光声成像技术评估心肌缺血和再灌注的活体研究

发布时间：2018-04-19 13:31

本文选题：光声成像技术 + 急性心肌缺血　；参考：《福建医科大学》2015年博士论文

【摘要】：研究背景和目的:心肌缺血和再灌注在心血管疾病发展过程中至关重要。目前评估心肌血流灌注的检查方法各有优缺点,但都不能完全满足临床需求。光声成像技术(photoacoustic imaging technology,PAT)结合光学和超声的优点,具有分辨率高、对比度高、成像深度深等特点,并且没有辐射危害。本次研究在原有基础上,以新西兰白兔为实验对象,分别建立急性心肌缺血、急性心肌缺血再灌注和慢性心肌缺血三种动物模型。采用成像速度更快、分辨率更高的PAT系统,以血红蛋白作为天然“造影剂”,在兔活体心脏上面进行PAT三维成像,探讨其评估心肌缺血和再灌注的可行性。1.急性心肌缺血光声成像方法将42只新西兰白兔(2.78±0.23Kg)随机分成两组:急性缺血组直接结扎左旋支建立急性心肌缺血模型,分别建立结扎0.5h、1h、2h、3h、4h、6h模型,每个时间点6只;另6只仅穿线不打结,建立假手术6h为对照组。分别在不同时间点描记心电图;采血检测血清心肌损伤标志物(c Tn I、CK-MB);并在缺血区域进行PAT成像,计算灰度值和总量。实验后取心脏行HE染色、TUNEL凋亡检测,计算病理学指标(半定量评分SAS、细胞凋亡指数AI)。结果急性缺血组血清心肌损伤标志物、病理学指标均随结扎时间的延长呈增高趋势(P0.05),而结扎6h组AI值比结扎4h组小(P0.05)。PAT指标(灰度值、总量)均随结扎时间的延长呈下降趋势(P0.05)。PAT指标与血清心肌损伤标志物、病理学指标呈负相关(P0.05)。结论急性心肌缺血6h内,心肌缺血损伤随时间延长而加重;灰度值、总量随时间增加而降低。PAT可以用于评估急性心肌缺血程度和范围,灰度值、总量均与心肌缺血损伤呈反比。2.急性心肌缺血再灌注光声成像方法将24只新西兰白兔(2.77±0.24Kg)分为再灌注组,以结扎左旋支2h后开放建立急性心肌缺血再灌注模型:随机分成4个小组,每个小组6只,分别建立开放0.5h、1h、2h、4h再灌注模型。分别在不同时间点描记心电图;采血检测血清心肌损伤标志物;并在缺血区域进行PAT成像,计算灰度值和总量。实验后取心脏行HE染色、TUNEL凋亡检测等组织病理学,并技术病理学指标。并分别与急性缺血组结扎3h、4h、6h等相应时间进行比较。取结扎2h组、假手术6h组作为对照组。结果再灌注组血清心肌损伤标志物及病理学指标随开放时间增加呈增高趋势(P0.05),除了开放4h组AI值小于开放2h组(P0.05)。但开放4h组血清心肌损伤标志物及SAS均比结扎6h组低(P0.05);而开放4h组AI比结扎6h高(P0.05)。灰度值和总量均随开放时间延长呈增高趋势(P0.05)。而开放4h组灰度值与对照组比较无差异(P0.05),开放4h组总量较对照组低(P0.05)。PAT指标与血清心肌损伤标志物、病理学指标呈正相关(P0.05)。结论结扎2h再灌注4h内,随再灌注时间增加,心肌损伤加重,但是加重的幅度小于急性缺血组;PAT灰度值和总量与心肌损伤呈正比;开放4h组总量没有恢复到对照组水平,可能与无复流现象有关。PAT可以用于评估急性心肌缺血再灌注程度和范围。3.慢性心肌缺血光声成像方法将13只新西兰白兔(2.60±0.20Kg)随机分成两组,实验组取10只在左旋支安置Ameroid缩窄器,建立慢性心肌缺血模型;对照组取3只,只开胸,不放置Ameroid缩窄器。建模后第5周采血检测心肌损伤标志物;并经右颈动脉行冠状动脉造影检查,根据TIMI血流分级,实验组将TIMI分级2~3级设为慢性缺血组,TIMI分级0~1级设为梗死组;再次开胸在缺血区域进行PAT成像,计算灰度值和总量。成像后取心脏行HE染色。结果成功建立梗死组4只,慢性缺血组3只。梗死组血清心肌损伤标志物高于慢性缺血组和对照组(P0.05)。PAT总量与TIMI血流分级具有很高的等级相关性(r:0.849;P0.05)。结论Ameroid缩窄器可以用于建立慢性心肌缺血兔动物模型。而PAT对于慢性心肌缺血的评估,具有很好的应用价值。总结:应用PAT检测心肌缺血和再灌注具有很大的潜力。虽然当前研究尚有许多不足,但是随着技术的改进,PAT将在未来临床应用中发挥自己的特色。
[Abstract]:Background and objective: myocardial ischemia and reperfusion is very important in the development of cardiovascular disease. There are advantages and disadvantages in the assessment of myocardial perfusion, but they are not fully satisfied with the clinical requirements. Photoacoustic imaging technology (PAT) combines the advantages of optical and ultrasound with high resolution. In this study, three animal models of acute myocardial ischemia, acute myocardial ischemia reperfusion and chronic myocardial ischemia were established on the basis of New Zealand white rabbits on the original basis. The PAT system with faster imaging speed and higher resolution was used as the hemoglobin. Natural "contrast agent", PAT three-dimensional imaging on the rabbit's living heart was performed to evaluate the feasibility of evaluating myocardial ischemia and reperfusion..1. acute myocardial ischemia photoacoustic imaging method was randomly divided into two groups of 42 New Zealand white rabbits (2.78 + 0.23Kg): acute ischemia group directly ligated left circumflex to establish acute myocardial ischemia model and set up ligation respectively. 0.5h, 1H, 2h, 3h, 4h, 6h model, 6 only at each time point; the other 6 only thread without knot and set up the false operation 6h as the control group. The electrocardiogram was traced at different time points, the serum myocardial damage markers (C Tn I, CK-MB) were detected by blood sampling, and the PAT imaging was carried out in the ischemic region. Test and calculate the pathological indexes (semi quantitative score SAS, apoptosis index AI). Results the serum myocardial damage markers in the acute ischemic group increased with the prolongation of the ligation time (P0.05), while the AI value of the ligation group was lower than the ligation 4H group (P0.05).PAT index (gray value, total amount) decreased with the prolongation of ligation time (P0.0) (P0.0). 5).PAT index was negatively correlated with serum myocardial damage markers and pathological indexes (P0.05). Conclusion myocardial ischemia injury increased with time in 6h of acute myocardial ischemia, and the gray value, the total amount of.PAT decreased with time, could be used to evaluate the extent and extent of acute myocardial ischemia, and the gray value and total amount were in inverse proportion to myocardial ischemia injury,.2. The acute myocardial ischemia reperfusion photoacoustic imaging method divided 24 New Zealand white rabbits (2.77 0.24Kg) into reperfusion group. After ligating the left circumflex 2h, the model of acute myocardial ischemia reperfusion was set up. The models were randomly divided into 4 groups, each group was 6, and the open 0.5h, 1H, 2h, 4H reperfusion model were set up respectively. Serum myocardial damage markers were detected by blood sampling, and PAT imaging was performed in the ischemic region to calculate the gray value and total amount. After the experiment, the heart was stained with HE, TUNEL apoptosis detection and histopathology, and the technical pathological indexes were compared with those of the acute ischemia group, which were ligated to 3h, 4h, 6h and so on. The 2H group was ligated and the sham operation 6h group was taken as the pair. Results the serum myocardial damage markers and pathological indexes increased with the opening time (P0.05), except that the AI value of the open 4H group was less than the open 2H group (P0.05), but the serum myocardial damage markers and SAS in the open 4H group were lower than those of the ligation group (P0.05), while the AI 4H group AI was higher than the ligation of the 6h group. The opening time was increased (P0.05), but there was no difference between the open 4H group and the control group (P0.05), the total amount of the open 4H group was lower than the control group (P0.05).PAT index and the serum myocardial damage markers, and the pathological indexes were positively correlated (P0.05). Conclusion the myocardial injury aggravated with the increase of reperfusion time, but the aggravation of the myocardial injury was aggravated, but the aggravation of the myocardial injury was aggravated. The amplitude was less than that in the acute ischemic group; the PAT gray value and total amount were proportional to the myocardial injury; the total amount of the open 4H group did not recover to the control level. It may be related to the non reflux phenomenon that.PAT could be used to evaluate the degree of acute myocardial ischemia and reperfusion and the range of.3. chronic myocardial ischemia by the 13 New Zealand white rabbits (2.60 + 0.20Kg). The experimental group was divided into two groups. In the experimental group, 10 left circumflex Ameroid coarctation apparatus were set up to establish the chronic myocardial ischemia model, and 3 rats in the control group were taken only to open the chest and do not place the Ameroid coarctation apparatus. After modeling, the blood samples were detected for Fifth weeks, and the coronary angiography was performed by the right carotid artery, and the experimental group was graded TIMI according to the TIMI blood flow classification, and the experimental group classified TIMI 2~3 class In the chronic ischemia group, the TIMI grade 0~1 grade was set as the infarction group; the PAT imaging was performed in the ischemic area again, and the gray value and the total amount were calculated. After the imaging, the heart was stained with HE. The results were successfully established in 4 infarct groups and 3 in the chronic ischemia group. The markers of serum myocardial injury in the infarction group were higher than that of the chronic ischemia group and the control group (P0.05).PAT total and TIMI. The classification of blood flow has a high level of correlation (r:0.849; P0.05). Conclusion Ameroid coarctation can be used to establish a rabbit model of chronic myocardial ischemia. And PAT has a good application value for the assessment of chronic myocardial ischemia. Conclusion: the application of PAT to detect myocardial ischemia and reperfusion has great potential. Although there are many current studies, there are many studies. Insufficient, but with the improvement of technology, PAT will play its own characteristics in the future clinical application.

【学位授予单位】：福建医科大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R54

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