【作者】 杨杰；

【导师】 李杰；

【作者基本信息】 山东大学 ， 影像医学与核医学， 2017， 硕士

【摘要】 研究背景近年来,临床工作中发现患有甲状腺结节的患者越来越多,有关甲状腺癌发病率的问题已成为研究热点,高频率超声诊断仪的应用在甲状腺疾病筛查和诊断中的作用愈发明显。据Cooper DS等国外学者研究,甲状腺结节的检查率高达67%,尤以女性多见,在检出结节中恶性结节占5%～10%,并有逐年增高的趋势。因此,甲状腺癌的临床检测显得尤为重要,需要做到尽早发现与确诊,并采取积极治疗措施,从而达到显著改善患者病情的效果。现在,超声检测(ultrasonography,USG)已经成为甲状腺结节的常规检测方法,其主要依赖常规二维超声、彩色多普勒超声进行诊断,但单纯以普通二维超声方法对甲状腺结节进行良恶性诊断时只可以从病灶边界状态、钙化程度、回声、纵横比等方面作为鉴别指标,其敏感性、特异性不高。近些年来随着超声检查技术地快速发展和超声弹性成像技术越来越被临床所接受,为鉴别甲状腺结节的良恶性增添了新的检查方法。弹性成像是对组织弹性状态的信息进行反馈的过程,可将其视为判断病变属性的关键指标。通过分析可知,病灶具有一定的生物学特性,这与组织弹性有密切的关系,当出现一般性的病理状况时,会导致组织弹性的变化,如恶性病变常引起弹性特征的变化,使组织硬度随之增大,从而增加组织弹性系数,这.是因为恶性病灶中通常包含一定的病变组织,其硬度非常高。除此之外,病变组织受浸润时,会不断生长,其边缘形状如同星星或者蟹足,和周边的结构有粘连。超声弹性成像(ultrasound elastography,UE)提供了组织硬度的图像,以图像形式来表现各组织的硬度情况,从而明显反映出各组织的不同硬度,以此作为判断组织良恶性的依据,该技术也逐渐成为了诊断良恶性甲状腺结节的新方法。在甲状腺超声弹性成像的应用方面按照不同激励方式可以将其分成如下几类:声辐射力脉冲弹性成像(acoustic radiation force impulse,ARFI)、压迫式弹性成像(compression elastography,CE)以及超声剪切波成像(supersonic shear-wave imaging,SSI),三者是目前使用最普遍的超声弹性成像技术,分别在甲状腺疾病的诊断中得到很好的应用。CE成像技术以静态方式实现,也可以将其称为弹性应变成像(strain elastography,SE),该成像技术在临床应用方面出现最早。CE技术的加压过程通过手持探头实现,从探头轴线方向对相应组织区域产生纵向压迫感,从而引起组织微小变形,并通过超声波监测跟踪变形状态,之后采用复合相关法分析变形组织在压缩前以及压缩后得到的回波信号,同时计算出组织中的应变/位移情况,最后通过伪彩或者灰阶将其编码为所需的图像。ARFI成像技术的原理是通过声辐射力对特定组织区域的硬度与弹性进行测试,属于动态弹性成像方式。ARFI技术利用超声聚焦方式,通过探头发射低频声波脉冲来测试感兴趣组织,当测试区域的组织接收到激励后其内部产生微小变形同时生成朝四周各个方向传播的剪切波,对提取到的回波信号进行分析得到测试区的组织变形程度或者剪切波传播(shear wave velocity,SWV),从而获得感兴趣组织反馈的弹性信息。ARFI技术包括了声触诊组织量化(virtual touch tissue quantification,VTQ)以及声触诊组织成像(virtual touch tissue imaging,VTI)这两项技术,其中,VTI技术对组织纵向压缩形成的位移反馈信息进行收集后,再通过灰阶编码图像表现组织硬度与弹性状态。其中,较暗区域代表此处组织的硬度比较大,亮度较大的区域则说明此处的组织硬度比较低。VTQ技术先收集组织的横向变形信息,之后再计算剪切波传播速度便可得到组织的硬度与弹性状态,该技术也被称为点剪切波成像技术(point shear wave elastography,point SWE)。通常而言,剪切波在较高硬度组织内具有相对更快的传播速率,反之当组织硬度较低时传播速率也较小。本研究主要采用VTI技术中的弹性面积比(elastic area radio,EAR)与应变率比(strain rate,SR)对甲状腺结节进行定量评价,两者的应用有助于甲状腺良恶性结节的鉴别诊断,在诊断甲状腺结节时,超声检查的价值会有更大的体现。尽管如此,因合并弥漫性病变的甲状腺结节,受到基础疾病的影响,会引发组织的病变,对临床诊断结果有一定的影响。在合并及未合并弥漫性病变的甲状腺结节诊断方面,上述两类超声弹性成像技术的应用标准并未一致,且两种弹性成像技术对甲状腺结节诊断价值的对比研究目前文献研究尚少。研究目的1.研究合并与未合并弥漫性病变的甲状腺结节的弹性情况,为甲状腺良恶性结节的鉴别诊断提供依据;2.比较声触诊组织成像(VTI)弹性面积比与应变率比对合并与未合并弥漫性病变的甲状腺结节的诊断价值。资料与方法1.1临床资料:选择2014年3～12月于本院就诊的疑似甲状腺结节患者72例(共84个结节),均经病理检查证实。选定的样本要具备:①结节都是实性的,或者实性占主导;②结节的直径为5～40mm;③结节内部不存在出现明显钙化、液化的区域。其中男性患者20人,女性患者52人;年龄最大者为65岁,最小者为32岁(45.1±9.6)岁。经病理证实可知,共有39个合并弥漫性病变结节(包含26个结节性甲状腺肿,13个合并桥本氏甲状腺炎),恶性结节和良性结节分别为22个和17个;共有45个未合并弥漫性病变结节,恶性结节和良性结节分别为30个和15个。2.仪器与方法对患者实施检查,运用的都是常规超声和内置VTI软件的超声诊断仪。使用的S2000超声诊断仪,由德国西门子研制,内置VTI软件,所用探头为9L4,其频率最小为4MHz,最大为9MHz。患者保持仰卧姿势,将颈部完全显露出来,保持均匀的呼吸状态,将增益、焦点和深度调到合适值,对患者的甲状腺结节的声像图特征进行细致观察,详细记录,将诊断仪调节到“EI”模式,将取样框设定为病灶范围的两到三倍。患者短暂停止呼吸,医生将探头置于患者病灶处,在质量分数大于等于60时,保存图像,挑选成像良好的VTI图像,通过ImageJ软件进行选取,将结节在常规二维超声成像和VTI成像的面积分别记录下来。此外,还要选取甲状腺组织当做参照物,其结节深度要相同,将结节的应变率记作A,尺寸、深度都相同的甲状腺组织的应变率记作B,所有的结节都要选取5帧可信图像,计算出均值。将显示的结节面积除以常规超声显示的结节面积,就可得到EAR;SR=B/A。3.统计学分析进行统计运用的是SPSS19.0软件。使用x±s表示计量资料,通过t检验进行比较;比较计数资料使用的是x2检验。通过绘制受试者工作特征(ROC)曲线评价EAR、SR对甲状腺结节的诊断效能,运用Z检验来比较曲线下面积(AUC)。P<0.05意味着差异有统计学意义。结果1.常规超声、EAR、SR对甲状腺结节的诊断结果:1.1运用常规超声波来诊断未合并弥漫性病变良恶性结节,其灵敏度为66.7%、特异度为 88.3%、准确率为 77.8%,EAR 依次是 73.3%、90.0%、84.4%,SR依次是80.0%、86.7%、84.4%。相对于常规超声,EAR、SR的灵敏度、特异度、准确率的P均<0.05;EAR特异度、灵敏度与SR比较,P均<0.05,二者准确率比较,P>0.05。1.2运用常规超声诊断合并弥漫性病变良恶性结节,其灵敏度为70.6%、特异度为 77.3%、准确率 74.4%,EAR 依次是 82.4%、81.8%、82.1%,SR 依次是 76.5%、86.4%、82.1%。相对于常规超声,EAR、SR的灵敏度、特异度、准确率的P均<0.05;EAR特异度、灵敏度和SR对比可知,P均<0.05,对比两者的准确率,P>0.05。1.3常规超声、EAR、SR对合并与未合并弥漫性病变良恶性结节诊断的特异度、准确率比较,P均<0.05。2.良恶性结节的EAR、SR比较2.1合并弥漫性病变组良性结节EAR明显低于恶性结节{(0.92±0.23).vs(1.33±0.13),P<0.05}、良性结节SR明显低于恶性结节{(3.05±1.17)vs(4.76±1.06),P<0.05};2.2未合并弥漫性病变组良性结节EAR亦明显低于恶性结节{(0.93±0.21)vs(1.30±0.17),P<0.05}、良性结节SR亦明显低于恶性结节{(3.77±2.40)vs(5.35±1.57),P<0.05}。3.EAR、SR对甲状腺结节的诊断效能EAR诊断合并弥漫性病变结节的截断值为1.06,诊断未合并弥漫性病变结节的截断值为0.89,两者的曲线下面积都是0.877,对比它们的曲线下面积,P>0.05。SR诊断合并弥漫性病变结节的截断值为3.48,诊断未合并弥漫性病变结节的截断值为3.62,两者的曲线下面积依次为0.869、0.772,对比它们的曲线下面积,P>0.05。结论对合并与未合并弥漫性病变甲状腺良恶性结节进行鉴别诊断,VTI弹性面积比及应变率比都有良好的效果,提高超声鉴别诊断甲状腺良恶性结节的灵敏度、特异度和准确率,但两者的鉴别诊断效能相差不大。在鉴别诊断甲状腺良恶性结节时,运用超声弹性成像技术,为临床诊断工作提供了新方法,显示出在甲状腺疾病临床诊断中的广阔前景。更多还原

【Abstract】 BackgroundIn the past few years,the increasing number of patients with thyroid nodules have been found in clinical work,which has become a research hotspot about the issue of incidence of thyroid cancer,and the function of application of high frequency ultrasound scanner to the screening of thyroid disease and diagnosis has been increasingly obvious.According to the research of Cooper DS and other foreign scholars,it is found that the detection rate of thyroid nodules is as high as 67%,especially common in women,which accounts for 5%～10%for the proportion of malignant nodules found in the detected nodules and there is a increasing trend of year by year.Therefore,the clinical detection of thyroid cancer is particularly important,and it is essential that thyroid cancer detected and made a definite diagnosis as early as possible as well as taken active treatment measures in order to achieve the effect of improving patients’ condition significantly.Now,ultrasonic testing(ultrasonography,USG)has become a routine detection of thyroid nodules,which mainly relies on the diagnosis of the conventional two-dimensional ultrasound and color Doppler ultrasound,but the sensitivity and specificity would not be high if we purely made a malignant and benign for thyroid nodules by two-dimensional ultrasound,which should result in the identification index only from the focal boundary state,the degree of calcification,echo,aspect ratio and so on.In recent years,with the rapid development of ultrasound detection technology and the increasing clinical acceptance of ultrasound elastography,new methods have been added to identify the benign and malignant thyroid nodules.Elastic imaging is the process of feedback on the information about the elastic state of tissue,which can be regarded as a key index to determine the attributes of lesions.The biological characteristics of tissue elasticity and lesion is closely related to the organization,usually elastic characteristics under pathological conditions will change,such as changes of malignant lesions often caused by elastic properties,the microstructure and hardness increased,thereby increasing tissue elasticity,and this is because that the lesions with high hardness generally exist in malignant lesions and these lesions also exist in infiltrating growth with characteristics of the edge of a star or crab like,and in the vicinity of structure adhesion.Ultrasound elastography(ultrasound elastography UE)provides images of tissue hardness and shows the hardness of various tissuesin the form of image,which clearly reflects the different hardness of the organization so as to judge the malignant and benign as the basis,and the technology has become a new method for diagnosis of benign and malignant thyroid nodules.The application of thyroid ultrasound elastography in accordance with different incentive methods can be divided into the following categories:acoustic radiation force impulse(acoustic radiation force impulse,ARFI),pressure(compression elastography,CE elastography)and ultrasonic shear wave imaging(supersonic shear-wave imaging,SSI),and they have been the most elastic imaging technologies commonly used and have achieved a good application in the diagnosis of thyroid disease.CE imaging technology is implemented in a static manner,or it can be called strain elastography(SE),appearing earliest in the clinical application about this imaging technique.The compression process of CE technology is achieved by hand-held probe and brings about the longitudinal compression sense to the corresponding tissue region from the probe axis,causing tissue deformation,and the deformation state of ultrasonic monitoring and tracking,using the relative analysis method of deformation in the composite tissue before compression and compression obtained after the echo signal,and calculating the strain or displacement of organization and encoding it for the desired image by pseudo color or gray scale.The principle of ARFI imaging is to test the stiffness and elasticity of a particular tissue around by means of sound radiation,which belongs to dynamic elastography.ARFI using ultrasonic focusing probe is by emitting low frequency acoustic pulses to test the tissue of interest,and when the test area of the organization receives the incentive of its internal micro deformation while generating shear wave toward the periphery spread in all directions,or degree of shear wave propagation analysis of deformation of the test section and the echo signal is extracted to the organization(shear wave velocity,SWV),so as to gain a sense of elastic interest organization feedback information.ARFI technology includes vtq(virtual touch tissue quantification,VTQ)and virtual touch tissue imaging(virtual touch tissue imaging,VTI)of the two technology,the VTI technology on Microstructure and formation of longitudinal compression displacement information feedback,and then through the performance of gray-scale image encoding tissue hardness and elastic state.The darker area represents the hardness of the tissue here,and the brightness of the region indicates that the hardness of the tissue here is low.VTQ technology is to collect the transverse deformation information of tissue firstly,then calculate the shear wave velocity that can be obtained by hardness and elastic tissue,which is also known as point shear wave imaging technology(point shear wave elastography,point SWE).Generally speaking,shear wave has a relatively fast propagation rate in higher hardness tissues,otherwise,when the tissue hardness is lower,the propagation rate is smaller.This research mainly uses the VTI technology in the elastic area ratio(elastic area radio,EAR)and strain rate ratio(strain rate SR)for quantitative evaluation of thyroid nodules,and the two applications are helpful to differential diagnosis of benign and malignant thyroid nodules,which can significantly improve the value of ultrasonography in diagnosis of thyroid nodules.However,the thyroid nodules is associated with diffuse lesions because of the basic diseases,which leads to parenchymal tissue changes and affects the clinical diagnosis.The above two kinds of ultrasound elastography currently comorbid with or without diffuse lesions of thyroid nodules is lack of uniform standards,and a comparative study of two of the value of elastography in the diagnosis of thyroid nodules in the literature is lack of study.Objectives1.This research aims to investigate the elasticity of thyroid nodules in patients combied with or without diffuse lesions,and to provide evidence for the differential diagnosis of benign and malignant thyroid nodules;2.This research aims to compare the diagnostic value of acoustic contrast tissue imaging(VTI),elastic area ratio,and strain rate ratio for thyroid nodules combined with or without diffuse lesions.Materials and Methods1.clinical data:To select 72 cases(84 nodules)of patients suspected thyroid nodules who were treated at our hospital from March to December in 2014,which are confirmed by pathological examination.Inclusion criteria:solid or solid nodules;the diameter of nodules is 5-40mm;and there are no gross calcification and large liquefaction areas in the nodules.There are 20 males and 52 females.The age was 32～65 years.Confirmed by pathological examination with diffuse lesions(39 nodules with Hashimoto’s thyroiditis,13 nodular goiter,26),including 17 benign and 22 malignant lesions;not with diffuse nodules in 45,including 15 benign and 30 malignant cases.2.instruments and methodsThe patients are examined with conventional ultrasound and an ultrasonic diagnostic instrument equipped with VTI software.Germany SIEMENS S2000 ultrasonic diagnostic instrument,equipped with VTI software,select 9L4 probe,probe frequency 4.09.0MHz.With the patient in the supine position,fully exposed the neck,asking the calm breathing,adjusting the gain,focus and depth to the appropriate conditions,the ultrasonographic features of thyroid nodules were observed and recorded,in "EI" mode,sampling frame focus range 2-3 times.Patients are required to hold breath,holding the probe contact location,when the mass fraction is less than 60,store images on VTI imaging using Image J software with image sketch and recording nodules on conventional two-dimensional ultrasound imaging and VTI in the area.The other pulmonary nodules in the same depth of thyroid tissue as the reference strain rate is marked nodule A,with the depth of the same size of normal thyroid tissue strain rate of each nodule marked B,5 frames from the trusted image,to take the average.EAR= showed a nodule area/conventional ultrasound showed the area of the nodule;SR = B/A.3.statistical analysisUsing SPSS19.0 statistical software.The measurement data is expressed by X士s,and t test is compratively used.X2 test is used to compare count data.Receiver operating characteristic(ROC)curve is drawn to evaluate the diagnostic efficacy of EAR and SR on thyroid nodules.The area under the curve(area,under,the,curve,AUC)is compared with Z test.The difference of P<0.05 is statistically significant.Results1.Diagonosis results of conventional ultrasound,EAR,SR for thyroid nodules:1.1 Conventional ultrasonography in diagnosis of benign and malignant lesions with diffuse nodules the sensitivity,specificity and accuracy are 66.7%,88.3%,77.8%,EAR are 73.3%,90%,84.4%,SR are 80%,86.7%,84.4%.The sensitivity,specificity and accuracy of EAR and SR are compared with those of conventional ultrasound.P(average)<0.05,EAR specificity,sensitivity is compared with SR,P(average)<0.05,and the accuracy rate of the two is P>0.05.1.2 Conventional ultrasound for diagnosis of benign and malignant lesions with diffuse nodules the sensitivity,specificity and accuracy are 70.6%,77.3%,74.4%,EAR are 82.4%,81.8%,82.1%,SR are 76.5%,86.4%,82.1%.The sensitivity,specificity and accuracy of EAR and SR are compared with those of conventional ultrasound.P(average)<0.05,EAR specificity,sensitivity is compared with SR,P(average)<0.05,and the accuracy rate of the two is P>0.05.1.3 The specificity and accuracy of conventional ultrasound,EAR and SR in the diagnosis of benign and malignant nodules of combined and non diffuse lesions are P,(average)<0.05.Comparison of EAR and SR in 2.benign and malignant nodules2.1 In the diffuse lesion group,the benign nodule EAR is significantly lower than the malignant nodule {(0.92 + 0.23)vs(1.33 + 0.13),P<0.05} and benign nodule SR is significantly lower than the malignant nodule {(3.05 + 1.17)vs(4.76 + 1.06),P<0.05};2.2 EAR With diffuse lesion group is obviously lower than that in benign nodules EAR with malignant nodules {(0.93 + 0.21)vs(1.30 + 0.17),P<0.05} SR is obviously lower than that in benign nodules,malignant nodules {(3.77 + 2.40)vs(5.35+ 1.57),P<0.05}.3.Diagnostic efficacy of EAR and SR in the diagnosis of thyroid nodules and diffuse lesions,with truncated nodules values are 1.06 and 0.89,the area under the curve is 0.877,two of the area under the curve comparison,P>0.05.The cutoff values of SR for the diagnosis of nodules with or without diffuse lesions are 3.48 and 3.62,respectively.The area under the curve is 0.869 and 0.772,respectively,and the area under the curve of the two is P>0.05.ConclusionsVTI elastic area ratio and strain rate are more effective than the two for differential diagnosis combined with and without diffuse lesions of benign and malignant thyroid nodules,improving the benign and malignant thyroid nodules ultrasound in differential diagnosis of sensitivity,specificity and accuracy,but the efficacy of differential diagnosis is similar.The differential diagnosis of benign and malignant thyroid nodules with ultrasound elastography provides a new method for clinical diagnosis and shows broad prospects in the clinical diagnosis of thyroid diseases.更多还原