甲状腺结节实时灰阶超声造影的临床研究

【作者】 张波；

【导师】 姜玉新；

【作者基本信息】 中国协和医科大学 ， 影像医学与核医学， 2007， 博士

【摘要】 目的1.观察甲状腺结节实时灰阶超声造影的增强形式及时间-强度曲线特征,并与常规超声进行比较。2.探讨超声造影对甲状腺良恶性结节的鉴别诊断价值。资料和方法对95例甲状腺结节患者共104个病灶进行超声造影研究。其中良性结节53个,恶性51个。超声造影剂为SonoVue,技术为低机械指数实时灰阶超声造影成像。从5方面观察甲状腺结节超声造影增强特征,包括增强边界、增强形态、增强水平、增强方向和增强面积。将超声造影增强模式分为5种类型:无增强、均匀增强、不均匀增强、区域增强和环状增强。脱机分析动态图像在病灶不同部位及周围实质生成时间-强度曲线。总结不同病理类型甲状腺结节的造影增强特点和增强模式,比较甲状腺结节不同部位及良恶性结节之间的时间-强度曲线参数,比较超声造影和常规超声的诊断敏感性、特异性、阳性预测值、阴性预测值。结果1.增强边界不清提示恶性的敏感性47%,特异性87%,阳性预测值77%,阴性预测值63%。2.增强形态不规则提示恶性的敏感性55%,特异性94%,阳性预测值90%,阴性预测值68%。3.增强面积大于50%提示恶性的敏感性84%,特异性42%,阳性预测值58%,阴性预测值73%。4.向心或离心性增强提示恶性的敏感性61%,特异性77%,阳性预测值72%,阴性预测值67%。5.非均匀增强提示恶性的敏感性31%,特异性98%,阳性预测值94%,阴性预测值60%。6.区域增强提示恶性的敏感性57%,特异性94%,阳性预测值91%,阴性预测值69%。7.环状增强提示良性的敏感性83%,特异性94%,阳性预测值94%,阴性预测值83%。8.多向+不规则廓清提示恶性的敏感性62%,特异性94%,阳性预测值94%,阴性预测值79%。9.恶性结节较良性结节微泡进入强度低、上升时间短,且恶性结节周围实质增强上升速率大于良性结节。10.超声造影结合灰阶及彩色多普勒诊断甲状腺结节的敏感性98.0%,特异性96.2%,高于常规超声。结论超声造影在甲状腺结节诊断和鉴别诊断中具有重要应用价值,超声造影结合灰阶及彩色多普勒的诊断敏感性、特异性均高于后两者单独应用或联合应用。目的探讨甲状腺结节实时灰阶超声造影增强形式及时间-强度曲线参数与CD34、CD105、VEGF、CK19和Ki67表达水平的关系。资料和方法采用低机械指数实时灰阶谐波超声造影技术,对62例甲状腺病人的62个结节进行超声造影,包括甲状腺乳头状癌30例,结甲27例,腺瘤4例,桥本病1例。术后石蜡标本行CD34、CD105、VEGF、CK19和K167免疫组织化学染色。比较甲状腺良恶性结节CD34、CD105、VEGF、CK19和K167表达水平,分析超声造影增强形式和时间-强度曲线各参数与CD34、CD105、VEGF、CK19和K167表达的关系。结果甲状腺乳头状癌结节的MVD和VEGF表达显著高于良性结节。恶性结节新生血管在肿瘤内分布不均衡,癌巢边缘MVD显著高于中心。标记肿瘤新生血管,CD105较CD34特异性更高。CD34与甲状腺乳头状癌结节增强边界不清、形态不规则、向心+离心增强、区域增强呈正相关。CD105与恶性结节的增强形式之间未发现有意义的相关性。VEGF与结节增强边界不清、增强形态不规则、向心+离心增强正相关,与环状增强负相关。CD34差值(边缘-中心)与边缘曲线上升速率和多向不规则廓清呈正相关。VEGF与结节边缘、中心、周围实质的进入时间、达峰时间、上升时间呈负相关。与结节边缘、中心、周围实质的增强速率、多向不规则廓清呈正相关。CK19与造影的增强方向、增强边界、增强形态、不均匀增强呈正相关;与均匀增强、环状增强呈负相关。结论1.甲状腺恶性结节的MVD和VEGF表达显著高于良性结节平均水平。2.甲状腺实时灰阶超声造影可以反映甲状腺结节血管生成情况,甲状腺结节超声造增强形式及时间-强度曲线参数与MVD、VEGF和CK19之间的多项参数存在相关性。更多还原

【Abstract】 PartⅠThe Research of Thyroid Nodules by Using Real-time Gray Contrast-enhanced Ultrasound Purpose1.To observe the enhancement pattern and time-intensity curve of thyroid nodules by using contrast-enhanced ultrasound,and compare with conventional ultrasound.2.To assess the value of contrast-enhanced ultrasound in differentiating thyroid benign and malignant nodule.Material and methodsNinety-five patients scheduled for surgical removal of the nodule were evaluated with real-time gray-scale contrast-enhanced ultrasound under a low mechanical index.The microbubble contrast agent was Sono Vue.Of the 104 lesions,53 lesions were benign,51 were malignant.The enhancement of the thyroid nodules were characterized from five aspects, including margin,shape,level,orientation and the proportion of enhancement.There are five patterns of enhancement,including non,homogenous,heterogeneous, regional and rim-like enhancement.Analyzing the off-line dynamic images to create the Time-intensity curves in different parts of the thyroid nodules.To analyze the enhancement findings of thyroid nodules with repect to the histological results.To compare time-intensity curves of different parts of the nodule and between benign and malignant nodules.In addition,the sensitivity,specificity,PPV(positive predictive value),NPV(negative predictive value) of the contrast-enhancement ultrasound were calculated and compared with conventional ultrasound.Results1.Unclear enhancement-margin was suggestive of malignant with a sensitivity/specificity/PPV/NPV of 47%/87%/77%/63%.2.Irregular enhancement-shape was suggestive of malignant with a sensitivity/specificity/PPV/NPV of 55%/94%/90%/68%.3.Enhancement-proportion＞50%was suggestive of malignant with a sensitivity/specificity/PPV/NPV of 84%/42%/58%/73%.4.Centripetal and Centrifugal enhancement was suggestive of malignant with a sensitivity/specificity/PPV/NPV of 61%/77%/72%/67%.5.heterogeneous enhancement was suggestive of malignant with a sensitivity/specificity/PPV/NPV of 31%/98%/94%/60%.6.Region enhancement was suggestive of malignant with a sensitivity/specificity/PPV/NPV of 57%/94%/91%/69%.7.Rim-like enhancement was suggestive of benign with a sensitivity/specificity/PPV/NPV of 83%/94%/94%/83%.8.Multiphase and irregular wash-out was suggestive of malignant with a sensitivity/specificity/PPV/NPV of 62%/94%/94%/79%.9.The baseline intensity signal was lower and the rising time was shorter in malignant than in benign nodule.The rate of rising of intensity signal in the parenchyma around malignant nodule was greater than in benign.10.With a sensitivity of 98.0%and a specificity of 96.2%,contrast-enhanced ultrasound combining conventional ultrasound is superior to conventional ultrasound.ConclusionsContrast-enhanced ultrasound is of great value in diagnosing and differentiating thyroid nodules.Combining conventional ultrasound with contrast-enhanced ultrasound is superior to conventional ultrasound. PartⅡExpression of CD34,CD105,VEGF,CK19 and Ki67 in thyroid nodules and correlation with Contrast-enhanced Ultrasound findings PurposeTo assess the correlation between the quantitative and qualitative imaging findings on contrast-enhanced ultrasound images and the intensity of CD34,CD105, VEGF,CK19 and Ki67 expression in thyroid nodules.Material and methodsSixty-two patients with 62 nodules were evaluated with real-time gray-scale contrast-enhanced ultrasound under a low mechanical index.The microbubble contrast agent was Sono Vue.Of the 62 lesions,30 lesions were thyroid papillary carcinoma,51were goiter,4 were adenoma,1 was Hashimoto’s thyroiditis.The paraffined specimens were selected for immunohistochemical staining for CD34, CD105,VEGF,CK19 and Ki67.Comparing the intensity of CD34,CD105,VEGF, CK19 and Ki67 expression between the benign and malignant nodules,correlating them with the characters and patterns of the enhancement of the thyroid nodules.ResultsHigher MVD and VEGF expression was noted in thyroid papillary carcinoma than benign nodules.Angiogenesis is more heterogeneous in malignant than benign nodules,MVD of the margin of the lesions is higher than center.CD105 is superior than CD34 in labeling the tumor newly formed vessel.Positive correlations have been found in CD34 and unclear enhancing margin, irregular enhancing shape,centreipetal and centrifugal enhancement and reigional enhancement.No correlation was found between CD105 and the findings of the enhancement.Positive correlations have been found in VEGF and unclear enhancing margin,irregular enhancing shape,centreipetal and centrifugal enhancement,a negative correlation has been found between VEGF and rim-like enhancement.The difference of CD34 between the margin and center is positively correlated with the rising rate of the margin and multi-phase and irregular wash-out.Negative correlations have been found in VEGF and arrival time,peak time, rising time of nodule and around parenchyma.Positive correlations have been found between VEGF and rising rate,multi-phase and irregular wash-out of nodule.Positive correlations have been found in CK19 and unclear enhancing margin, irregular enhancing shape,centreipetal and centrifugal enhancement and heterogeneous enhancement.Negtive correlations have been found in CK19 and homogeneous enhancement and rim-like enhancement.Conclusion1.MVD and VEGF expression was noted higher in thyroid papillary carcinoma than benign nodules.2.Contrast-enhanced ultrasound is of great value in assessing angiogenesis in thyroid nodules.There are correlations between MVD、VEGF和CK19 and contrast enhanced ultrasound findings.更多还原