Study On Vulnerability Of Abdominal Aortic Atherosclerotic Plaque In Rabbits By Contrast-enhanced Ultrasound And Ultramicro-flow Imaging

Objective:To establish a rabbit model of abdominal aortic atherosclerosis plaque,and to detect the neovascularization in the atherosclerotic plaque of abdominal aorta by contrast-enhanced ultrasound(CEUS)and superb microvascular imaging(SMI),and to compare the difference of neovascularization in atherosclerotic plaque of abdominal aorta between different pathological groups.To compare the consistency of contrast-enhanced ultrasound and ultramicro-flow imaging in detecting vulnerability of atherosclerotic plaques in abdominal aorta of rabbits.To summarize the feasibility of plaque vulnerability assessment by contrast-enhanced ultrasound and ultramicro-flow imaging,and to do preliminary research work for widespread clinical applieation of this technology.Methods:The atherosclerotic plaque model of abdominal aorta was established in 60 New Zealand white rabbits.The blood lipid indexes of the rabbits were analyzed before and after feeding.The plaque was detected by contrast-enhanced ultrasound and ultramicro-flow imaging,and the enhancement of the plaque was observed and recorded.PS software was used to calculate the ratio of enhancement signal to plaque area,and score according to scoring criteria and statistical analysis.The plaque specimens were stained with hematoxylin-eosin(HE)and oil red 0 to observe the morphology and internal components of the plaque.The plaque was divided into vulnerable group and stable group according to pathological classification.CD34 immunohistochemical staining was used to detect neovascularization and its density in abdominal aortic atherosclerotic plaques.With pathological grouping as the gold standard,ROC curves were drawn with the scoring values of CEUS and SMI respectively,and the optimal threshold values of CEUS and SMI for judging Plaque vulnerability were obtained.The correlation between the scoring values of CEUS and SMI and microvessel density was analyzed.Time-intensity curves(TIC)of TOMTEC software were used to analyze the maximum peak intensity ratio(Imax),peak time(TPI)and average transit time(mTT)of plaque imaging.Results:1.Animal Survival:Twelve of 60 New Zealand white rabbits died and 48 survived,with a survival rate of 80%.2.Pathological classification and number of plaques:A total of 61 plaques were detected in 48 rabbits,with thickness of 0.5 mm to 1.5 mm.Pathological examination showed that there were 17 plaques in vulnerable group and 44 plaques in stable group.Among them,there are 15 plaques of type,118 plaques of type ?,11 plaques of type ?,9 plaques of type IV and 8 plaques af type V.3.Changes of plasma lipid before and after feeding:There were significant differences in blood lipid indexes(TC5 Tq LDL-C)before and after feeding for 5 months(P<0.05).4.Contrast-enhanced ultrasound and ultramicro-flow imaging were used to detect the enhancement intensity of ?-? plaque.The enhancement intensity gradually increased from type ? to type ?.Pathological classification was positively correlated with enhancement intensity.The correlation coefficients(rs)of the two techniques were 0.778 and 0.734,respectively.5.The results of consistency analysis between CEUS and Ultrasound Flow Imaging:Kappa=0.764>0.75,indicating that CEUS and Ultrasound Flow Imaging have fairly satisfactory consistency in displaying neovascularization in plaques.6.Quantitative analysis of plaque by contrast-enhanced ultrasound:The maximum peak intensity ratio(Imax),peak arrival time(TPI)and average transit time(mTT)of plaque were significantly different between vulnerable group and stable group(P<0.05).The peak arrival time and average transit time of vulnerable group were shorter than stable group,and the maximum peak intensity ratio was higher than stable group.7.Pathological examination showed that the density of neovascularization in the vulnerable group was significantly higher than that in the stable group determined by ultrasound(P<0.05).There was a significant correlation between the peak intensity ratio of plaque angiography and the microvessel density in the plaque(R=0.79,P<0.001).The greater the peak intensity ratio of plaque angiography,the greater the density of neovascularization in the plaque.8.The correlation between contrast-enhanced ultrasound(CEUS)and ultramicro-flow enhancement score(UFR)of 61 rabbit abdominal aortic plaques and plaque neovascularization density was analyzed.The results showed that the higher the score,the greater the neovascularization density.The correlation coefficients R were 0.819 and 0.750,respectively.9.With pathological grouping as the golden standard,the ROC curve was drawn by contrast-enhanced ultrasound and ultramicro-flow imaging respectively.The results showed that the optimal threshold for diagnosing vulnerable plaques was 11.5 points.At this tirue,the area under the ROC curve was 0.964,the sensitivity was 88.2%,and the specificity was 93.2%.Ultrasound flow imaging was used to diagnose vulnerable plaques with an optimal threshold of 11*5 points.The area under the ROC curve was 0.961,the sensitivity was 82.4%,and the specificity was 95.5%.Conclusion:1.Contrast-enhanced ultrasound and ultramicro-flow imaging are reliable methods to detect plaque vulnerability.The more plaque enhancement,the more neovascularization in the plaque.The more neovascularization in the plaque,the worse the stability of the plaque.2.Contrast-enhanced ultrasonography can quantitatively evaluate the enhancement of plaques,and quantitatively measure the maximum peak intensity ratio(lmax),peak time(TPI)and mean transit time(mTT)of plaques in dififerent pathological groups.The greater the peak intensity ratio of plaque contrast-enhanced ultrasound,the more neovascularization in plaque.3.With pathological grouping as the gold standard,ROC curves were drawn by using contrast-enhanced ultrasound and ultramicro-flow imaging techniques respectively.The results showed that the optimal threshold score for diagnosing vulnerable plaques was 11.5 points for both contrast-enhanced ultrasound and ultramicro-flow,but the sensitivity of contrast-enhanced ultrasound was stronger than that of ultramicro-flow,and the specificity of ultramicro-flow was stronger than that of contrast-enhanced ultrasound.Vulnerability is the best choice.