超声造影评价动脉粥样硬化斑块显像强度与新生血管密度的关系及其影响因素的研究
|
摘要
第一部分
超声造影定量评价动脉粥样硬化斑块新生血管及其与组织病理学相关性研究
目的：应用超声造影技术定量评价动脉粥样硬化斑块显像强度及其与病理染色所示的微血管密度的相关性。
方法：新西兰白兔25只球囊扩张+高脂喂养至16周后行常规超声检查观察斑块类型,以右肾动脉为参考,记录每个斑块距离右肾动脉的长度,以便取病理标本时可以精确定位。经耳缘静脉团注Sovovue0.4ml行基础超声造影检查,肉眼观察斑块有无增强,将图像导入EchoPAC工作站手动勾画斑块的边缘轮廓以构建感兴趣区,同时取管腔为对比,应用仪器中所附的时间强度曲线分析软件定量分析注射超声造影剂后的回声增强强度,曲线拟和,获取斑块注射造影剂微泡后超声增强强度A值(曲线拟合后平台期强度与基础强度之差)及其与管腔内增强强度的比值,以此定量表示注射超声造影剂后斑块超声反射回声增强强度,比较软斑与硬斑增强程度的差异。所有检查结束后过量麻醉后处死,分离腹主动脉及右肾动脉,并依据斑块在二维超声上距离右肾动脉的长度定位斑块并取材固定,CD31染色观察斑块内新生血管的密度。
结果：二维超声诊断为软斑的斑块其造影增强强度明显高于硬斑；病理检查发现超声判定为软斑的斑块经CD31染色后新生血管数目明显多于超声判定为硬斑的斑块,斑块内微血管的密度与斑块造影增强强度存在明显的相关性(R=0.75,P<0.001),与斑块增强强度/管腔增强强度亦存在明显相关性(R=0.68,P<0.001)。
结论：超声造影可以定量评价斑块的增强情况,定量测量得到的斑块增强强度与斑块内新生血管的密度具有良好的相关性,进而为定量评价斑块内微血管的密度提供了一个可靠的方法。
第二部分
血管活性物质对超声造影定量评价动脉粥样硬化斑块新生血管显像强度的影响
目的：应用超声造影技术定量评价动脉粥样硬化斑块显像强度其与血管活性物质的关系。
方法：新西兰白兔25只采用球囊扩张+高脂喂养至16周后行常规超声检查观察斑块类型。经耳缘静脉团注Sovovue0.4ml行基础超声造影检查,肉眼观察斑块有无增强,将图像导入EchoPAC工作站手动勾画斑块的边缘轮廓以构建感兴趣区,同时取管腔为对比,应用仪器中所附的时间强度曲线分析软件定量分析注射超声造影剂后的回声增强强度,曲线拟和,获取斑块注射造影剂微泡后超声增强强度A值(曲线拟合后平台期强度与基础强度之差)及其与管腔内增强强度的比值,以此定量表示注射超声造影剂后斑块超声反射回声增强强度,比较软斑与硬斑增强程度的差异。血压及心率恢复正常且造影剂完全消退后分别滴注去甲肾上腺素、三磷酸腺苷后行超声造影检查,重复观测动脉粥样硬化(AS)斑块的增强情况。采用SPSS15.0软件,所有计量资料以均数±标准差表示,以P<0.05为差异有统计学意义。软斑与硬斑造影强度的比较采用非配对T检验。滴注去甲肾上腺素及三磷酸腺苷后斑块增强强度、增强强度与管腔比值与基础造影的比较采用配对T检验。
结果：经二维超声检查共发现可用斑块63个,其中经超声检查判定为软斑50个,硬斑13个。滴注去甲肾上腺素后2个斑块显像欠佳而剔除,滴注三磷酸腺苷后1个斑块显像欠佳而剔除。二维超声诊断为硬斑的斑块其造影增强强度明显低于软斑(5.76±2.31vs7.97±2.63,P=0.008)；在滴注去甲肾上腺素后斑块造影增强强度及其与管腔增强强度比值均低于基础状态下的增强强度(6.41±2.90vs7.51±3.81,P<0.001；0.38±0.17vs0.45±0.16,P=0.002),而滴注三磷酸腺苷后斑块增强强度其与管腔增强强度比值均高于基础增强强度(9.78±3.54vs7.49±2.72,P<0.001；0.59±0.23vs0.46±0.17,P<0.001)。
结论：血管活性物质可影响斑块新生血管的显像强度,超声造影可以定量评估AS斑块新生血管显像强度及血管活性物质对其影响,进而可以更为全面的评价AS斑块的稳定性。
第三部分
超声造影定量评价动脉粥样硬化斑块新生血管显像强度及内皮活性物质的影响
目的：应用超声造影技术定量评价动脉粥样硬化斑块显像强度其与血管内皮状态的关系。
方法：新西兰白兔25只采用球囊扩张+高脂喂养至16周后行常规超声检查观察斑块类型。经耳缘静脉团注Sonovue0.4ml行基础超声造影检查,肉眼观察斑块有无增强,将图像导入EchoPAC工作站手动勾画斑块的边缘轮廓以构建感兴趣区,同时取管腔为对比,应用仪器中所附的时间强度曲线分析软件定量分析注射超声造影剂后的回声增强强度,曲线拟和,获取斑块注射造影剂微泡后超声增强强度A值(曲线拟合后平台期强度与基础强度之差)及其与管腔内增强强度的比值,以此定量表示注射超声造影剂后斑块超声反射回声增强强度,比较软斑与硬斑增强程度的差异。血压及心率恢复正常且造影剂完全消退后分别滴注单甲基精氨酸(LNMMA)、内皮受体阻滞剂(PD142893)后行超声造影检查,重复观测动脉粥样硬化(AS)斑块的增强情况。采用SPSS15.0软件,所有计量资料以均数±标准差表示,以P<0.05为差异有统计学意义。软斑与硬斑造影强度的比较采用独立样本T检验。滴注LNMMA及PD142893后斑块增强强度、增强强度与管腔比值与基础造影的比较采用配对T检验。
结果：经二维超声检查共发现可用斑块63个,其中经超声检查判定为软斑50个,硬斑13个。63个斑块滴注LNMMA及PD142893后由于各种显像原因导致分别有16个,9个斑块被剔除。二维超声诊断为硬斑的斑块其造影增强强度明显低于软斑(5.76±2.31dB vs7.97±2.63dB, P=0.008);在滴注LNMMA后斑块造影增强强度及其与管腔增强强度比值均低于基础状态下造影的增强强度(5.48±1.57dB vs7.04±2.26dB,P<0.001；0.40±0.13vs0.46±0.17,P=0.003),在滴注PD142893后斑块造影增强强度及其与管腔增强强度比值均高于基础状态下造影的增强强度(8.31±3.29dB vs7.41±2.85dB,P=0.018；0.51±0.22vs0.45±0.17,P=0.012)。
结论：内皮活性物质的浓度影响斑块的显像强度,超声造影可以定量评估AS斑块新生血管显像强度及其受内皮收缩或舒张的影响程度,进而可以更为全面的评价AS斑块的稳定性。
PartⅠ
Correlation of enhanced intensity of atherosclerotic plaque at contrast-enhanced ultrasonography with histological findings
Objectives:To evaluate the relationship between plaque neovascularization and plaque enhanced intensity by contrast-enhanced ultrasonography.
Methods:25New Zealand white rabbits were fed with high fat diet to16weeks. CEU was performed to observe plaque echogenicity. Time-intensity curve was used to quantify the El of plaques. After harvesting the aorta, CD31stain was performed for calculating the density of neovascularization.
Results:The echolucent plaques had higher E during CEU and higher neovascularization density at pathological stain than the echogenic plaques.The atherosclerotic plaque El and its ratio to luminal El were well related with neovascularization density (R=0.75, P<0.001; R=0.68, P<0.001) respectively.
Conclusions:The atherosclerotic plaque enhanced intensity during CEU was well correlated to neovascularization density.CEU can assess the enhanced intensity of atherosclerotic plaque quantitatively, thus providing us a reliable way for evaluating the neovascularization of atherosclerotic plaque.
Part Ⅱ
The Evaluation of Effects of Vasoactive Substances on Plaque Enhanced Intensity during Contrast-Enhanced Ultrasonography
Objects:To evaluate the effects of vasoactive substances on plaque enhanced intensity during contrast-enhanced ultrasonography.
Method:25New Zealand white rabbits were fed with a high fat and cholesterol diet for16weeks following balloon injury. Routine ultrasonic examinations were performed to classify the plaques into echolucent or echogenic according to their echogenicities. Rabbits were intravenously administered a0.4mL Sonovue bolus to perform the contrast examination. The images were stored in EchoPAC work station. Enhanced intensity in each frame was measured in the plaque drawn as a region of interest. Curve fitting was done with the formula Y(t)=A(1-e-kt)+B to get the enhanced intensity of the plaques and the lumen by computing the variation of plateau intensity and initial intensity. The enhanced intensity was then compared between the echolucent and the echogenic plaques. The rabbits were later injected with noradrenalin (NA), triphosadenine(ATP) respectively after the heart rate and blood pressure recovered, and repeat examination was done with contrast agent and enhanced intensity of the plaque was quantified again. SPSS15.0software was used to calculate the statistical characteristics of the data. All the measured data were displayed as mean±standard deviation. P<0.05was defined as having statistical significant difference. Independent sample T test was applied to analyze the variation between echolucent and echogenic plaques. The variation of enhanced intensity at baseline and after injecting NA or ATP was analyzed by paired T test.
Results:The echolucent plaques expressed higher enhanced intensity than echogenic plaques (7.97±2.63dB vs.5.76±2.31dB, P=0.008). After administration of NA, plaque enhanced intensity and its ratio to lumen were lower than the base values (6.41±2.90vs7.51±3.81, P<0.001;0.38±0.17vs0.45±0.16,P=0.002) whereas the intensity and its ration to lumen after injecting ATP were higher than baseline(9.78±3.54vs7.49±2.72, P<0.001;0.59±0.23vs0.46±0.17, P<0.001).
Conclusion:The enhanced intensity of the plaque can be affected by vasoactive substances. CEU may be useful to quantify the enhanced intensity of the plaque and the degree by which it is affected by vasoactive substances. It would then play an important role in evaluating the stability of atherosclerotic plaque.
Part III
The Evaluation of effects of Endothelial Active Substances on Plaque Enhanced Intensity during Contrast-Enhanced Ultrasonography
Objects:To evaluate the effects of endothelial active substances on plaque enhanced intensity during contrast-enhanced ultrasonography.
Method:25New Zealand white rabbits were fed with a high fat and cholesterol diet for16weeks following balloon injury. Routine ultrasonic examination was performed to classify the plaques into echolucent or echogenic according to their echogenicities. Rabbits were intravenously administered a0.4mL Sonovue bolus to perform the contrast examination. The images were stored in EchoPAC work station. Enhanced intensity in each frame was measured in the plaque drawn as a region of interest. Curve fitting was done with the formula Y(t)=A(1-e-kt)+B to get the enhanced intensity of the plaques and the lumen by computing the variation of plateau intensity and initial intensity. The enhanced intensity was then compared between the echolucent and the echogenic plaques. The rabbits were later injected with Methyl Arginine (LNMMA) and endothelial blockers (PD142893) respectively when the heart rate and blood pressure recovered, and repeat examination was done with contrast agent and enhanced intensity of the plaque was quantified again. SPSS15.0software was used to calculate the statistical characteristics of the data. All the measured data were displayed as mean±standard deviation. P<0.05was defined as having statistical significant difference. Independent sample T test was applied to analyze the variation between echolucent and echogenic plaques. The variation of enhanced intensity at baseline and after injecting LNMMA or PD142893was analyzed by paired T test.
Results:The echolucent plaques expressed higher enhanced intensity than echogenic plaques (7.97±2.63dB vs.5.76±2.31dB,P=0.008). After administration of LNMMA, plaque enhanced intensity and its ratio to lumen were lower than the base values (5.48±1.57dB vs7.04±2.26dB,P<0.001;0.40±0.13vs0.46±0.17, P=0.003) whereas the intensity and its ratio to lumen was higher after injecting PD142893(8.31±3.29dB vs7.41±2.85dB, P=0.018;0.51±0.22vs0.45±0.17, P=0.012).
Conclusion:The enhanced intensity of the plaque can be affected by endothelial active substances. CEU may be useful to quantify the enhanced intensity of the plaque and the degree by which it is affected by endothelial active substances. It would then play an important role in evaluating the stability of atherosclerotic plaque.
超声造影定量评价动脉粥样硬化斑块新生血管及其与组织病理学相关性研究
目的：应用超声造影技术定量评价动脉粥样硬化斑块显像强度及其与病理染色所示的微血管密度的相关性。
方法：新西兰白兔25只球囊扩张+高脂喂养至16周后行常规超声检查观察斑块类型,以右肾动脉为参考,记录每个斑块距离右肾动脉的长度,以便取病理标本时可以精确定位。经耳缘静脉团注Sovovue0.4ml行基础超声造影检查,肉眼观察斑块有无增强,将图像导入EchoPAC工作站手动勾画斑块的边缘轮廓以构建感兴趣区,同时取管腔为对比,应用仪器中所附的时间强度曲线分析软件定量分析注射超声造影剂后的回声增强强度,曲线拟和,获取斑块注射造影剂微泡后超声增强强度A值(曲线拟合后平台期强度与基础强度之差)及其与管腔内增强强度的比值,以此定量表示注射超声造影剂后斑块超声反射回声增强强度,比较软斑与硬斑增强程度的差异。所有检查结束后过量麻醉后处死,分离腹主动脉及右肾动脉,并依据斑块在二维超声上距离右肾动脉的长度定位斑块并取材固定,CD31染色观察斑块内新生血管的密度。
结果：二维超声诊断为软斑的斑块其造影增强强度明显高于硬斑；病理检查发现超声判定为软斑的斑块经CD31染色后新生血管数目明显多于超声判定为硬斑的斑块,斑块内微血管的密度与斑块造影增强强度存在明显的相关性(R=0.75,P<0.001),与斑块增强强度/管腔增强强度亦存在明显相关性(R=0.68,P<0.001)。
结论：超声造影可以定量评价斑块的增强情况,定量测量得到的斑块增强强度与斑块内新生血管的密度具有良好的相关性,进而为定量评价斑块内微血管的密度提供了一个可靠的方法。
第二部分
血管活性物质对超声造影定量评价动脉粥样硬化斑块新生血管显像强度的影响
目的：应用超声造影技术定量评价动脉粥样硬化斑块显像强度其与血管活性物质的关系。
方法：新西兰白兔25只采用球囊扩张+高脂喂养至16周后行常规超声检查观察斑块类型。经耳缘静脉团注Sovovue0.4ml行基础超声造影检查,肉眼观察斑块有无增强,将图像导入EchoPAC工作站手动勾画斑块的边缘轮廓以构建感兴趣区,同时取管腔为对比,应用仪器中所附的时间强度曲线分析软件定量分析注射超声造影剂后的回声增强强度,曲线拟和,获取斑块注射造影剂微泡后超声增强强度A值(曲线拟合后平台期强度与基础强度之差)及其与管腔内增强强度的比值,以此定量表示注射超声造影剂后斑块超声反射回声增强强度,比较软斑与硬斑增强程度的差异。血压及心率恢复正常且造影剂完全消退后分别滴注去甲肾上腺素、三磷酸腺苷后行超声造影检查,重复观测动脉粥样硬化(AS)斑块的增强情况。采用SPSS15.0软件,所有计量资料以均数±标准差表示,以P<0.05为差异有统计学意义。软斑与硬斑造影强度的比较采用非配对T检验。滴注去甲肾上腺素及三磷酸腺苷后斑块增强强度、增强强度与管腔比值与基础造影的比较采用配对T检验。
结果：经二维超声检查共发现可用斑块63个,其中经超声检查判定为软斑50个,硬斑13个。滴注去甲肾上腺素后2个斑块显像欠佳而剔除,滴注三磷酸腺苷后1个斑块显像欠佳而剔除。二维超声诊断为硬斑的斑块其造影增强强度明显低于软斑(5.76±2.31vs7.97±2.63,P=0.008)；在滴注去甲肾上腺素后斑块造影增强强度及其与管腔增强强度比值均低于基础状态下的增强强度(6.41±2.90vs7.51±3.81,P<0.001；0.38±0.17vs0.45±0.16,P=0.002),而滴注三磷酸腺苷后斑块增强强度其与管腔增强强度比值均高于基础增强强度(9.78±3.54vs7.49±2.72,P<0.001；0.59±0.23vs0.46±0.17,P<0.001)。
结论：血管活性物质可影响斑块新生血管的显像强度,超声造影可以定量评估AS斑块新生血管显像强度及血管活性物质对其影响,进而可以更为全面的评价AS斑块的稳定性。
第三部分
超声造影定量评价动脉粥样硬化斑块新生血管显像强度及内皮活性物质的影响
目的：应用超声造影技术定量评价动脉粥样硬化斑块显像强度其与血管内皮状态的关系。
方法：新西兰白兔25只采用球囊扩张+高脂喂养至16周后行常规超声检查观察斑块类型。经耳缘静脉团注Sonovue0.4ml行基础超声造影检查,肉眼观察斑块有无增强,将图像导入EchoPAC工作站手动勾画斑块的边缘轮廓以构建感兴趣区,同时取管腔为对比,应用仪器中所附的时间强度曲线分析软件定量分析注射超声造影剂后的回声增强强度,曲线拟和,获取斑块注射造影剂微泡后超声增强强度A值(曲线拟合后平台期强度与基础强度之差)及其与管腔内增强强度的比值,以此定量表示注射超声造影剂后斑块超声反射回声增强强度,比较软斑与硬斑增强程度的差异。血压及心率恢复正常且造影剂完全消退后分别滴注单甲基精氨酸(LNMMA)、内皮受体阻滞剂(PD142893)后行超声造影检查,重复观测动脉粥样硬化(AS)斑块的增强情况。采用SPSS15.0软件,所有计量资料以均数±标准差表示,以P<0.05为差异有统计学意义。软斑与硬斑造影强度的比较采用独立样本T检验。滴注LNMMA及PD142893后斑块增强强度、增强强度与管腔比值与基础造影的比较采用配对T检验。
结果：经二维超声检查共发现可用斑块63个,其中经超声检查判定为软斑50个,硬斑13个。63个斑块滴注LNMMA及PD142893后由于各种显像原因导致分别有16个,9个斑块被剔除。二维超声诊断为硬斑的斑块其造影增强强度明显低于软斑(5.76±2.31dB vs7.97±2.63dB, P=0.008);在滴注LNMMA后斑块造影增强强度及其与管腔增强强度比值均低于基础状态下造影的增强强度(5.48±1.57dB vs7.04±2.26dB,P<0.001；0.40±0.13vs0.46±0.17,P=0.003),在滴注PD142893后斑块造影增强强度及其与管腔增强强度比值均高于基础状态下造影的增强强度(8.31±3.29dB vs7.41±2.85dB,P=0.018；0.51±0.22vs0.45±0.17,P=0.012)。
结论：内皮活性物质的浓度影响斑块的显像强度,超声造影可以定量评估AS斑块新生血管显像强度及其受内皮收缩或舒张的影响程度,进而可以更为全面的评价AS斑块的稳定性。
PartⅠ
Correlation of enhanced intensity of atherosclerotic plaque at contrast-enhanced ultrasonography with histological findings
Objectives:To evaluate the relationship between plaque neovascularization and plaque enhanced intensity by contrast-enhanced ultrasonography.
Methods:25New Zealand white rabbits were fed with high fat diet to16weeks. CEU was performed to observe plaque echogenicity. Time-intensity curve was used to quantify the El of plaques. After harvesting the aorta, CD31stain was performed for calculating the density of neovascularization.
Results:The echolucent plaques had higher E during CEU and higher neovascularization density at pathological stain than the echogenic plaques.The atherosclerotic plaque El and its ratio to luminal El were well related with neovascularization density (R=0.75, P<0.001; R=0.68, P<0.001) respectively.
Conclusions:The atherosclerotic plaque enhanced intensity during CEU was well correlated to neovascularization density.CEU can assess the enhanced intensity of atherosclerotic plaque quantitatively, thus providing us a reliable way for evaluating the neovascularization of atherosclerotic plaque.
Part Ⅱ
The Evaluation of Effects of Vasoactive Substances on Plaque Enhanced Intensity during Contrast-Enhanced Ultrasonography
Objects:To evaluate the effects of vasoactive substances on plaque enhanced intensity during contrast-enhanced ultrasonography.
Method:25New Zealand white rabbits were fed with a high fat and cholesterol diet for16weeks following balloon injury. Routine ultrasonic examinations were performed to classify the plaques into echolucent or echogenic according to their echogenicities. Rabbits were intravenously administered a0.4mL Sonovue bolus to perform the contrast examination. The images were stored in EchoPAC work station. Enhanced intensity in each frame was measured in the plaque drawn as a region of interest. Curve fitting was done with the formula Y(t)=A(1-e-kt)+B to get the enhanced intensity of the plaques and the lumen by computing the variation of plateau intensity and initial intensity. The enhanced intensity was then compared between the echolucent and the echogenic plaques. The rabbits were later injected with noradrenalin (NA), triphosadenine(ATP) respectively after the heart rate and blood pressure recovered, and repeat examination was done with contrast agent and enhanced intensity of the plaque was quantified again. SPSS15.0software was used to calculate the statistical characteristics of the data. All the measured data were displayed as mean±standard deviation. P<0.05was defined as having statistical significant difference. Independent sample T test was applied to analyze the variation between echolucent and echogenic plaques. The variation of enhanced intensity at baseline and after injecting NA or ATP was analyzed by paired T test.
Results:The echolucent plaques expressed higher enhanced intensity than echogenic plaques (7.97±2.63dB vs.5.76±2.31dB, P=0.008). After administration of NA, plaque enhanced intensity and its ratio to lumen were lower than the base values (6.41±2.90vs7.51±3.81, P<0.001;0.38±0.17vs0.45±0.16,P=0.002) whereas the intensity and its ration to lumen after injecting ATP were higher than baseline(9.78±3.54vs7.49±2.72, P<0.001;0.59±0.23vs0.46±0.17, P<0.001).
Conclusion:The enhanced intensity of the plaque can be affected by vasoactive substances. CEU may be useful to quantify the enhanced intensity of the plaque and the degree by which it is affected by vasoactive substances. It would then play an important role in evaluating the stability of atherosclerotic plaque.
Part III
The Evaluation of effects of Endothelial Active Substances on Plaque Enhanced Intensity during Contrast-Enhanced Ultrasonography
Objects:To evaluate the effects of endothelial active substances on plaque enhanced intensity during contrast-enhanced ultrasonography.
Method:25New Zealand white rabbits were fed with a high fat and cholesterol diet for16weeks following balloon injury. Routine ultrasonic examination was performed to classify the plaques into echolucent or echogenic according to their echogenicities. Rabbits were intravenously administered a0.4mL Sonovue bolus to perform the contrast examination. The images were stored in EchoPAC work station. Enhanced intensity in each frame was measured in the plaque drawn as a region of interest. Curve fitting was done with the formula Y(t)=A(1-e-kt)+B to get the enhanced intensity of the plaques and the lumen by computing the variation of plateau intensity and initial intensity. The enhanced intensity was then compared between the echolucent and the echogenic plaques. The rabbits were later injected with Methyl Arginine (LNMMA) and endothelial blockers (PD142893) respectively when the heart rate and blood pressure recovered, and repeat examination was done with contrast agent and enhanced intensity of the plaque was quantified again. SPSS15.0software was used to calculate the statistical characteristics of the data. All the measured data were displayed as mean±standard deviation. P<0.05was defined as having statistical significant difference. Independent sample T test was applied to analyze the variation between echolucent and echogenic plaques. The variation of enhanced intensity at baseline and after injecting LNMMA or PD142893was analyzed by paired T test.
Results:The echolucent plaques expressed higher enhanced intensity than echogenic plaques (7.97±2.63dB vs.5.76±2.31dB,P=0.008). After administration of LNMMA, plaque enhanced intensity and its ratio to lumen were lower than the base values (5.48±1.57dB vs7.04±2.26dB,P<0.001;0.40±0.13vs0.46±0.17, P=0.003) whereas the intensity and its ratio to lumen was higher after injecting PD142893(8.31±3.29dB vs7.41±2.85dB, P=0.018;0.51±0.22vs0.45±0.17, P=0.012).
Conclusion:The enhanced intensity of the plaque can be affected by endothelial active substances. CEU may be useful to quantify the enhanced intensity of the plaque and the degree by which it is affected by endothelial active substances. It would then play an important role in evaluating the stability of atherosclerotic plaque.
引文
1 Casscells W, Naghavi M, Willerson JT. Vulnerable atherosclerotic plaque:a multifocal disease. Circulation,2003,107(16):2072-2075.
2 Virmani R, Burke AP, Farb A, et al. Pathology of the Vulnerable Plaque. J Am Coll Cardiol,2006,47(8):13-18.
3 Macura KJ, Corl FM, Fishman EK, et al. Pathogenesis in acute aortic syndromes:aortic dissection, intramural hematoma, and penetrating atherosclerotic aortic ulcer. AJR Am J Roentgenol,2003,181 (2):309-316.
4 Wolinsky H, Glagov S. Nature of species differences in the medial distribution of aortic vasa vasorum in mammals. Circ Res,1967,20 (4):409-421.
5 Heistad DD, Armstrong ML, Amundsen S. Blood flow through vasa vasorum in arteries and veins:effects of luminal PO2. Am J Physiol,1986,250 (3 Pt 2):H434-442.
6 Herbst WM, Eberle KP, Ozen Y, et al. The innervation of the great saphenous vein:an immunohistochemical study with special regard to regulatory peptides. Vasa,1992,21 (3):253-257.
7 Ritm an LE, Lerman A. Role of vasa vasorum in arterial disease:a re-emerging factor. Curr Cardiol Rev,2007,3 (1):43- 55.
8 Scotlan d RS, Vallance PJT, Ahlu walia A. Endogenous factors involved in regulation of tone of arterial vasa vasorum:implications for conduit vessel physiology. Cardiovasc Res,2000,46(3):403-411.
9 Ohhira A, Ohhashi T. Effects of aortic pressure and vasoactive agents on the vascular resistance of the vasa vasorum in canine vessels results in vascular lesions and certain vascula r isolated thoracic aorta. J Physiol,1992,453:233-245.
10 Scotlan d RS, Vallance P, Ahluw alia A. On the regulation of tone in vasa vasorum. Cardiov asc Res,1999,41 (1):237-245.
11 Scotland R, Vallance P, Ahluwalia A. Endothelin alters the reactivity of vasa vasorum: mechanisms and implications for conduit vessel physiology and pathophysiology. Br J Pharmacol,1999,128 (6):1229-1234.
12 Carlier S, Kakadiaris IA, Dib N, et al. Vasa vasorum imaging:a new window to the clinical detection of vulnerable atherosclerotic plaques. Curr Atheroscler Rep,2005,7 (2):164-169.
13 Juan-Babot JO, Martinez-Gonzalez J, Berrozpe M, et al. Neovascularization in human coronary arteries with lesions of different severity, Rev Esp Cardiol,2003,56 (10):978-986.
14 Moreno PR, Purushothaman KR, Fuster V, et al. Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta:implications for plaque vulnerability. Circulation,2004,110 (14):2032-2038.
15 Heistad DD, Marcus ML, Larsen GE, et al. Role of vasa vasorum in nourishment of the aortic wall. Am J Physiol.1981,240 (5):H781-787.
16 Virmani R, Kolodgie FD, Burke AP, et al. Atherosclerotic plaque progression and vulnerability to rupture:angiogenesis as a source of intraplaque hemorrhage. Arterioscler Thromb Vasc Biol,2005,25 (10):2054-2061.
17 Virmani R, Kolodgie FD, Burke AP, et al. Lessons from sudden coronary death:a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol,2000,20 (5):1262-1275.
18 Fleiner M, Kummer M, Mirlacher M, et al. Arterial neovascularization and inflammation in vulnerable patients:early and late signs of symptomatic atherosclerosis. Circulation,2004,110 (18):2843-2850.
19 Feinstein SB. The powerful microbubble:from bench to bedside, from intravascular indicator to therapeutic delivery system, and beyond. Am J Physiol Heart Circ Physiol, 2004,287 (2):H450-457.
1 Hoogi A, Adam D, Hoffman A, et al. Carotid plaque vulnerability:quantification of neovascularization on contrast-enhanced ultrasound with histopathologic correlation. AJRAm J Roentgenol,2011,196,431-436.
2 Carlier S, Kakadiaris IA, Dib N, et al. Vasa vasorum imaging:a new window to the clinical detection of vulnerable atherosclerotic plaques. Curr Atheroscler Rep,2005, 7:164-169.
3 Moreno PR, Purushothaman KR, Sirol M, et al. Neovascularization in human atherosclerosis. Circulation,2006,113:2245-2252.
4 Sluimer JC, Daemen MJ. Novel concepts in atherogenesis:angiogenesis and hypoxia in atherosclerosis. J Pathol,2009,218:7-29.
5 Staub D, Schinkel AF, Coll B, et al. Contrast-enhanced ultrasound imaging of the vasa vasorum:from early atherosclerosis to the identification of unstable plaques. JACC Cardiovasc Imaging,2010,3:761-771.
6 Dunmore BJ, McCarthy MJ, Naylor AR, et al. Carotid plaque instability and ischemic symptoms are linked to immaturity of micro vessels within plaques. J Vase Surg,2007, 45:155-159.
7熊莉,邓又斌,毕小军,等.超声造影评价颈动脉粥样斑块稳定性.中华超声影像学杂志,2008,17：214-216.
8 Xiong L, Deng YB, Zhu Y, et al. Correlation of carotid plaque neovascularization detected by using contrast-enhanced US with clinical symptoms. Radiology,2009, 251(2):583-589.
9 Shalhoub J, Owen DR, Gauthier T, et al. The use of contrast enhanced ultrasound in carotid arterial disease. Eur J Vase Endovasc Surg,2010,39:381-387.
10 Staub D, Patel MB, Tibrewala A, et al. Vasa vasorum and plaque neovascularization on contrast-enhanced carotid ultrasound imaging correlates with cardiovascular disease and past cardiovascular events. Stroke,2010,41:41-47.
11 Staub D, Partovi S, Schinkel AF, et al. Correlation of carotid artery atherosclerotic lesion echogenicity and severity at standard US with intraplaque neovascularization detected at contrast-enhanced US. Radiology,2011,258:618-626.
12 Feinstein SB, Coll B, Staub D, et al. Contrast enhanced ultrasound imaging. J Nucl Cardiol 2010,17:106-115.
13 Vicenzini E, Giannoni MF, Puccinelli F, et al. Detection of carotid adventitial vasa vasorum and plaque vascularization with ultrasound cadence contrast pulse sequencing technique and echo-contrast agent. Stroke,2007,38:2841-2843.
14 Feinstein SB. The powerful microbubble:from bench to bedside, from intravascular indicator to therapeutic delivery system, and beyond. Am J Physiol Heart Circ Physiol, 2004,287:H451-H457.
15朱英,邓又斌,刘娅妮,等.超声造影成像技术评价颈动脉斑块内新生血管与斑块声学特性的关系.中华医学超声杂志(电子版),2009,5：882-886.
16 Shah F, Balan P, Weinberg M,et al. Contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization a new surrogate marker of atherosclerosis. Vasc Med,2007,12:291-297.
1 Hoogi A, Adam D, Hoffman A, et al. Carotid plaque vulnerability:quantification of neovascularization on contrast-enhanced ultrasound with histopathologic correlation. AJR Am J Roentgenol,2011,196(2):431-436.
2 Carlier S, Kakadiaris IA, Dib N, et al. Vasa vasorum imaging:a new window to the clinical detection of vulnerable atherosclerotic plaques. Curr Atheroscler Rep,2005,7 (2):164-169.
3 Heistad DD, Marcus ML, Larsen GE, et al. Role of vasa vasorum in nourishment of the aortic wall. Am J Physiol,1981,240 (5):H781-787.
4 Moreno PR, Purushothaman KR, Sirol M, et al. Neovascularization in human atherosclerosis. Circulation,2006,113 (18):2245-2252.
5 Virmani R, Kolodgie FD, Burke AP, et al. Atherosclerotic plaque progression and vulnerability to rupture:angiogenesis as a source of intraplaque hemorrhage. Arterioscler Thromb Vasc Biol,2005,25(10):2054-2061.
6 Fleiner M, Kummer M, Mirlacher M, et al. Arterial neovascularization and inflammation in vulnerable patients:early and late signs of symptomatic atherosclerosis. Circulation,2004,110 (18):2843-2850.
7 Feinstein SB. Contrast ultrasound imaging of the carotid artery vasa vasorum and atherosclerotic plaque neovascularization. J Am Coll Cardiol,2006,48 (2):236-243.
8 Xiong L, Deng YB, Zhu Y, et al. Correlation of carotid plaque neovascularization detected by using contrast-enhanced US with clinical symptoms. Radiology,2009, 251 (2):583-589.
9 Staub D, Partovi S, Schinkel AF, et al. Correlation of carotid artery atherosclerotic lesion echogenicity and severity at standard US with intraplaque neovascularization detected at contrast-enhanced US. Radiology,2011,258 (2):618-626.
10朱英,邓又斌,刘娅妮,等.超声造影成像技术评价颈动脉斑块内新生血管与斑块声学特性的关系.中华医学超声杂志(电子版),2009；6(5)：882-886.
11 Vicenzini E, Giannoni MF, Puccinelli F, et al. Detection of carotid adventitial vasa vasorum and plaque vascularization with ultrasound cadence contrast pulse sequencing technique and echo-contrast agent. Stroke,2007,38 (10):2841-2843.
12 Papaioannou TG, Vavuranakis M, Androulakis A, et al. In-vivo imaging of carotid plaque neoangiogenesis with contrast-enhanced harmonic ultrasound. Int J Cardiol, 2009,134 (3):110-112.
13 Magnoni M, Coli S, Marrocco-Trischitta MM, et al. Contrast-enhanced ultrasound imaging of periadventitial vasa vasorum in human carotid arteries. Eur J Echocardiogr, 2009,10 (2):260-264.
14 Wilens SL, Plair CM. Blood cholesterol, nutrition, therosclerosis. anecropsy study. Arch Intern Med,1965,116:373-380.
15 Ritman LE, Lerman A. Role of vasa vasorum in arterial disease:a re-emerging factor. Curr Cardiol Rev,2007,3 (1):43-55.
16 Scotland RS, Vallance PJ, Ahluwalia A. Endogenou s factors involved in regulation of tone of arterial vasa vasorum:implications for conduit vessel physiology. Cardiovasc Res,2000,46 (3):403-411.
17 Ritman EL, Lerman A. The dynamic vasa vasorum. Cardiovasc Res,2007,75 (4):649-658.
18 Ohhira A, Ohhashi T. Effects of aortic pressure and vasoactive agents on the vascular resistance of the vasa vasorum in canine vessels results in vascular lesions and certain vascular isolated thoracic aorta. J Physiol,1992,453:233-245.
19 Sacks AH. The vasa vasorum as a link between hypertension and arteriosclerosis. Angiology,1975,26:385-390.
20熊莉,邓又斌,毕小军,等.超声造影评价颈动脉粥样斑块稳定性.中华超声影像学杂志,2008,17(3)：214-216.
21杨宝峰,苏定冯主编.药理学.第6版,北京：人民卫生出版社,2004：89-93.
22 Gossl M, Rosol M, Malyar NM, et al. Functional anatomy and hemodynamic characteristics of vasa vasorum in the walls of porcine coronary arteries. Anat Rec A Discov Mol Cell Evol Biol,2003,272 (2):526-537.
23 Den Hartog JP. Strength of materials. New York:Dover Publications, Inc,1949, p323.
24 Guan Z, Inscho EW. Role of adenosine 5'-triphosphate in regulating renal microvascular function and in hypertension. Hypertension,2011,58 (3):333-340.
1 Hoogi A, Adam D, Hoffman A, et al. Carotid plaque vulnerability:quantification of neovascularization on contrast-enhanced ultrasound with histopathologic correlation. AJR Am J Roentgenol,2011,196 (2):431-436.
2 Casscells W, Naghavi M, Willerson JT. Vulnerable atherosclerotic plaque:a multifocal disease. Circulation,2003,107 (16):2072-2075.
3 Virmani R, Burke AP, Farb A,et al. Pathology of the Vulnerable Plaque. J Am Coll Cardiol,2006,47 (8):13-18.
4 Fleiner M, Kummer M, Mirlacher M, et al. Arterial neovascularization and inflammation in vulnerable patients:early and late signs of symptomatic atherosclerosis. Circulation,2004,110 (18):2843-2850.
5 Dunmore BJ, McCarthy MJ, Naylor AR, et al. Carotid plaque instability and ischemic symptoms are linked to immaturity of microvessels within plaques. J Vase Surg,2007, 45 (1):155-159.
6 Feinstein SB. Contrast ultrasound imaging of the carotid artery vasa vasorum and atherosclerotic plaque neovascularization. J Am Coll Cardiol,2006,48 (2):236-243.
7 Carlier S, Kakadiaris IA, Dib N, et al. Vasa vasorum imaging:a new window to the clinical detection of vulnerable atherosclerotic plaques. Curr Atheroscler Rep,2005,7 (2):164-169.
8 Moreno PR, Purushothaman KR, Sirol M, et al. Neovascularization in human atherosclerosis. Circulation,2006,113 (18):2245-2252.
9 Xiong L, Deng YB, Zhu Y, et al. Correlation of carotid plaque neovascularization detected by using contrast-enhanced US with clinical symptoms. Radiology,2009, 251 (2):583-589.
10 Staub D, Partovi S, Schinkel AF, et al. Correlation of carotid artery atherosclerotic lesion echogenicity and severity at standard US with intraplaque neovascularization detected at contrast-enhanced US. Radiology,2011,258 (2):618-626.
11朱英,邓又斌,刘娅妮,等.超声造影成像技术评价颈动脉斑块内新生血管与斑 块声学特性的关系.中华医学超声杂志(电子版),2009;6(5)：882-886.
12 Vicenzini E, Giannoni MF, Puccinelli F, et al. Detection of carotid adventitial vasa vasorum and plaque vascularization with ultrasound cadence contrast pulse sequencing technique and echo-contrast agent. Stroke,2007,38 (10):2841-2843.
13 Papaioannou TQ Vavuranakis M, Androulakis A, et al. In-vivo imaging of carotid plaque neoangiogenesis with contrast-enhanced harmonic ultrasound. Int J Cardiol, 2009,134(3):110-112.
14 Magnoni M, Coli S, Marrocco-Trischitta MM, et al. Contrast-enhanced ultrasound imaging of periadventitial vasa vasorum in human carotid arteries. Eur J Echocardiogr, 2009,10 (2):260-264.
15 Moguillansky D, Leng X, Carson A, et al. Quantification of plaque neovascularization using contrast ultrasound:a histologic validation. Eur Heart J,2011,32 (5):646-653.
16 Wilens SL, Plair CM. Blood cholesterol, nutrition, therosclerosis. anecropsy study. Arch Intern Med,1965,116:373-380.
17 Scotlan d RS, Vallance PJT, Ahlu walia A. Endogenou s factors involved in regulat ion of tone of arterial vasa vasorum:imp lications for conduit vesse 1 physiology. Cardiovasc Res,2000,46 (3):403- 411.
18 Heistad D, Marcus M, Martin J. Effects of neural stimulion blood through vasa vasorum in dogs. Circ Res,1979,45 (5):615-620.
19 Scotlan d RS, Vallance P, Ahluw alia A. On the regulation of tone in vasa vasorum. Cardiov asc Res,1999,41 (1):237- 245.
20 Scotland R, Vallance P, Ahluwalia A. Endothelin alters the reactivity of vasa vasorum: mechanisms and implications for conduit vessel physiology and pathophysiology. Br J Pharmacol,1999,128 (6):1229-1234.
21熊莉,邓又斌,毕小军,等.超声造影评价颈动脉粥样斑块稳定性.中华超声影像学杂志.2008,17(3)：214-216.
22 Moncada S, Palmer RM, Higgs EA. Nitric Oxide:physiology, pathophysiology, and pharmacology. Pharmacol Rev,1991,43 (2):109-142.
23 Nadaud S, Bonnardeaux A, Lathrop M, et al. Gene structure polymorphism and mapping of the human endothelial nitric oxide synthase gene. Biochem Biophys Res Commun,1994,198 (3):1027-1033.
24 Lerman A, Edwards BS, Hallett JW, et al. Circulating and tissue endothelin immunoreactivity in advanced atherosclerosis. N Engl J Med,1991,325 (14): 997-1001.
25 Winkles JA, Alberts GF, Brogi E, et al. Endothelin-1 and endothelin receptor mRNA expression in normal and atherosclerotic human arteries. Biochem Biophys Res Commun,1993,191 (3):1081-1088.
26 Haynes WG, Strachan FE, Webb DJ. Endothelin ETA and ETB receptors cause vasoconstriction of human resistance and capacitance vessels in vivo. Circulation, 1995,92 (3):357-363.
[1]. Naghavi M, Libby P, Falk E, et al. From vulnerable plaque to vulnerable patient:a call for new definitions and risk assessment strategies:Part I. Circulation,2003,108 (14):1664-1672.
[2]. Paramo JA. The hemostatic system as a modulator of atherosclerosis. N Engl J Med, 2011,365 (3):278-279.
[3]. Virmani R, Burke AP, Farb A, et al. Pathology of the Vulnerable Plaque. J Am Coll Cardiol,2006,47 (8):C13-18.
[4]. Schaar JA, Muller JE, Falk E,et al. Terminology for high-risk and vulnerable coronary artery plaques:Report of a meeting on the vulnerable plaque. June 17-18,2003, Santorini, Greece. Eur Heart J,2004,25:1077-1082.
[5]. Schwartz SM, Galis ZS, Rosenfeld ME, et al. Plaque rupture in humans and mice. Arterioscler Thromb Vase Biol,2007,27 (4):705-713.
[6]. Skalen K, Gustafsson M, Rydberg EK,et al. Subendothelial retention of atherogenic lipoproteins in early atherosclerosis. Nature.2002,417 (6890):750-754.
[7]. Leitinger N. Oxidized phospholipids as modulators of inflammation in atherosclerosis. Curr Opin Lipidol.2003,14 (5):421-430.
[8]. Cybulsky MI, Gimbrone MA Jr. Endothelial expression of mononuclear leukocyte adhesion molecule during atherogenesis. Science,1991,251 (4995):788-791.
[9]. Janeway CA, Jr, Medzhitov R. Innate immune recognition. Annu Rev Immunol,2002, 20:197-216.
[10]. Moreno PR, Purushothaman KR, Sirol M, et al. Neovascularization in human atherosclerosis. Circulation,2006,113 (18):2245-2252.
[11]. Patel VA, Zhang QJ, Siddle K, et al. Defect in insulin-like growth factor-1 survival mechanism in atherosclerotic plaque-derived vascular smooth muscle cells is mediated by reduced surface binding and signaling. Circ Res,2001,88 (9):895-902.
[12]. Moreau M, Brocheriou I, Petit L, et al. Interleukin-8 mediates downregulation of tissue inhibitor of metalloproteinase-1 expression in cholesterol-loaded human macrophages:relevance to stability of atherosclerotic plaque. Circulation,1999,99 (3):420-426.
[13]. Ambrose JA. In search of the "vulnerable plaque":can it be localized and will focal regional therapy ever be an option for cardiac prevention? J Am Coll Cardiol,2008, 51 (16):1539-1542.
[14]. Corti R, Fuster V, Badimon JJ. Pathogenetic concepts of acute coronary syndromes. J Am Coll Cardiol,2003,41 (4):7S-14S.
[15]. Ridker PM, Buring JE, Rifai N. Soluble P-selectin and the risk of future cardiovascular events. Circulation,2001,103 (4):491-495.
[16]. Pradhan AD, Rifai N, Ridker PM. Soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and the development of symptomatic peripheral arterial disease in men. Circulation,2002,106 (7):820-825.
[17]. Ridker PM, Rifai N, Stampfer MJ, et al. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation,2000, 101 (15):1767-1772.
[18]. Ridker PM, Rifai N, Pfeffer M, et al. Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction. Circulation, 2000,101 (18):2149-2153.
[19]. Blankenberg S, Tiret L, Bickel C, et al. Interleukin-18 is a strong predictor of cardiovascular death in stable and unstable angina. Circulation,2002,106 (1):24-30.
[20]. Kolodgie FD, Virmani R, Burke AP, et al. Pathologic assessment of the vulnerable human coronary plaque. Heart,2004,90 (12):1385-1391.
[21]. Virmani R, Kolodgie FD, Burke AP, et al. Lessons from sudden coronary death:a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol,2000,20 (5):1262-1275.
[22]. Moulton KS, Vakili K, Zurakowski D, et al. Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis. Proc Natl Acad Sci USA,2003,100 (8):4736-4741..
[23]. Moulton KS, Heller E, Konerding MA, et al. Angiogenesis inhibitor endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. Circulation,1999,99:1726-1732.
[24]. Pels K, Labinaz M, O'Brien ER. Arterial wall neovascularization - potential role in atherosclerosis and restenosis. Jpn Circ J,1997,61 (11):893-904.
[25]. Bank AJ, Versluis A, Dodge SM, et al. Atherosclerotic plaque rupture:a fatigue process? Med Hypotheses,2000,55 (6):480-484.
[26]. Moreno PR, Purushothaman KR, Fuster V, et al. Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta:implications for plaque vulnerability, Circulation,2004,110 (14):2032-2038.
[27]. Kolodgie, F.D., et al., Intraplaque hemorrhage and progression of coronary atheroma. N Engl J Med,2003.349 (24):2316-2325.
[28]. Langheinrich AC, Kampschulte M, Buch T, et al. Vasa vasorum and atherosclerosis-Quid novi? Thromb Haemost,2007,97 (6):873-879.
[29]. Rosenzweig A. Endothelial progenitor cells.N Engl J Med,2003,348 (7):581-582.
[30]. Simons M. Angiogenesis:where do we stand now? Circulation,2005,111 (12):1556-1566.
[31]. Williams JK, Armstrong ML, Heistad DD. Vasa vasorum in atherosclerotic coronary arteries:responses to vasoactive stimuli and regression of atherosclerosis. Circ Res, 1988,62 (3):515-523.
[32]. Kolodgie FD, Gold HK, Burke AP, et al. Intraplaque hemorrhage and progression of coronary atheroma. N Engl J Med,2003,349 (24):2316-2325.
[33]. Brownlee. Biochemistry and molecular cell biology of diabetic complications. Nature, 2001,414 (6865):813-820.
[34]. Graversen JH, Madsen M, Moestrup SK. CD 163:a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma.Int J Biochem Cell Biol,2002,34 (4):309-314.
[35]. Moreno PR, Purushothaman KR, Purushothaman M, et al. Haptoglobin genotype is a major determinant of the amount of iron in the human atherosclerotic plaque. J Am Coll Cardiol.2008,52 (13):1049-1051.
[36]. Levy AP, Roguin A, Hochberg I, et al. Haptoglobin phenotype and vascular complications in patients with diabetes. N Engl J MED,2000,343 (13):969-970.
[37]. Touboul PJ, Hernandez-Hernandez R, Kucukoglu S, et al. Carotid artery intima media thickness, plaque and Framingham cardiovascular score in Asia, Africa/Middle East and Latin America:the PARC-AALA study. Int J Cardiovasc Imaging,2007,23 (5): 557-567.
[38]. Lorenz MW, Markus HS, Bots ML, et al. Prediction of clinical cardiovascular events with carotid intima-media thickness:a systematic review and meta-analysis. Circulation,2007,115 (4):459-467.
[39]. Prati P, Tosetto A, Vanuzzo D, et al. Carotid intima media thickness and plaques can predict the occurrence of ischemic cerebrovascular events. Stroke,2008,39 (9):2470-2476.
[40]. Coll B, Feinstein SB. Carotid intima-media thickness measurements:techniques and clinical relevance. Curr Atheroscler Rep,2008,10 (5):444-450.
[41]. Jager KA, Staub D. Did you measure the intima-media thickness? Ultraschall Med, 200930 (5):434-437.
. [42]. Chambless LE, Folsom AR, Clegg LX, et al. Carotid wall thickness is predictive of incident clinical stroke:the Atherosclerosis Risk in Communities (ARIC) study. Am J Epidemiol,2000,151 (5):478-487.
[43]. Gronholdt ML, Nordestgaard BG, Bentzon J, et al. Macrophages are associated with lipid-rich carotid artery plaques, echolucency on B-mode imaging, and elevated plasma lipid levels. J Vasc Surg,2002,35 (1):137-145.
[44]. Coli S, Magnoni M, Sangiorgi G, et al. Contrast-enhanced ultrasound imaging in intraplaque neovascularization in carotid arteries:correlation with histology and plaque echogenicity. J Am Coll Cardiol,2008,52 (3):223-230.
[45]. Staub D, Partovi S, Schinkel AF, et al. Correlation of carotid artery atherosclerotic lesion echogenicity and severity at standard US with intraplaque neovascularization detected at contrast-enhanced US. Radiology.2011,258 (2):618-626.
[46]. Xiong L, Deng YB, Zhu Y, et al. Correlation of carotid plaque neovascularization detected by using contrast-enhanced US with clinical symptoms. Radiology,2009, 251 (2):583-589.
[47].周巧兰,李治安,勇强,等.超声二维应变成像技术评价颈动脉粥样硬化斑块力学状态的初步研究.心肺血管病杂志,2010,29(4)：287-290.
[48].朱英,邓又斌,毕小军,等.超声二维应变技术评价动脉粥样硬化颈动脉壁弹性.中国医学影像技术,2008,24(9)：1379-1381.
[49]. Kerwin WS, O'Brien KD, Ferguson MS, et al. Inflammation in carotid atherosclerotic plaque:a dynamic contrast-enhanced MR imaging study. Radiology,2006,241 (2): 459-468.
[50]. Baker KP, Katsafados MG, Chatzopoulos DN, et al. Inflammatory markers and plaque morphology:an optical coherence tomography study. Int J Cardiol,2012,154 (3):287-292.
[51]. Tabas I. Macrophage death and defective inflammation resolution in atherosclerosis. Nat Rev Immunol,2010,10 (1):36-46.
[52]. Winter PM, Morawski AM, Caruthers SD, et al. Molecular imaging of angiogenesis in early-stage atherosclerosis with alpha (v) beta3-integrin-targeted nanoparticles. Circulation,2003,108 (18):2270-2274.
[53]. Tabas I. Pulling down the plug on atherosclerosis:finding the culprit in your heart. Nat MED,2011,17 (7):791-793.
[54]. Kolodgie F D, Narula J, Haider N, et al. Apoptosis in atherosclerosis. Does it contribute to plaque instability? Cardiol Clin,2001,19 (1):127-139.
[55]. Gao T, Zhang Z, Yu W,et al. Atherosclerotic carotid vulnerable plaque and subsequent stroke:a high-resolution MRI study. Cerebrovasc Dis,2009,27 (4): 345-352.
[56]. Derksen WJ, Peeters W, van Lammeren GW, et al. Different stages of intraplaque hemorrhage are associated with different plaque phenotypes:a large histopathological study in 794 carotid and 276 femoral endarterectomy specimens. Atherosclerosis, 2011,218 (2):369-377.
[57]. Ouimet T, Lancelot E, Hyafil F, et al. Molecular and cellular targets of the MRI contrast agent p947 for atherosclerosis imaging. Mol Pharm,2012,9 (4):850-861.
[58]. Lancelot E, Amirbekian V, Brigger I, et al. Evaluation of matrix metalloproteinases in atherosclerosis using a novel noninvasive imaging approach. Arterioscler Thromb Vase Biol,2008,28 (3):425-432.
[59]. Bazeli R, Coutard M, Duport BD,et al. In vivo evaluation of a new magnetic resonance imaging contrast agent (P947) to target matrix metalloproteinases in expanding experimental abdominal aortic aneurysms. Invest Radiol,2010,45 (10): 662-668.
[60]. Johnson JL, George SJ, Newby AC, et al. Divergent effects of matrix metalloproteinases 3,7,9, and 12 on atherosclerotic plaque stability in mouse brachiocephalic arteries. Proc Natl Acad Sci USA,2005,102 (43):15575-15580.
[61]. Loftus IM, Naylor AR, Bell PR, et al. Matrix metalloproteinases and atherosclerotic plaque instability. Br J Surg,2002,89 (6):680-694.
[62]. Vengrenyuk Y, Cardoso L, Weinbaum S. Micro-CT based analysis of a new paradigm for vulnerable plaque rupture:cellular microcalcifications in fibrous caps. Mol Cell Biomech,2008,5(1):37-47.
[63]. Vengrenyuk Y, Carlier S, Xanthos S, et al. A hypothesis for vulnerable plaque rupture due to stress-induced debonding around cellular microcalcifications in thin fibrous caps. Proc Natl Acad Sci USA,2006,103 (40):14678-14683.
[64]. Slager CJ, Wentzel JJ, Gijsen FJ, et al. The role of shear stress in the generation of rupture-prone vulnerable plaques. Nat Clin Pract Cardiovasc Med,2005,2 (8): 401-407.
[65]. Bennett MR. Life and death in the atherosclerotic plaque. Curr Opin Lipidol,2010,21 (5):422-426.
[66]. Schoenenberger AW, Urbanek N, Bergner M, et al. Associations of reactive hyperemia index and intravascular ultrasound-assessed coronary plaque morphology in patients with coronary artery disease. Am J Cardiol,2012,109 (12):1711-1716.
[67]. Tabas I. Macrophage apoptosis in atherosclerosis:consequences on plaque progression and the role of endoplasmic reticulum stress. Antioxid Redox Signal, 2009,11 (9):2333-2339.
[68]. Van Vre EA, Ait-Oufella H, Tedgui A, et al. Apoptotic cell death and efferocytosis in atherosclerosis. Arterioscler Thromb Vasc Biol,2012,32(4):887-893.
[69]. Schrijvers DM, De Meyer GR, Kockx MM, et al. Phagocytosis of apoptotic cells by macrophages is impaired in atherosclerosis. Arterioscler Thromb Vasc Biol,2005,25 (6):1256-1261.
[70]. Thorp E, Tabas I. Mechanisms and consequences of efferocytosis in advanced atherosclerosis. J Leukoc Biol,2009,86 (5):1089-1095.
[71]. Snow M, Ben-Sassi A, Winter RK, et al. Can carotid ultrasound predict plaque histopathology? Cardiovasc Surg (Torino),2007,48 (3):299-303.
[72]. Barry MJ, Richardson PD, Woolf N, et a 1. Accuracy of B-mode ultrasonography in detecting carotid plaque hemorrhage and ulceration. J Ann Va sc Surg,1990,4 (5):466-470.
[73]. Feinstein SB. Contrast ultrasound imaging of the carotid artery vasa vasorum and atherosclerotic plaque neovascularization. J Am Coll Cardiol,2006,48 (2):236-243.
[74]. Shalhoub J, Owen DR, Gauthier T, et al. The use of contrast enhanced ultrasound in carotid arterial disease. Eur J Vasc Endovasc Surg,2010,39:381-387.
[75]. Staub D, Patel MB, Tibrewala A, et al. Vasa vasorum and plaque neovascularization on contrast-enhanced carotid ultrasound imaging correlates with cardiovascular disease and past cardiovascular events. Stroke,2010,41 (1):41-47.
[76]. Staub D, Partovi S, Schinkel AF, et al. Correlation of carotid artery atherosclerotic lesion echogenicity and severity at standard US with intraplaque neovascularization detected at contrast-enhanced US. Radiology,2011,258 (2):618-626.
[77]. Feinstein SB, Coll B, Staub D, et al. Contrast enhanced ultrasound imaging. J Nucl Cardio12010,17 (1):106-115.
[78]. Vicenzini E, Giannoni MF, Puccinelli F, et al. Detection of carotid adventitial vasa vasorum and plaque vascularization with ultrasound cadence contrast pulse sequencing technique and echo-contrast agent. Stroke,2007,38 (10):2841-2843.
[79]. Clevert DA, Sommer WH, Helck A, et al. Improved carotid atherosclerotic plaques imaging with contrast-enhanced ultrasound (CEUS). Clin Hemorheol Microcirc,2011, 48(1):141-148.
[80]. Huang PT, Huang FG, Zou CP, et al. Contrast-enhanced sonographic characteristics of neovascularization in carotid atherosclerotic plaques. J Clin Ultrasound,2008,36 (6):346-351.
[81]. Schinkel AF, Krueger CG, Tellez A, et al. Contrast-enhanced ultrasound for imaging vasa vasorum:comparison with histopathology in a swine model of atherosclerosis. Eur J Echocardiogr.2010,11 (8):659-664.
[82]. Shah F, Balan P, Weinberg M, et al. Contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization:new surrogate marker of atherosclerosis? Vasc Med,2007,12 (4):291-297.
[83]. Giannoni MF, Vicenzini E, Citone M, et al. Contrast carotid ultrasound for the detection of unstable plaques with neoangiogenesis:a pilot study. Eur J Vasc Endovasc Surg,2009,37 (6):722-727.
[84].张莹,黄品同,杨琰,等.超声造影对脑梗死患者颈动脉粥样斑块的评价.中国超声医学杂志.2009,25(1)：16-19.
[85]. Clevert DA, Sommer WH, Helck A, et al. Improved carotid atherosclerotic plaques imaging with contrast-enhanced ultrasound (CEUS). Clin Hemorheol Microcirc,2011, 48 (1):141-148.
[86].何文.颈动脉斑块内新生血管的研究现状.中国卒中杂志,2009,4(7)：585-589.
[87]. Fleiner M, Kummer M, Mirlacher M, et al. Arterial neovascularization and inflammation in vulnerable patients:early and late signs of symptomatic atherosclerosis. Circulation,2004,110 (18):2843-2850.
[88].魏立亚,何文,张红霞,等.缺血性卒中患者颈动脉硬化斑块内新生血管的超声造影研究.中国卒中杂志,2009,4(11)：898-902.
[89].熊莉,邓又斌,毕小军,等.超声造影评价颈动脉粥样斑块稳定性.中华超声影像学杂志,2008,17(3)：214-216.
[90]. Faggioli GL, Pini R, Mauro R, et al. Identification of carotid'vulnerable plaque' by contrast-enhanced ultrasonography:correlation with plaque histology, symptoms and cerebral computed tomography. Eur J Vasc Endovasc Surg,2011,41 (2):238-248.
[91]. Tian J, Hu S, Sun Y, et al. Vasa vasorum and plaque progression, and responses to atorvastatin in rabbit model of atherosclerosis:contrast-enhanced ultrasound imaging and intravascular ultrasound study. Heart,2013,99 (1):48-54.
[92]. Jain RK, Finn AV, Kolodgie FD, et al. Antiangiogenic therapy for normalization of atherosclerotic plaque vasculature:a potential strategy for plaque stabilization. Nat Clin Pract Cardiovasc Med,2007,4 (9):491-450.
[93]. Tanaka H, Zaima N, Sasaki T, et al. Adventitial vasa vasorum arteriosclerosis in abdominal aortic aneurysm. PLoS One,2013,8 (2):p. e57398.
[94]. Macura KJ, Corl FM, Fishman EK, et al. Pathogenesis in acute aortic syndromes: aortic dissection, intramural hematoma, and penetrating atherosclerotic aortic ulcer. AJR Am J Roentgenol,2003,181 (2):309-316.
[95]. Coady MA, Rizzo JA, Elefteriades JA. Rizzo, et al. Pathologic variants of thoracic aortic dissections. Penetrating atherosclerotic ulcers and intramural hematomas. Cardiol Clin,1999,17 (4):637-657.
[96]. Scotlan d RS, Vallance PJT, Ahlu walia A. Endogenous factors involved in regulation of tone of arterial Vasa vasorum:implications for conduit vessel physiology. Cardiovasc Res,2000,46 (3):403-411.
[97]. Sacks AH. The vasa vasorum as a link between hypertension and arteriosclerosis. Angiology,1975,26:385-390.
[98]. Nakamura K, Onitsuka T, Yano M, et al. Clinical analysis of acute type A intramural hematoma:comparison between two different pathophysiological types. Ann Thorac Surg,2006.81 (5):1587-1592.
[99]. Baikoussis NG, Apostolakis EE. Penetrating atherosclerotic ulcer of the thoracic aorta: diagnosis and treatment. Hellenic J Cardiol,2010,51 (2):153-157.
[100]. Kwon HM, Sangiorgi G, Ritman EL, et al. Adventitial vasa vasorum in balloon-injured coronary arteries:visualization and quantitation by a microscopic three-dimensional computed tomography technique. J Am Coll Cardiol,1998.32 (7): 2072-2079.
[101]. Feinstein SB. The powerful microbubble:from bench to bedside, from intravascular indicator to therapeutic delivery system, and beyond. Am J Physiol Heart Circ Physiol, 2004,287 (2):H450-457.
[102]. Magnoni M, Coli S, Marrocco-Trischitta MM, et al. Contrast-enhanced ultrasound imaging of periadventitial vasa vasorum in human carotid arteries. Eur J Echocardiogr. 2009,10 (2):260-264.
[103], Staub D, Schinkel AF, Coll B, et al. Contrast-enhanced ultrasound imaging of the vasa vasorum:from early atherosclerosis to the identification of unstable plaques. JACC Cardiovasc Imaging,2010,3 (7):761-771.
[104]. Lee SC, Carr CL, Davidson BP, et al. Temporal characterization of the functional density of the vasa vasorum by contrast-enhanced ultrasonography maximum intensity projection imaging. JACC Cardiovasc Imaging,2010,3 (12):1265-1272.
[105]. Moguillansky D, Leng X, Carson A, et al. Quantification of plaque neovascularization using contrast ultrasound:a histologic validation. Eur Heart J,2011,32 (5):646-653.
[106]. Goertz DE, Frijlink ME, Krams R. et al. Vasa vasorum and molecular imaging of atherosclerotic plaques using nonlinear contrast intravascular ultrasound. Neth Heart J, 2007,15 (2):77-80.
[107]. Goertz DE, Frijlink ME, de Jong N, et al. Nonlinear intravascular ultrasound contrast imaging. Ultrasound Med Biol,2006,32 (4):491-502.
[108]. Carlier S, Kakadiaris IA, Dib N, et al. Vasa vasorum imaging:a new window to the clinical detection of vulnerable atherosclerotic plaques. Curr Atheroscler Rep,2005,7 (2):164-169.
[109]. Vavuranakis M, Papaioannou TG, Kakadiaris IA, et al. Detection of perivascular blood flow in vivo by contrast-enhanced intracoronary ultrasonography and image analysis:an animal study. Clin Exp Pharmacol Physiol,2007,34 (12):1319-1323.
[110]. Vavuranakis M, Kakadiaris IA, O'Malley SM, et al. A new method for assessment of plaque vulnerability based on vasa vasorum imaging by using contrast-enhanced intravascular ultrasound and differential image analysis. Int J Cardiol,2008,130 (1): 23-29.
[111]. O'Malley SM, Vavuranakis M, Naghavi M, et al. Intravascular ultrasound-based imaging of vasa vasorum for the detection of vulnerable atherosclerotic plaque. Med Image Comput Comput Assist Interv,2005,8 (Pt 1):343-351.
[112]. Vander Steen AF, Baldewsing RA, Levent Degertekin F, et al. IVUS beyond the horizon. EuroIntervention,2006,2(1):132-142.
[113]. Filipovic N, Teng Z, Radovic M, et al. Computer simulation of three-dimensional plaque formation and progression in the carotid artery. Med Biol Eng Comput,2013 Jan 25. [Epub ahead of print].
[114]. Busch M, Zernecke A. microRNAs in the regulation of dendritic cell functions in inflammation and atherosclerosis. J Mol Med (Berl),2012,90 (8):877-885.
[115]. Weber C, Noels H. Atherosclerosis:current pathogenesis and therapeutic options. Nat Med,2011,17 (11):1410-1422.
[116]. Blann AD, Nadar SK, Lip GY. The adhesion molecule P-selectin and cardiovascular disease. Eur Heart J,2003,24 (24):2166-2179.
[117].Weller GE, Lu E, Csikari MM, et al. Ultrasound imaging of acute cardiac transplant rejection with microbubbles targeted tointercellular adhesion molecule-1. Circulation, 2003,108 (2):218-224.
[118]. Bachmann C, Klibanov AL, Olson TS, et al. Targeting mucosal addressin cellular adhesion molecule (MAdCAM)-1 to noninvasively image experimental Crohn's disease. Gastroenterology,2006,130 (1):8-16.
[119]. Liu H, Wang X, Tan KB, et al. Molecular imaging of vulnerable plaques in rabbits using contrast-enhanced ultrasound targeting to vascular endothelial growth factor receptor-2. J Clin Ultrasound,2011,39 (2):83-90.
[120]. Lu Y, Wei J, Shao Q, et al. Assessment of atherosclerotic plaques in the rabbit abdominal aorta with interleukin-8 monoclonal antibody-targeted ultrasound microbubbles. Mol Biol Rep,2013,40 (4):3083-3092.
[121]. Hamilton AJ, Huang SL, Warnick D, et al. Intravascular ultrasound molecular imaging of atheroma components in vivo. J Am Coll Cardiol,2004,43 (3):453-460.
[122]. Kaufmann BA, Sanders JM, Davis C, et al. Molecular imaging of inflammation in atherosclerosis with targeted ultrasound detection of vascular cell adhesion molecule-1. Circulation,2007,116 (3):276-284.
[123]. Kaufinann BA, Carr CL, Belcik JT, et al. Molecular imaging of the initial inflammatory response in atherosclerosis:implications for early detection of disease. Arterioscler Thromb Vasc Biol,2010,30 (1):54-59.
[124]. Caplan ES, Khangura J, Bullens S, et al. Molecular imaging of the initial inflammatory response in atherosclerosis:implications for early detection of disease. Arterioscler Thromb Vasc Biol,2010,30 (1):54-59.
[125]. Behm CZ, Kaufmann BA, Carr C, et al. Molecular imaging of endothelial vascular cell adhesion molecule-1 expression and inflammatory cell recruitment during vasculogenesis and ischemia-mediated arteriogenesis. Circulation,2008,117 (22): 2902-2911.
[126]. Wu J, Leong-Poi H, Bin J, et al. Efficacy of contrast-enhanced US and magnetic microbubbles targeted to vascular cell adhesion molecule-1 for molecular imaging of atherosclerosis. Radiology,2011,260 (2):463-471..
[127]. Klibanov AL, Rychak JJ, Yang WC, et al. Targeted ultrasound contrast agent for molecular imaging of inflammation in high-shear flow. Contrast Media Mol Imaging, 2006,1 (6):259-266.
[128]. Ferrante EA, Pickard JE, Rychak J, et al. Dual targeting improves microbubble contrast agent adhesion to VCAM-1 and P-selectin under flow. J Control Release, 2009,140 (2):100-107.
[129]. Warram JM, Sorace AG, Saini R, et al. A triple-targeted ultrasound contrast agent provides improved localization to tumor vasculature. J Ultrasound Med,2011,30 (7): 921-931.
2 Virmani R, Burke AP, Farb A, et al. Pathology of the Vulnerable Plaque. J Am Coll Cardiol,2006,47(8):13-18.
3 Macura KJ, Corl FM, Fishman EK, et al. Pathogenesis in acute aortic syndromes:aortic dissection, intramural hematoma, and penetrating atherosclerotic aortic ulcer. AJR Am J Roentgenol,2003,181 (2):309-316.
4 Wolinsky H, Glagov S. Nature of species differences in the medial distribution of aortic vasa vasorum in mammals. Circ Res,1967,20 (4):409-421.
5 Heistad DD, Armstrong ML, Amundsen S. Blood flow through vasa vasorum in arteries and veins:effects of luminal PO2. Am J Physiol,1986,250 (3 Pt 2):H434-442.
6 Herbst WM, Eberle KP, Ozen Y, et al. The innervation of the great saphenous vein:an immunohistochemical study with special regard to regulatory peptides. Vasa,1992,21 (3):253-257.
7 Ritm an LE, Lerman A. Role of vasa vasorum in arterial disease:a re-emerging factor. Curr Cardiol Rev,2007,3 (1):43- 55.
8 Scotlan d RS, Vallance PJT, Ahlu walia A. Endogenous factors involved in regulation of tone of arterial vasa vasorum:implications for conduit vessel physiology. Cardiovasc Res,2000,46(3):403-411.
9 Ohhira A, Ohhashi T. Effects of aortic pressure and vasoactive agents on the vascular resistance of the vasa vasorum in canine vessels results in vascular lesions and certain vascula r isolated thoracic aorta. J Physiol,1992,453:233-245.
10 Scotlan d RS, Vallance P, Ahluw alia A. On the regulation of tone in vasa vasorum. Cardiov asc Res,1999,41 (1):237-245.
11 Scotland R, Vallance P, Ahluwalia A. Endothelin alters the reactivity of vasa vasorum: mechanisms and implications for conduit vessel physiology and pathophysiology. Br J Pharmacol,1999,128 (6):1229-1234.
12 Carlier S, Kakadiaris IA, Dib N, et al. Vasa vasorum imaging:a new window to the clinical detection of vulnerable atherosclerotic plaques. Curr Atheroscler Rep,2005,7 (2):164-169.
13 Juan-Babot JO, Martinez-Gonzalez J, Berrozpe M, et al. Neovascularization in human coronary arteries with lesions of different severity, Rev Esp Cardiol,2003,56 (10):978-986.
14 Moreno PR, Purushothaman KR, Fuster V, et al. Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta:implications for plaque vulnerability. Circulation,2004,110 (14):2032-2038.
15 Heistad DD, Marcus ML, Larsen GE, et al. Role of vasa vasorum in nourishment of the aortic wall. Am J Physiol.1981,240 (5):H781-787.
16 Virmani R, Kolodgie FD, Burke AP, et al. Atherosclerotic plaque progression and vulnerability to rupture:angiogenesis as a source of intraplaque hemorrhage. Arterioscler Thromb Vasc Biol,2005,25 (10):2054-2061.
17 Virmani R, Kolodgie FD, Burke AP, et al. Lessons from sudden coronary death:a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol,2000,20 (5):1262-1275.
18 Fleiner M, Kummer M, Mirlacher M, et al. Arterial neovascularization and inflammation in vulnerable patients:early and late signs of symptomatic atherosclerosis. Circulation,2004,110 (18):2843-2850.
19 Feinstein SB. The powerful microbubble:from bench to bedside, from intravascular indicator to therapeutic delivery system, and beyond. Am J Physiol Heart Circ Physiol, 2004,287 (2):H450-457.
1 Hoogi A, Adam D, Hoffman A, et al. Carotid plaque vulnerability:quantification of neovascularization on contrast-enhanced ultrasound with histopathologic correlation. AJRAm J Roentgenol,2011,196,431-436.
2 Carlier S, Kakadiaris IA, Dib N, et al. Vasa vasorum imaging:a new window to the clinical detection of vulnerable atherosclerotic plaques. Curr Atheroscler Rep,2005, 7:164-169.
3 Moreno PR, Purushothaman KR, Sirol M, et al. Neovascularization in human atherosclerosis. Circulation,2006,113:2245-2252.
4 Sluimer JC, Daemen MJ. Novel concepts in atherogenesis:angiogenesis and hypoxia in atherosclerosis. J Pathol,2009,218:7-29.
5 Staub D, Schinkel AF, Coll B, et al. Contrast-enhanced ultrasound imaging of the vasa vasorum:from early atherosclerosis to the identification of unstable plaques. JACC Cardiovasc Imaging,2010,3:761-771.
6 Dunmore BJ, McCarthy MJ, Naylor AR, et al. Carotid plaque instability and ischemic symptoms are linked to immaturity of micro vessels within plaques. J Vase Surg,2007, 45:155-159.
7熊莉,邓又斌,毕小军,等.超声造影评价颈动脉粥样斑块稳定性.中华超声影像学杂志,2008,17：214-216.
8 Xiong L, Deng YB, Zhu Y, et al. Correlation of carotid plaque neovascularization detected by using contrast-enhanced US with clinical symptoms. Radiology,2009, 251(2):583-589.
9 Shalhoub J, Owen DR, Gauthier T, et al. The use of contrast enhanced ultrasound in carotid arterial disease. Eur J Vase Endovasc Surg,2010,39:381-387.
10 Staub D, Patel MB, Tibrewala A, et al. Vasa vasorum and plaque neovascularization on contrast-enhanced carotid ultrasound imaging correlates with cardiovascular disease and past cardiovascular events. Stroke,2010,41:41-47.
11 Staub D, Partovi S, Schinkel AF, et al. Correlation of carotid artery atherosclerotic lesion echogenicity and severity at standard US with intraplaque neovascularization detected at contrast-enhanced US. Radiology,2011,258:618-626.
12 Feinstein SB, Coll B, Staub D, et al. Contrast enhanced ultrasound imaging. J Nucl Cardiol 2010,17:106-115.
13 Vicenzini E, Giannoni MF, Puccinelli F, et al. Detection of carotid adventitial vasa vasorum and plaque vascularization with ultrasound cadence contrast pulse sequencing technique and echo-contrast agent. Stroke,2007,38:2841-2843.
14 Feinstein SB. The powerful microbubble:from bench to bedside, from intravascular indicator to therapeutic delivery system, and beyond. Am J Physiol Heart Circ Physiol, 2004,287:H451-H457.
15朱英,邓又斌,刘娅妮,等.超声造影成像技术评价颈动脉斑块内新生血管与斑块声学特性的关系.中华医学超声杂志(电子版),2009,5：882-886.
16 Shah F, Balan P, Weinberg M,et al. Contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization a new surrogate marker of atherosclerosis. Vasc Med,2007,12:291-297.
1 Hoogi A, Adam D, Hoffman A, et al. Carotid plaque vulnerability:quantification of neovascularization on contrast-enhanced ultrasound with histopathologic correlation. AJR Am J Roentgenol,2011,196(2):431-436.
2 Carlier S, Kakadiaris IA, Dib N, et al. Vasa vasorum imaging:a new window to the clinical detection of vulnerable atherosclerotic plaques. Curr Atheroscler Rep,2005,7 (2):164-169.
3 Heistad DD, Marcus ML, Larsen GE, et al. Role of vasa vasorum in nourishment of the aortic wall. Am J Physiol,1981,240 (5):H781-787.
4 Moreno PR, Purushothaman KR, Sirol M, et al. Neovascularization in human atherosclerosis. Circulation,2006,113 (18):2245-2252.
5 Virmani R, Kolodgie FD, Burke AP, et al. Atherosclerotic plaque progression and vulnerability to rupture:angiogenesis as a source of intraplaque hemorrhage. Arterioscler Thromb Vasc Biol,2005,25(10):2054-2061.
6 Fleiner M, Kummer M, Mirlacher M, et al. Arterial neovascularization and inflammation in vulnerable patients:early and late signs of symptomatic atherosclerosis. Circulation,2004,110 (18):2843-2850.
7 Feinstein SB. Contrast ultrasound imaging of the carotid artery vasa vasorum and atherosclerotic plaque neovascularization. J Am Coll Cardiol,2006,48 (2):236-243.
8 Xiong L, Deng YB, Zhu Y, et al. Correlation of carotid plaque neovascularization detected by using contrast-enhanced US with clinical symptoms. Radiology,2009, 251 (2):583-589.
9 Staub D, Partovi S, Schinkel AF, et al. Correlation of carotid artery atherosclerotic lesion echogenicity and severity at standard US with intraplaque neovascularization detected at contrast-enhanced US. Radiology,2011,258 (2):618-626.
10朱英,邓又斌,刘娅妮,等.超声造影成像技术评价颈动脉斑块内新生血管与斑块声学特性的关系.中华医学超声杂志(电子版),2009；6(5)：882-886.
11 Vicenzini E, Giannoni MF, Puccinelli F, et al. Detection of carotid adventitial vasa vasorum and plaque vascularization with ultrasound cadence contrast pulse sequencing technique and echo-contrast agent. Stroke,2007,38 (10):2841-2843.
12 Papaioannou TG, Vavuranakis M, Androulakis A, et al. In-vivo imaging of carotid plaque neoangiogenesis with contrast-enhanced harmonic ultrasound. Int J Cardiol, 2009,134 (3):110-112.
13 Magnoni M, Coli S, Marrocco-Trischitta MM, et al. Contrast-enhanced ultrasound imaging of periadventitial vasa vasorum in human carotid arteries. Eur J Echocardiogr, 2009,10 (2):260-264.
14 Wilens SL, Plair CM. Blood cholesterol, nutrition, therosclerosis. anecropsy study. Arch Intern Med,1965,116:373-380.
15 Ritman LE, Lerman A. Role of vasa vasorum in arterial disease:a re-emerging factor. Curr Cardiol Rev,2007,3 (1):43-55.
16 Scotland RS, Vallance PJ, Ahluwalia A. Endogenou s factors involved in regulation of tone of arterial vasa vasorum:implications for conduit vessel physiology. Cardiovasc Res,2000,46 (3):403-411.
17 Ritman EL, Lerman A. The dynamic vasa vasorum. Cardiovasc Res,2007,75 (4):649-658.
18 Ohhira A, Ohhashi T. Effects of aortic pressure and vasoactive agents on the vascular resistance of the vasa vasorum in canine vessels results in vascular lesions and certain vascular isolated thoracic aorta. J Physiol,1992,453:233-245.
19 Sacks AH. The vasa vasorum as a link between hypertension and arteriosclerosis. Angiology,1975,26:385-390.
20熊莉,邓又斌,毕小军,等.超声造影评价颈动脉粥样斑块稳定性.中华超声影像学杂志,2008,17(3)：214-216.
21杨宝峰,苏定冯主编.药理学.第6版,北京：人民卫生出版社,2004：89-93.
22 Gossl M, Rosol M, Malyar NM, et al. Functional anatomy and hemodynamic characteristics of vasa vasorum in the walls of porcine coronary arteries. Anat Rec A Discov Mol Cell Evol Biol,2003,272 (2):526-537.
23 Den Hartog JP. Strength of materials. New York:Dover Publications, Inc,1949, p323.
24 Guan Z, Inscho EW. Role of adenosine 5'-triphosphate in regulating renal microvascular function and in hypertension. Hypertension,2011,58 (3):333-340.
1 Hoogi A, Adam D, Hoffman A, et al. Carotid plaque vulnerability:quantification of neovascularization on contrast-enhanced ultrasound with histopathologic correlation. AJR Am J Roentgenol,2011,196 (2):431-436.
2 Casscells W, Naghavi M, Willerson JT. Vulnerable atherosclerotic plaque:a multifocal disease. Circulation,2003,107 (16):2072-2075.
3 Virmani R, Burke AP, Farb A,et al. Pathology of the Vulnerable Plaque. J Am Coll Cardiol,2006,47 (8):13-18.
4 Fleiner M, Kummer M, Mirlacher M, et al. Arterial neovascularization and inflammation in vulnerable patients:early and late signs of symptomatic atherosclerosis. Circulation,2004,110 (18):2843-2850.
5 Dunmore BJ, McCarthy MJ, Naylor AR, et al. Carotid plaque instability and ischemic symptoms are linked to immaturity of microvessels within plaques. J Vase Surg,2007, 45 (1):155-159.
6 Feinstein SB. Contrast ultrasound imaging of the carotid artery vasa vasorum and atherosclerotic plaque neovascularization. J Am Coll Cardiol,2006,48 (2):236-243.
7 Carlier S, Kakadiaris IA, Dib N, et al. Vasa vasorum imaging:a new window to the clinical detection of vulnerable atherosclerotic plaques. Curr Atheroscler Rep,2005,7 (2):164-169.
8 Moreno PR, Purushothaman KR, Sirol M, et al. Neovascularization in human atherosclerosis. Circulation,2006,113 (18):2245-2252.
9 Xiong L, Deng YB, Zhu Y, et al. Correlation of carotid plaque neovascularization detected by using contrast-enhanced US with clinical symptoms. Radiology,2009, 251 (2):583-589.
10 Staub D, Partovi S, Schinkel AF, et al. Correlation of carotid artery atherosclerotic lesion echogenicity and severity at standard US with intraplaque neovascularization detected at contrast-enhanced US. Radiology,2011,258 (2):618-626.
11朱英,邓又斌,刘娅妮,等.超声造影成像技术评价颈动脉斑块内新生血管与斑 块声学特性的关系.中华医学超声杂志(电子版),2009;6(5)：882-886.
12 Vicenzini E, Giannoni MF, Puccinelli F, et al. Detection of carotid adventitial vasa vasorum and plaque vascularization with ultrasound cadence contrast pulse sequencing technique and echo-contrast agent. Stroke,2007,38 (10):2841-2843.
13 Papaioannou TQ Vavuranakis M, Androulakis A, et al. In-vivo imaging of carotid plaque neoangiogenesis with contrast-enhanced harmonic ultrasound. Int J Cardiol, 2009,134(3):110-112.
14 Magnoni M, Coli S, Marrocco-Trischitta MM, et al. Contrast-enhanced ultrasound imaging of periadventitial vasa vasorum in human carotid arteries. Eur J Echocardiogr, 2009,10 (2):260-264.
15 Moguillansky D, Leng X, Carson A, et al. Quantification of plaque neovascularization using contrast ultrasound:a histologic validation. Eur Heart J,2011,32 (5):646-653.
16 Wilens SL, Plair CM. Blood cholesterol, nutrition, therosclerosis. anecropsy study. Arch Intern Med,1965,116:373-380.
17 Scotlan d RS, Vallance PJT, Ahlu walia A. Endogenou s factors involved in regulat ion of tone of arterial vasa vasorum:imp lications for conduit vesse 1 physiology. Cardiovasc Res,2000,46 (3):403- 411.
18 Heistad D, Marcus M, Martin J. Effects of neural stimulion blood through vasa vasorum in dogs. Circ Res,1979,45 (5):615-620.
19 Scotlan d RS, Vallance P, Ahluw alia A. On the regulation of tone in vasa vasorum. Cardiov asc Res,1999,41 (1):237- 245.
20 Scotland R, Vallance P, Ahluwalia A. Endothelin alters the reactivity of vasa vasorum: mechanisms and implications for conduit vessel physiology and pathophysiology. Br J Pharmacol,1999,128 (6):1229-1234.
21熊莉,邓又斌,毕小军,等.超声造影评价颈动脉粥样斑块稳定性.中华超声影像学杂志.2008,17(3)：214-216.
22 Moncada S, Palmer RM, Higgs EA. Nitric Oxide:physiology, pathophysiology, and pharmacology. Pharmacol Rev,1991,43 (2):109-142.
23 Nadaud S, Bonnardeaux A, Lathrop M, et al. Gene structure polymorphism and mapping of the human endothelial nitric oxide synthase gene. Biochem Biophys Res Commun,1994,198 (3):1027-1033.
24 Lerman A, Edwards BS, Hallett JW, et al. Circulating and tissue endothelin immunoreactivity in advanced atherosclerosis. N Engl J Med,1991,325 (14): 997-1001.
25 Winkles JA, Alberts GF, Brogi E, et al. Endothelin-1 and endothelin receptor mRNA expression in normal and atherosclerotic human arteries. Biochem Biophys Res Commun,1993,191 (3):1081-1088.
26 Haynes WG, Strachan FE, Webb DJ. Endothelin ETA and ETB receptors cause vasoconstriction of human resistance and capacitance vessels in vivo. Circulation, 1995,92 (3):357-363.
[1]. Naghavi M, Libby P, Falk E, et al. From vulnerable plaque to vulnerable patient:a call for new definitions and risk assessment strategies:Part I. Circulation,2003,108 (14):1664-1672.
[2]. Paramo JA. The hemostatic system as a modulator of atherosclerosis. N Engl J Med, 2011,365 (3):278-279.
[3]. Virmani R, Burke AP, Farb A, et al. Pathology of the Vulnerable Plaque. J Am Coll Cardiol,2006,47 (8):C13-18.
[4]. Schaar JA, Muller JE, Falk E,et al. Terminology for high-risk and vulnerable coronary artery plaques:Report of a meeting on the vulnerable plaque. June 17-18,2003, Santorini, Greece. Eur Heart J,2004,25:1077-1082.
[5]. Schwartz SM, Galis ZS, Rosenfeld ME, et al. Plaque rupture in humans and mice. Arterioscler Thromb Vase Biol,2007,27 (4):705-713.
[6]. Skalen K, Gustafsson M, Rydberg EK,et al. Subendothelial retention of atherogenic lipoproteins in early atherosclerosis. Nature.2002,417 (6890):750-754.
[7]. Leitinger N. Oxidized phospholipids as modulators of inflammation in atherosclerosis. Curr Opin Lipidol.2003,14 (5):421-430.
[8]. Cybulsky MI, Gimbrone MA Jr. Endothelial expression of mononuclear leukocyte adhesion molecule during atherogenesis. Science,1991,251 (4995):788-791.
[9]. Janeway CA, Jr, Medzhitov R. Innate immune recognition. Annu Rev Immunol,2002, 20:197-216.
[10]. Moreno PR, Purushothaman KR, Sirol M, et al. Neovascularization in human atherosclerosis. Circulation,2006,113 (18):2245-2252.
[11]. Patel VA, Zhang QJ, Siddle K, et al. Defect in insulin-like growth factor-1 survival mechanism in atherosclerotic plaque-derived vascular smooth muscle cells is mediated by reduced surface binding and signaling. Circ Res,2001,88 (9):895-902.
[12]. Moreau M, Brocheriou I, Petit L, et al. Interleukin-8 mediates downregulation of tissue inhibitor of metalloproteinase-1 expression in cholesterol-loaded human macrophages:relevance to stability of atherosclerotic plaque. Circulation,1999,99 (3):420-426.
[13]. Ambrose JA. In search of the "vulnerable plaque":can it be localized and will focal regional therapy ever be an option for cardiac prevention? J Am Coll Cardiol,2008, 51 (16):1539-1542.
[14]. Corti R, Fuster V, Badimon JJ. Pathogenetic concepts of acute coronary syndromes. J Am Coll Cardiol,2003,41 (4):7S-14S.
[15]. Ridker PM, Buring JE, Rifai N. Soluble P-selectin and the risk of future cardiovascular events. Circulation,2001,103 (4):491-495.
[16]. Pradhan AD, Rifai N, Ridker PM. Soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and the development of symptomatic peripheral arterial disease in men. Circulation,2002,106 (7):820-825.
[17]. Ridker PM, Rifai N, Stampfer MJ, et al. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation,2000, 101 (15):1767-1772.
[18]. Ridker PM, Rifai N, Pfeffer M, et al. Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction. Circulation, 2000,101 (18):2149-2153.
[19]. Blankenberg S, Tiret L, Bickel C, et al. Interleukin-18 is a strong predictor of cardiovascular death in stable and unstable angina. Circulation,2002,106 (1):24-30.
[20]. Kolodgie FD, Virmani R, Burke AP, et al. Pathologic assessment of the vulnerable human coronary plaque. Heart,2004,90 (12):1385-1391.
[21]. Virmani R, Kolodgie FD, Burke AP, et al. Lessons from sudden coronary death:a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol,2000,20 (5):1262-1275.
[22]. Moulton KS, Vakili K, Zurakowski D, et al. Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis. Proc Natl Acad Sci USA,2003,100 (8):4736-4741..
[23]. Moulton KS, Heller E, Konerding MA, et al. Angiogenesis inhibitor endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. Circulation,1999,99:1726-1732.
[24]. Pels K, Labinaz M, O'Brien ER. Arterial wall neovascularization - potential role in atherosclerosis and restenosis. Jpn Circ J,1997,61 (11):893-904.
[25]. Bank AJ, Versluis A, Dodge SM, et al. Atherosclerotic plaque rupture:a fatigue process? Med Hypotheses,2000,55 (6):480-484.
[26]. Moreno PR, Purushothaman KR, Fuster V, et al. Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta:implications for plaque vulnerability, Circulation,2004,110 (14):2032-2038.
[27]. Kolodgie, F.D., et al., Intraplaque hemorrhage and progression of coronary atheroma. N Engl J Med,2003.349 (24):2316-2325.
[28]. Langheinrich AC, Kampschulte M, Buch T, et al. Vasa vasorum and atherosclerosis-Quid novi? Thromb Haemost,2007,97 (6):873-879.
[29]. Rosenzweig A. Endothelial progenitor cells.N Engl J Med,2003,348 (7):581-582.
[30]. Simons M. Angiogenesis:where do we stand now? Circulation,2005,111 (12):1556-1566.
[31]. Williams JK, Armstrong ML, Heistad DD. Vasa vasorum in atherosclerotic coronary arteries:responses to vasoactive stimuli and regression of atherosclerosis. Circ Res, 1988,62 (3):515-523.
[32]. Kolodgie FD, Gold HK, Burke AP, et al. Intraplaque hemorrhage and progression of coronary atheroma. N Engl J Med,2003,349 (24):2316-2325.
[33]. Brownlee. Biochemistry and molecular cell biology of diabetic complications. Nature, 2001,414 (6865):813-820.
[34]. Graversen JH, Madsen M, Moestrup SK. CD 163:a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma.Int J Biochem Cell Biol,2002,34 (4):309-314.
[35]. Moreno PR, Purushothaman KR, Purushothaman M, et al. Haptoglobin genotype is a major determinant of the amount of iron in the human atherosclerotic plaque. J Am Coll Cardiol.2008,52 (13):1049-1051.
[36]. Levy AP, Roguin A, Hochberg I, et al. Haptoglobin phenotype and vascular complications in patients with diabetes. N Engl J MED,2000,343 (13):969-970.
[37]. Touboul PJ, Hernandez-Hernandez R, Kucukoglu S, et al. Carotid artery intima media thickness, plaque and Framingham cardiovascular score in Asia, Africa/Middle East and Latin America:the PARC-AALA study. Int J Cardiovasc Imaging,2007,23 (5): 557-567.
[38]. Lorenz MW, Markus HS, Bots ML, et al. Prediction of clinical cardiovascular events with carotid intima-media thickness:a systematic review and meta-analysis. Circulation,2007,115 (4):459-467.
[39]. Prati P, Tosetto A, Vanuzzo D, et al. Carotid intima media thickness and plaques can predict the occurrence of ischemic cerebrovascular events. Stroke,2008,39 (9):2470-2476.
[40]. Coll B, Feinstein SB. Carotid intima-media thickness measurements:techniques and clinical relevance. Curr Atheroscler Rep,2008,10 (5):444-450.
[41]. Jager KA, Staub D. Did you measure the intima-media thickness? Ultraschall Med, 200930 (5):434-437.
. [42]. Chambless LE, Folsom AR, Clegg LX, et al. Carotid wall thickness is predictive of incident clinical stroke:the Atherosclerosis Risk in Communities (ARIC) study. Am J Epidemiol,2000,151 (5):478-487.
[43]. Gronholdt ML, Nordestgaard BG, Bentzon J, et al. Macrophages are associated with lipid-rich carotid artery plaques, echolucency on B-mode imaging, and elevated plasma lipid levels. J Vasc Surg,2002,35 (1):137-145.
[44]. Coli S, Magnoni M, Sangiorgi G, et al. Contrast-enhanced ultrasound imaging in intraplaque neovascularization in carotid arteries:correlation with histology and plaque echogenicity. J Am Coll Cardiol,2008,52 (3):223-230.
[45]. Staub D, Partovi S, Schinkel AF, et al. Correlation of carotid artery atherosclerotic lesion echogenicity and severity at standard US with intraplaque neovascularization detected at contrast-enhanced US. Radiology.2011,258 (2):618-626.
[46]. Xiong L, Deng YB, Zhu Y, et al. Correlation of carotid plaque neovascularization detected by using contrast-enhanced US with clinical symptoms. Radiology,2009, 251 (2):583-589.
[47].周巧兰,李治安,勇强,等.超声二维应变成像技术评价颈动脉粥样硬化斑块力学状态的初步研究.心肺血管病杂志,2010,29(4)：287-290.
[48].朱英,邓又斌,毕小军,等.超声二维应变技术评价动脉粥样硬化颈动脉壁弹性.中国医学影像技术,2008,24(9)：1379-1381.
[49]. Kerwin WS, O'Brien KD, Ferguson MS, et al. Inflammation in carotid atherosclerotic plaque:a dynamic contrast-enhanced MR imaging study. Radiology,2006,241 (2): 459-468.
[50]. Baker KP, Katsafados MG, Chatzopoulos DN, et al. Inflammatory markers and plaque morphology:an optical coherence tomography study. Int J Cardiol,2012,154 (3):287-292.
[51]. Tabas I. Macrophage death and defective inflammation resolution in atherosclerosis. Nat Rev Immunol,2010,10 (1):36-46.
[52]. Winter PM, Morawski AM, Caruthers SD, et al. Molecular imaging of angiogenesis in early-stage atherosclerosis with alpha (v) beta3-integrin-targeted nanoparticles. Circulation,2003,108 (18):2270-2274.
[53]. Tabas I. Pulling down the plug on atherosclerosis:finding the culprit in your heart. Nat MED,2011,17 (7):791-793.
[54]. Kolodgie F D, Narula J, Haider N, et al. Apoptosis in atherosclerosis. Does it contribute to plaque instability? Cardiol Clin,2001,19 (1):127-139.
[55]. Gao T, Zhang Z, Yu W,et al. Atherosclerotic carotid vulnerable plaque and subsequent stroke:a high-resolution MRI study. Cerebrovasc Dis,2009,27 (4): 345-352.
[56]. Derksen WJ, Peeters W, van Lammeren GW, et al. Different stages of intraplaque hemorrhage are associated with different plaque phenotypes:a large histopathological study in 794 carotid and 276 femoral endarterectomy specimens. Atherosclerosis, 2011,218 (2):369-377.
[57]. Ouimet T, Lancelot E, Hyafil F, et al. Molecular and cellular targets of the MRI contrast agent p947 for atherosclerosis imaging. Mol Pharm,2012,9 (4):850-861.
[58]. Lancelot E, Amirbekian V, Brigger I, et al. Evaluation of matrix metalloproteinases in atherosclerosis using a novel noninvasive imaging approach. Arterioscler Thromb Vase Biol,2008,28 (3):425-432.
[59]. Bazeli R, Coutard M, Duport BD,et al. In vivo evaluation of a new magnetic resonance imaging contrast agent (P947) to target matrix metalloproteinases in expanding experimental abdominal aortic aneurysms. Invest Radiol,2010,45 (10): 662-668.
[60]. Johnson JL, George SJ, Newby AC, et al. Divergent effects of matrix metalloproteinases 3,7,9, and 12 on atherosclerotic plaque stability in mouse brachiocephalic arteries. Proc Natl Acad Sci USA,2005,102 (43):15575-15580.
[61]. Loftus IM, Naylor AR, Bell PR, et al. Matrix metalloproteinases and atherosclerotic plaque instability. Br J Surg,2002,89 (6):680-694.
[62]. Vengrenyuk Y, Cardoso L, Weinbaum S. Micro-CT based analysis of a new paradigm for vulnerable plaque rupture:cellular microcalcifications in fibrous caps. Mol Cell Biomech,2008,5(1):37-47.
[63]. Vengrenyuk Y, Carlier S, Xanthos S, et al. A hypothesis for vulnerable plaque rupture due to stress-induced debonding around cellular microcalcifications in thin fibrous caps. Proc Natl Acad Sci USA,2006,103 (40):14678-14683.
[64]. Slager CJ, Wentzel JJ, Gijsen FJ, et al. The role of shear stress in the generation of rupture-prone vulnerable plaques. Nat Clin Pract Cardiovasc Med,2005,2 (8): 401-407.
[65]. Bennett MR. Life and death in the atherosclerotic plaque. Curr Opin Lipidol,2010,21 (5):422-426.
[66]. Schoenenberger AW, Urbanek N, Bergner M, et al. Associations of reactive hyperemia index and intravascular ultrasound-assessed coronary plaque morphology in patients with coronary artery disease. Am J Cardiol,2012,109 (12):1711-1716.
[67]. Tabas I. Macrophage apoptosis in atherosclerosis:consequences on plaque progression and the role of endoplasmic reticulum stress. Antioxid Redox Signal, 2009,11 (9):2333-2339.
[68]. Van Vre EA, Ait-Oufella H, Tedgui A, et al. Apoptotic cell death and efferocytosis in atherosclerosis. Arterioscler Thromb Vasc Biol,2012,32(4):887-893.
[69]. Schrijvers DM, De Meyer GR, Kockx MM, et al. Phagocytosis of apoptotic cells by macrophages is impaired in atherosclerosis. Arterioscler Thromb Vasc Biol,2005,25 (6):1256-1261.
[70]. Thorp E, Tabas I. Mechanisms and consequences of efferocytosis in advanced atherosclerosis. J Leukoc Biol,2009,86 (5):1089-1095.
[71]. Snow M, Ben-Sassi A, Winter RK, et al. Can carotid ultrasound predict plaque histopathology? Cardiovasc Surg (Torino),2007,48 (3):299-303.
[72]. Barry MJ, Richardson PD, Woolf N, et a 1. Accuracy of B-mode ultrasonography in detecting carotid plaque hemorrhage and ulceration. J Ann Va sc Surg,1990,4 (5):466-470.
[73]. Feinstein SB. Contrast ultrasound imaging of the carotid artery vasa vasorum and atherosclerotic plaque neovascularization. J Am Coll Cardiol,2006,48 (2):236-243.
[74]. Shalhoub J, Owen DR, Gauthier T, et al. The use of contrast enhanced ultrasound in carotid arterial disease. Eur J Vasc Endovasc Surg,2010,39:381-387.
[75]. Staub D, Patel MB, Tibrewala A, et al. Vasa vasorum and plaque neovascularization on contrast-enhanced carotid ultrasound imaging correlates with cardiovascular disease and past cardiovascular events. Stroke,2010,41 (1):41-47.
[76]. Staub D, Partovi S, Schinkel AF, et al. Correlation of carotid artery atherosclerotic lesion echogenicity and severity at standard US with intraplaque neovascularization detected at contrast-enhanced US. Radiology,2011,258 (2):618-626.
[77]. Feinstein SB, Coll B, Staub D, et al. Contrast enhanced ultrasound imaging. J Nucl Cardio12010,17 (1):106-115.
[78]. Vicenzini E, Giannoni MF, Puccinelli F, et al. Detection of carotid adventitial vasa vasorum and plaque vascularization with ultrasound cadence contrast pulse sequencing technique and echo-contrast agent. Stroke,2007,38 (10):2841-2843.
[79]. Clevert DA, Sommer WH, Helck A, et al. Improved carotid atherosclerotic plaques imaging with contrast-enhanced ultrasound (CEUS). Clin Hemorheol Microcirc,2011, 48(1):141-148.
[80]. Huang PT, Huang FG, Zou CP, et al. Contrast-enhanced sonographic characteristics of neovascularization in carotid atherosclerotic plaques. J Clin Ultrasound,2008,36 (6):346-351.
[81]. Schinkel AF, Krueger CG, Tellez A, et al. Contrast-enhanced ultrasound for imaging vasa vasorum:comparison with histopathology in a swine model of atherosclerosis. Eur J Echocardiogr.2010,11 (8):659-664.
[82]. Shah F, Balan P, Weinberg M, et al. Contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization:new surrogate marker of atherosclerosis? Vasc Med,2007,12 (4):291-297.
[83]. Giannoni MF, Vicenzini E, Citone M, et al. Contrast carotid ultrasound for the detection of unstable plaques with neoangiogenesis:a pilot study. Eur J Vasc Endovasc Surg,2009,37 (6):722-727.
[84].张莹,黄品同,杨琰,等.超声造影对脑梗死患者颈动脉粥样斑块的评价.中国超声医学杂志.2009,25(1)：16-19.
[85]. Clevert DA, Sommer WH, Helck A, et al. Improved carotid atherosclerotic plaques imaging with contrast-enhanced ultrasound (CEUS). Clin Hemorheol Microcirc,2011, 48 (1):141-148.
[86].何文.颈动脉斑块内新生血管的研究现状.中国卒中杂志,2009,4(7)：585-589.
[87]. Fleiner M, Kummer M, Mirlacher M, et al. Arterial neovascularization and inflammation in vulnerable patients:early and late signs of symptomatic atherosclerosis. Circulation,2004,110 (18):2843-2850.
[88].魏立亚,何文,张红霞,等.缺血性卒中患者颈动脉硬化斑块内新生血管的超声造影研究.中国卒中杂志,2009,4(11)：898-902.
[89].熊莉,邓又斌,毕小军,等.超声造影评价颈动脉粥样斑块稳定性.中华超声影像学杂志,2008,17(3)：214-216.
[90]. Faggioli GL, Pini R, Mauro R, et al. Identification of carotid'vulnerable plaque' by contrast-enhanced ultrasonography:correlation with plaque histology, symptoms and cerebral computed tomography. Eur J Vasc Endovasc Surg,2011,41 (2):238-248.
[91]. Tian J, Hu S, Sun Y, et al. Vasa vasorum and plaque progression, and responses to atorvastatin in rabbit model of atherosclerosis:contrast-enhanced ultrasound imaging and intravascular ultrasound study. Heart,2013,99 (1):48-54.
[92]. Jain RK, Finn AV, Kolodgie FD, et al. Antiangiogenic therapy for normalization of atherosclerotic plaque vasculature:a potential strategy for plaque stabilization. Nat Clin Pract Cardiovasc Med,2007,4 (9):491-450.
[93]. Tanaka H, Zaima N, Sasaki T, et al. Adventitial vasa vasorum arteriosclerosis in abdominal aortic aneurysm. PLoS One,2013,8 (2):p. e57398.
[94]. Macura KJ, Corl FM, Fishman EK, et al. Pathogenesis in acute aortic syndromes: aortic dissection, intramural hematoma, and penetrating atherosclerotic aortic ulcer. AJR Am J Roentgenol,2003,181 (2):309-316.
[95]. Coady MA, Rizzo JA, Elefteriades JA. Rizzo, et al. Pathologic variants of thoracic aortic dissections. Penetrating atherosclerotic ulcers and intramural hematomas. Cardiol Clin,1999,17 (4):637-657.
[96]. Scotlan d RS, Vallance PJT, Ahlu walia A. Endogenous factors involved in regulation of tone of arterial Vasa vasorum:implications for conduit vessel physiology. Cardiovasc Res,2000,46 (3):403-411.
[97]. Sacks AH. The vasa vasorum as a link between hypertension and arteriosclerosis. Angiology,1975,26:385-390.
[98]. Nakamura K, Onitsuka T, Yano M, et al. Clinical analysis of acute type A intramural hematoma:comparison between two different pathophysiological types. Ann Thorac Surg,2006.81 (5):1587-1592.
[99]. Baikoussis NG, Apostolakis EE. Penetrating atherosclerotic ulcer of the thoracic aorta: diagnosis and treatment. Hellenic J Cardiol,2010,51 (2):153-157.
[100]. Kwon HM, Sangiorgi G, Ritman EL, et al. Adventitial vasa vasorum in balloon-injured coronary arteries:visualization and quantitation by a microscopic three-dimensional computed tomography technique. J Am Coll Cardiol,1998.32 (7): 2072-2079.
[101]. Feinstein SB. The powerful microbubble:from bench to bedside, from intravascular indicator to therapeutic delivery system, and beyond. Am J Physiol Heart Circ Physiol, 2004,287 (2):H450-457.
[102]. Magnoni M, Coli S, Marrocco-Trischitta MM, et al. Contrast-enhanced ultrasound imaging of periadventitial vasa vasorum in human carotid arteries. Eur J Echocardiogr. 2009,10 (2):260-264.
[103], Staub D, Schinkel AF, Coll B, et al. Contrast-enhanced ultrasound imaging of the vasa vasorum:from early atherosclerosis to the identification of unstable plaques. JACC Cardiovasc Imaging,2010,3 (7):761-771.
[104]. Lee SC, Carr CL, Davidson BP, et al. Temporal characterization of the functional density of the vasa vasorum by contrast-enhanced ultrasonography maximum intensity projection imaging. JACC Cardiovasc Imaging,2010,3 (12):1265-1272.
[105]. Moguillansky D, Leng X, Carson A, et al. Quantification of plaque neovascularization using contrast ultrasound:a histologic validation. Eur Heart J,2011,32 (5):646-653.
[106]. Goertz DE, Frijlink ME, Krams R. et al. Vasa vasorum and molecular imaging of atherosclerotic plaques using nonlinear contrast intravascular ultrasound. Neth Heart J, 2007,15 (2):77-80.
[107]. Goertz DE, Frijlink ME, de Jong N, et al. Nonlinear intravascular ultrasound contrast imaging. Ultrasound Med Biol,2006,32 (4):491-502.
[108]. Carlier S, Kakadiaris IA, Dib N, et al. Vasa vasorum imaging:a new window to the clinical detection of vulnerable atherosclerotic plaques. Curr Atheroscler Rep,2005,7 (2):164-169.
[109]. Vavuranakis M, Papaioannou TG, Kakadiaris IA, et al. Detection of perivascular blood flow in vivo by contrast-enhanced intracoronary ultrasonography and image analysis:an animal study. Clin Exp Pharmacol Physiol,2007,34 (12):1319-1323.
[110]. Vavuranakis M, Kakadiaris IA, O'Malley SM, et al. A new method for assessment of plaque vulnerability based on vasa vasorum imaging by using contrast-enhanced intravascular ultrasound and differential image analysis. Int J Cardiol,2008,130 (1): 23-29.
[111]. O'Malley SM, Vavuranakis M, Naghavi M, et al. Intravascular ultrasound-based imaging of vasa vasorum for the detection of vulnerable atherosclerotic plaque. Med Image Comput Comput Assist Interv,2005,8 (Pt 1):343-351.
[112]. Vander Steen AF, Baldewsing RA, Levent Degertekin F, et al. IVUS beyond the horizon. EuroIntervention,2006,2(1):132-142.
[113]. Filipovic N, Teng Z, Radovic M, et al. Computer simulation of three-dimensional plaque formation and progression in the carotid artery. Med Biol Eng Comput,2013 Jan 25. [Epub ahead of print].
[114]. Busch M, Zernecke A. microRNAs in the regulation of dendritic cell functions in inflammation and atherosclerosis. J Mol Med (Berl),2012,90 (8):877-885.
[115]. Weber C, Noels H. Atherosclerosis:current pathogenesis and therapeutic options. Nat Med,2011,17 (11):1410-1422.
[116]. Blann AD, Nadar SK, Lip GY. The adhesion molecule P-selectin and cardiovascular disease. Eur Heart J,2003,24 (24):2166-2179.
[117].Weller GE, Lu E, Csikari MM, et al. Ultrasound imaging of acute cardiac transplant rejection with microbubbles targeted tointercellular adhesion molecule-1. Circulation, 2003,108 (2):218-224.
[118]. Bachmann C, Klibanov AL, Olson TS, et al. Targeting mucosal addressin cellular adhesion molecule (MAdCAM)-1 to noninvasively image experimental Crohn's disease. Gastroenterology,2006,130 (1):8-16.
[119]. Liu H, Wang X, Tan KB, et al. Molecular imaging of vulnerable plaques in rabbits using contrast-enhanced ultrasound targeting to vascular endothelial growth factor receptor-2. J Clin Ultrasound,2011,39 (2):83-90.
[120]. Lu Y, Wei J, Shao Q, et al. Assessment of atherosclerotic plaques in the rabbit abdominal aorta with interleukin-8 monoclonal antibody-targeted ultrasound microbubbles. Mol Biol Rep,2013,40 (4):3083-3092.
[121]. Hamilton AJ, Huang SL, Warnick D, et al. Intravascular ultrasound molecular imaging of atheroma components in vivo. J Am Coll Cardiol,2004,43 (3):453-460.
[122]. Kaufmann BA, Sanders JM, Davis C, et al. Molecular imaging of inflammation in atherosclerosis with targeted ultrasound detection of vascular cell adhesion molecule-1. Circulation,2007,116 (3):276-284.
[123]. Kaufinann BA, Carr CL, Belcik JT, et al. Molecular imaging of the initial inflammatory response in atherosclerosis:implications for early detection of disease. Arterioscler Thromb Vasc Biol,2010,30 (1):54-59.
[124]. Caplan ES, Khangura J, Bullens S, et al. Molecular imaging of the initial inflammatory response in atherosclerosis:implications for early detection of disease. Arterioscler Thromb Vasc Biol,2010,30 (1):54-59.
[125]. Behm CZ, Kaufmann BA, Carr C, et al. Molecular imaging of endothelial vascular cell adhesion molecule-1 expression and inflammatory cell recruitment during vasculogenesis and ischemia-mediated arteriogenesis. Circulation,2008,117 (22): 2902-2911.
[126]. Wu J, Leong-Poi H, Bin J, et al. Efficacy of contrast-enhanced US and magnetic microbubbles targeted to vascular cell adhesion molecule-1 for molecular imaging of atherosclerosis. Radiology,2011,260 (2):463-471..
[127]. Klibanov AL, Rychak JJ, Yang WC, et al. Targeted ultrasound contrast agent for molecular imaging of inflammation in high-shear flow. Contrast Media Mol Imaging, 2006,1 (6):259-266.
[128]. Ferrante EA, Pickard JE, Rychak J, et al. Dual targeting improves microbubble contrast agent adhesion to VCAM-1 and P-selectin under flow. J Control Release, 2009,140 (2):100-107.
[129]. Warram JM, Sorace AG, Saini R, et al. A triple-targeted ultrasound contrast agent provides improved localization to tumor vasculature. J Ultrasound Med,2011,30 (7): 921-931.