颈动脉粥样硬化斑块易损性的超声造影研究
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摘要
颈内动脉（Internal carotid artery，ICA）粥样硬化是引起缺血性脑血管病的重要的病理基础。ICA狭窄不稳定动脉斑块破裂，继发血栓形成或者破溃形成栓塞，是患者发生脑血管事件及致死的重要原因，因此准确的判定斑块的稳定性对预防脑梗死的发生有着至关重要的意义。有研究发现，斑块内新生血管形成可以诱发斑块内出血和斑块破裂,与斑块的易损性密切相关，因此对斑块内新生血管化的评估越来越受到人们的关注。超声造影（contrast-enhanced ultrasound，CEUS）技术可通过增强血流及组织回声的对比来判断斑块内新生血管的情况，因此被用来评价斑块的易损性。本研究利用这一先进的超声造影技术分析斑块内新生血管化的程度，并结合微栓子监测（microembolic signals，MESs）技术及头部核磁共振（magneticresonance imaging,MRI)，进一步明确易损斑块的特征，探讨超声造影是否可以作为一种判定颈动脉斑块易损性的工具，为颈动脉狭窄患者的个体化治疗提供有价值的依据。本研究共分以下4部分：
第一部分ICA狭窄斑块的易损性与斑块内新生血管化程度的相关性研究
目的：探讨ICA狭窄斑块易损性与斑块内新生血管化程度的相关性。方法：选择33例有症状、13例无症状ICA粥样硬化性狭窄患者（狭窄程度≥50%），应用CEUS技术对ICA狭窄斑块进行检测，通过微泡造影剂增强显示新生血管，运用ACQ软件在机分析量化，增强的强度以分贝（decibel enhancement，db-E）为单位，比较两组患者的斑块内新生血管增强的程度。结果：有症状组斑块增强的例数及增强强度（22.76±1.95）明显高于无症状组（14.99±2.18），差异有统计学意义（P<0.01)；同组间（有症状组或无症状组）比较斑块内造影剂达峰值时间（Time to peak intensity，TPI）均迟于颈动脉，差异有统计学意义（P<0.01）；不同组别相同部位（斑块内或颈动脉管腔）的造影剂达峰值时间差异无统计学意义（P>0.05）。结论：CEUS可显示斑块内新生血管；有症状组ICA狭窄斑块新生血管化程度高于无症状组；CEUS可以根据斑块内造影剂增强强度评价斑块的易损性。
第二部分ICA狭窄斑块性质与微栓子信号关系的研究
目的：探讨ICA狭窄斑块的新生血管和回声性质与微栓子信号的关系。方法：选择46例ICA狭窄患者（狭窄程度≥50%），应用TCD进行MESs监测，应用CEUS及彩色多普勒超声（Color Doppler ultrasonography，CDUS）分析斑块内新生血管、斑块的回声性质与MESs数据的相关性。结果：CEUS检测共有30例患者在ICA狭窄斑块内检测到新生血管（65.2%）；有新生血管组MESs发生率（50%）明显高于无新生血管组（12.5%），P=0.023。CDUS检测斑块内回声性质与MESs的发生率两者没有明显相关性，P=0.237。结论：存在新生血管的ICA狭窄斑块MESs发生率更高。CEUS在评估斑块易损性方面优于CDUS。
第三部分ICA狭窄斑块易损性与缺血性脑血管事件关系的研究
目的：探讨ICA狭窄斑块的易损性与缺血性脑血管事件的相关性。方法：选择32例ICA狭窄患者（狭窄程度≥50%），应用CEUS检测ICA狭窄斑块内新生血管，同时行头MRI检查，分析斑块新生血管与狭窄同侧梗死灶的相关性。结果：MRI显示同侧梗死灶的患者ICA狭窄斑块内增强强度较无梗死灶组明显增高（23.31±1.83比16.62±3.07，P<0.01）。结论：CEUS显示的ICA狭窄斑块内新生血管化的程度与同侧大脑缺血事件发生密切相关。
第四部分超声造影与常规超声对ICA亚闭塞诊断价值的研究
目的：比较CEUS与CDUS对ICA亚闭塞的诊断价值。方法：选择53例经CDUS检查（采用凸阵探头与线阵探头联合应用的方法）颈动脉狭窄（≥70%）的患者，行CEUS检查，比较二者的结果。结果：53例患者经CDUS检查，55条血管存在重度以上狭窄，其中7支诊断为闭塞（12.7%），5支诊断为亚闭塞（9.1%），43条存在重度狭窄（78.2%），与超声造影结果完全一致。结论：CDUS与CEUS在诊断ICA亚闭塞方面有较高的一致性。
Internal carotid artery (ICA) atherosclerosis is an important pathologicalbasis of the ischemic cerebrovascular disease. Unstable carotid plaque ruptureand thrombosis embolism is the important reason for the occurrence ofcerebrovascular events and death, so the accurate identification of the plaquesvulnerability to prevent the occurrence of cerebral infarction is extremelysignificant. Studies have suggested that plaque neovascularization can inducethe hemorrhage and rupture and be associated with plaque vulnerabilityclosely.There has been a growing body of interest in the assessment of plaqueneovascularization.Contrast-enhanced ultrasound (CEUS) technology canidentify plaque neovascularization by enhancing echo contrast between theblood flow and the tissue, and is used to evaluate the vulnerability of the plaques.In this study we analysised the degree of the plaque neovascularization useingCEUS technology combined with microembolic signals (MESs) monitoringtechnology and magnetic resonance imaging(MRI),to characterize thevulnerable ICA atherosclerotic plaques,and to prove the CEUS technique is apotentially promising noninvasive tool that can be used in stratifying strokerisk in patients with ICA atherosclerotic disease.
Part one The study of the correlation between ICA plaque vulnerabilityand plaque neovascularization
Objective: The aim of this study was to compare the plaqueneovascularization properties between symptoms and asymptomatic ICAatherosclerotic stenosis using CEUS technique. Methods:CEUS were acquiredin33patients with symptomatic and13patients with asymptomatic ICA atherosclerotic stenosis (≥50%).,Contrast microbubbles detected within theplaque indicated neovascularisation and were quantified by decibel enhancement(dB-E) using the ACQ analysis software in the machine, the results of ICAplaques on CEUS were compared between the two groups. Results: In46patients, dB-E was significantly greater in symptomatic (22.76±1.95) vs.asymptomatic (14.99±2.18) patients (P<0.01). In the same group the arrival time(AT) and the time to peak intensity(TPI) have significantly difference indifferent position (P<0.01), and did not have significantly difference in the sameposition of different group (P>0.05).Conclusion: Different density ofintraplaque nevascularization in carotid arteries were observed betweensymptomatic and asymptomatic ICA stenosis. The real-time CEUS can observethe neovascularization within carotid atherosclerotic plaque non-invasively andquantitatively and can be used to assess the plaque vulnerability.
Part Two An assessment of the vulnerability of carotid plaques: acomparative study of intraplaque neovascularization and plaqueechogenicity
Objective: The aim of this study was to compare CEUS and CDUS in theassessment of plaque vulnerability using transcranial color Doppler (TCD)monitoring of microembolic signals (MES) as a reference technique. Methods: Atotal of46subjects with arterial stenosis (≥50%) underwent a carotid duplexultrasound, TCD monitoring of MES and CEUS (SonoVue doses of2.0mL)within a span of3days. The agreement between the CEUS, CDUS, and MESfindings was assessed with a chi-square test. A p-value less than0.05wasconsidered statistically significant.Results: Neovascularization was observed in30lesions (65.2%). The vascular risk factors for stroke were similar and therewere no age or gender differences between the2groups. Using CEUS, MES wereidentified in2patients (12.5%) within class1(non-neovascularization) as opposed to15patients (50.0%) within class2(neovascularization)(P=0.023).CDUS revealed no significant differences in the appearance of the MES betweenthe2groups (hyperechoic and hypoechoic)(P=0.237). Conclusion: MESs wereobserved more frequently in the neovascularization group detected by CEUS.CEUS may be better in identifying plaque vulnerability than CDUS.
Part three The study of plaque neovascularization by contrast-enhancedultrasound: Correlation with the ipsilateral infarcts
Objective: The aim of this study was to compare the correlation betweenthe plaque neovascularization properties and ipsilateral infarcts of the ICAatherosclerotic stenosis using MRI.Methods: A total of32patients withICA stenosis (≥50%)underwent CEUS and MRI.The results of ICAplaques on CEUS and the MRI were compared. Results: The ipsilateral lesionsof the ICA atherosclerotic stenosis at MRI were correlated with higher dB-E(23.31±1.83vs.16.62±3.07, P<0.01) plaques. Conclusion: The plaqueneovascularization degree showed a high correlation with the ipsilateral brainischemia event.
Part four The study of the diagnostic concordance between colourDoppler ultrasonography and contrast-enhanced ultrasound in assessingcarotid artery near-occlusion(NO)
Objective: The aim of this study was to evaluate the diagnostic concordancebetween colour Doppler ultrasonography and contrast-enhanced ultrasound inassessing carotid artery occlusion and NO.Methods: A total of53consecutivepatients with internal carotid artery (ICA) disease，who were diagnosed severestenosis（≥70%）by CDUS（Combining the linear array and the convexarray）,all the53patients were performed CEUS. The results of CEUS andCDUS were compared.Results: In53patients,55vessels were investigated byCDUS, all these vessels were underwent by CEUS for analysis. In these vessels 43of55(78.2%)were diagnosed severe stenosis,7of55(12.7%)were diagnosedocclusion and5of55(9.1%) NO by CDUS.All the Results agree with CEUS.NOvessels diagnosed occlusion by CDUS while diagnosed NO byCEUS.Conclusion: CDUS and CEUS indicateD a high concordance in theappreciation of carotid artery occlusion or subtotal occlusions.
第一部分ICA狭窄斑块的易损性与斑块内新生血管化程度的相关性研究
目的：探讨ICA狭窄斑块易损性与斑块内新生血管化程度的相关性。方法：选择33例有症状、13例无症状ICA粥样硬化性狭窄患者（狭窄程度≥50%），应用CEUS技术对ICA狭窄斑块进行检测，通过微泡造影剂增强显示新生血管，运用ACQ软件在机分析量化，增强的强度以分贝（decibel enhancement，db-E）为单位，比较两组患者的斑块内新生血管增强的程度。结果：有症状组斑块增强的例数及增强强度（22.76±1.95）明显高于无症状组（14.99±2.18），差异有统计学意义（P<0.01)；同组间（有症状组或无症状组）比较斑块内造影剂达峰值时间（Time to peak intensity，TPI）均迟于颈动脉，差异有统计学意义（P<0.01）；不同组别相同部位（斑块内或颈动脉管腔）的造影剂达峰值时间差异无统计学意义（P>0.05）。结论：CEUS可显示斑块内新生血管；有症状组ICA狭窄斑块新生血管化程度高于无症状组；CEUS可以根据斑块内造影剂增强强度评价斑块的易损性。
第二部分ICA狭窄斑块性质与微栓子信号关系的研究
目的：探讨ICA狭窄斑块的新生血管和回声性质与微栓子信号的关系。方法：选择46例ICA狭窄患者（狭窄程度≥50%），应用TCD进行MESs监测，应用CEUS及彩色多普勒超声（Color Doppler ultrasonography，CDUS）分析斑块内新生血管、斑块的回声性质与MESs数据的相关性。结果：CEUS检测共有30例患者在ICA狭窄斑块内检测到新生血管（65.2%）；有新生血管组MESs发生率（50%）明显高于无新生血管组（12.5%），P=0.023。CDUS检测斑块内回声性质与MESs的发生率两者没有明显相关性，P=0.237。结论：存在新生血管的ICA狭窄斑块MESs发生率更高。CEUS在评估斑块易损性方面优于CDUS。
第三部分ICA狭窄斑块易损性与缺血性脑血管事件关系的研究
目的：探讨ICA狭窄斑块的易损性与缺血性脑血管事件的相关性。方法：选择32例ICA狭窄患者（狭窄程度≥50%），应用CEUS检测ICA狭窄斑块内新生血管，同时行头MRI检查，分析斑块新生血管与狭窄同侧梗死灶的相关性。结果：MRI显示同侧梗死灶的患者ICA狭窄斑块内增强强度较无梗死灶组明显增高（23.31±1.83比16.62±3.07，P<0.01）。结论：CEUS显示的ICA狭窄斑块内新生血管化的程度与同侧大脑缺血事件发生密切相关。
第四部分超声造影与常规超声对ICA亚闭塞诊断价值的研究
目的：比较CEUS与CDUS对ICA亚闭塞的诊断价值。方法：选择53例经CDUS检查（采用凸阵探头与线阵探头联合应用的方法）颈动脉狭窄（≥70%）的患者，行CEUS检查，比较二者的结果。结果：53例患者经CDUS检查，55条血管存在重度以上狭窄，其中7支诊断为闭塞（12.7%），5支诊断为亚闭塞（9.1%），43条存在重度狭窄（78.2%），与超声造影结果完全一致。结论：CDUS与CEUS在诊断ICA亚闭塞方面有较高的一致性。
Internal carotid artery (ICA) atherosclerosis is an important pathologicalbasis of the ischemic cerebrovascular disease. Unstable carotid plaque ruptureand thrombosis embolism is the important reason for the occurrence ofcerebrovascular events and death, so the accurate identification of the plaquesvulnerability to prevent the occurrence of cerebral infarction is extremelysignificant. Studies have suggested that plaque neovascularization can inducethe hemorrhage and rupture and be associated with plaque vulnerabilityclosely.There has been a growing body of interest in the assessment of plaqueneovascularization.Contrast-enhanced ultrasound (CEUS) technology canidentify plaque neovascularization by enhancing echo contrast between theblood flow and the tissue, and is used to evaluate the vulnerability of the plaques.In this study we analysised the degree of the plaque neovascularization useingCEUS technology combined with microembolic signals (MESs) monitoringtechnology and magnetic resonance imaging(MRI),to characterize thevulnerable ICA atherosclerotic plaques,and to prove the CEUS technique is apotentially promising noninvasive tool that can be used in stratifying strokerisk in patients with ICA atherosclerotic disease.
Part one The study of the correlation between ICA plaque vulnerabilityand plaque neovascularization
Objective: The aim of this study was to compare the plaqueneovascularization properties between symptoms and asymptomatic ICAatherosclerotic stenosis using CEUS technique. Methods:CEUS were acquiredin33patients with symptomatic and13patients with asymptomatic ICA atherosclerotic stenosis (≥50%).,Contrast microbubbles detected within theplaque indicated neovascularisation and were quantified by decibel enhancement(dB-E) using the ACQ analysis software in the machine, the results of ICAplaques on CEUS were compared between the two groups. Results: In46patients, dB-E was significantly greater in symptomatic (22.76±1.95) vs.asymptomatic (14.99±2.18) patients (P<0.01). In the same group the arrival time(AT) and the time to peak intensity(TPI) have significantly difference indifferent position (P<0.01), and did not have significantly difference in the sameposition of different group (P>0.05).Conclusion: Different density ofintraplaque nevascularization in carotid arteries were observed betweensymptomatic and asymptomatic ICA stenosis. The real-time CEUS can observethe neovascularization within carotid atherosclerotic plaque non-invasively andquantitatively and can be used to assess the plaque vulnerability.
Part Two An assessment of the vulnerability of carotid plaques: acomparative study of intraplaque neovascularization and plaqueechogenicity
Objective: The aim of this study was to compare CEUS and CDUS in theassessment of plaque vulnerability using transcranial color Doppler (TCD)monitoring of microembolic signals (MES) as a reference technique. Methods: Atotal of46subjects with arterial stenosis (≥50%) underwent a carotid duplexultrasound, TCD monitoring of MES and CEUS (SonoVue doses of2.0mL)within a span of3days. The agreement between the CEUS, CDUS, and MESfindings was assessed with a chi-square test. A p-value less than0.05wasconsidered statistically significant.Results: Neovascularization was observed in30lesions (65.2%). The vascular risk factors for stroke were similar and therewere no age or gender differences between the2groups. Using CEUS, MES wereidentified in2patients (12.5%) within class1(non-neovascularization) as opposed to15patients (50.0%) within class2(neovascularization)(P=0.023).CDUS revealed no significant differences in the appearance of the MES betweenthe2groups (hyperechoic and hypoechoic)(P=0.237). Conclusion: MESs wereobserved more frequently in the neovascularization group detected by CEUS.CEUS may be better in identifying plaque vulnerability than CDUS.
Part three The study of plaque neovascularization by contrast-enhancedultrasound: Correlation with the ipsilateral infarcts
Objective: The aim of this study was to compare the correlation betweenthe plaque neovascularization properties and ipsilateral infarcts of the ICAatherosclerotic stenosis using MRI.Methods: A total of32patients withICA stenosis (≥50%)underwent CEUS and MRI.The results of ICAplaques on CEUS and the MRI were compared. Results: The ipsilateral lesionsof the ICA atherosclerotic stenosis at MRI were correlated with higher dB-E(23.31±1.83vs.16.62±3.07, P<0.01) plaques. Conclusion: The plaqueneovascularization degree showed a high correlation with the ipsilateral brainischemia event.
Part four The study of the diagnostic concordance between colourDoppler ultrasonography and contrast-enhanced ultrasound in assessingcarotid artery near-occlusion(NO)
Objective: The aim of this study was to evaluate the diagnostic concordancebetween colour Doppler ultrasonography and contrast-enhanced ultrasound inassessing carotid artery occlusion and NO.Methods: A total of53consecutivepatients with internal carotid artery (ICA) disease，who were diagnosed severestenosis（≥70%）by CDUS（Combining the linear array and the convexarray）,all the53patients were performed CEUS. The results of CEUS andCDUS were compared.Results: In53patients,55vessels were investigated byCDUS, all these vessels were underwent by CEUS for analysis. In these vessels 43of55(78.2%)were diagnosed severe stenosis,7of55(12.7%)were diagnosedocclusion and5of55(9.1%) NO by CDUS.All the Results agree with CEUS.NOvessels diagnosed occlusion by CDUS while diagnosed NO byCEUS.Conclusion: CDUS and CEUS indicateD a high concordance in theappreciation of carotid artery occlusion or subtotal occlusions.
引文
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