并通过PET动态显像，探索科学可行的显像方案,为促进18F-FDG心肌缺血显像的应用提供理论和实验基础。实验结果显示，基础显像时13头正常实验猪有12头通过双时相显像诊断为正常，特异度达97%，缺血显像下，以冠脉造影为标准，13头猪的左前降支狭窄程度均大于70%，其中4头经双时相显像判断为心肌缺血；加做负荷心肌灌注显像并提示心肌缺血的6头实验猪中，双时相显像发现了4头，灵敏度为67%。因此双时相18F-FDG显像在探测猪慢性心肌缺血方面具有一定的灵敏度和较高的特异性。