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超声造影在妇科疾病诊断中的应用研究

【作者】 刘真真

【导师】 姜玉新; 戴晴; 蔡胜;

【作者基本信息】 中国协和医科大学 , 影像医学与核医学, 2008, 博士

【摘要】 第一部分子宫病变超声造影和病理学对照研究目的观察子宫良恶性病变的实时灰阶超声造影增强特点,评价其临床应用价值。分析子宫内膜癌时间—强度曲线特征并进行病理学对照研究。资料和方法采用低机械指数脉冲反相谐波超声造影技术,对子宫良恶性病变61例进行观察,并取同期因子宫以外妇科病变而行超声造影检查的6个病例,观察正常子宮的造影增强特征。观察病变的超声造影灌注时相(包括增强和洗出两相)和增强模式,病变的灌注时相以子宫肌层作参照;病变的增强模式分为向心型、离心型、弥漫型和环状增强型。选择造影切面固定的子宮内膜癌病例,应用QLAB软件分别以病灶和未受累肌层为感兴趣区做时间—强度曲线,配对比较二者曲线参数的差异。将病例按厚度等分为两组,比较病灶曲线参数的差异。检验病灶的曲线参数与肿瘤分级、分期的相关性。对其中部分病例的标本切片进行免疫组化CD31染色,计数微血管密度,比较曲线参数与之的相关性。结果1、61例子宫病变包括子宫内膜癌30例(均于诊刮病理确诊后进行)、子宫肌瘤17例、子宫内膜息肉4例、滋养细胞肿瘤7例、子宫腺肌症2例和宫角妊娠清宫后残留1例。(1)子宮内膜癌中80%(24/30)病灶及向病灶供血的肌层增强早于未受累肌层,增强模式92.3%(28/30)为弥漫型;53.3%(16/30)病灶早于肌层退出,其余病例(46.7%)与肌层同步退出。76.7%(23/30)的病例显示了病灶的滋养血管;36.7%(11/30)的病例在癌生长部位、形态和范围等方面显示较常规超声更加清晰。(2)子宫肌壁间和粘膜下肌瘤80%(8/10)增强与肌层同步;子宫肌瘤中弥漫型增强模式占58.8%(10/17),向心型增强占35.3%(6/17);86.7%(13/15)早于肌层洗出.(3)子宫内膜息肉晚于肌层增强和洗出者占75%(3/4),离心型增强模式占75%(3/4)。(4)不典型滋养细胞肿瘤71.4%(5/7)与肌层同步增强,环状增强模式占85.7%(6/7),晚于肌层退出占85.7%(6/7)。(5)宫角妊娠清宫后残留1例,早于肌层增强和洗出,呈弥漫型增强,增强范围大于常规超声。2、时间—强度曲线参数比较显示:病灶较未受累肌层相比,增强开始时间、达峰时间早,达峰强度、增强强度大,增强速率快,差异有显著性(P<0.05)。1.9cm为病灶厚度的中位数,<1.9cm组与≥1.9cm组病灶的曲线参数无显著性差异。曲线参数在不同分化组和不同分级组之间差异无显著性。病灶的曲线上升时间和达峰时间与癌微血管密度呈负相关(P<0.05)。结论子宫各类病变的超声造影灌注时相和增强形态各有特点,能够提供较常规超声更加丰富的诊断信息;为病变的诊断和鉴别诊断提供了帮助。病灶和未受累肌层的时间强度曲线参数存在显著差异,子宫内膜癌病灶的时间强度曲线参数与癌微血管密度存在相关性.第二部分盆腔附件区病变实时灰阶超声造影研究目的观察盆腔附件区病变实时灰阶超声造影的增强形态和时间—强度曲线特征,评价超声造影对于鉴别病变良恶性的价值。资料和方法1、造影增强模式研究:应用低机械指数实时灰阶谐波超声造影技术对盆腔附件区病变进行超声造影观察。根据病变常规超声形态将其分为5大类:①单房囊性;②多房囊性;③单房囊实性;④多房囊实性;⑤实性。以达峰时病变的形态为增强形态,将其分为5类,分类的名称与常规超声相同。比较良恶性病变的常规超声形态分类与超声造影增强形态分类,将单房囊性和多房囊性增强形态合并为无实性增强组;将单房囊实性、多房囊实性和实性增强形态合并为有实性增强组。比较良恶性病变在有实性增强成分组和无实性增强成分组分布有无差异。分别根据常规超声和超声造影增强特征判断病变良恶性,计算各自的诊断效率并比较有无显著差异,进行ROC曲线分析。列举对诊断有帮助病例的超声造影表现。2、造影时间—强度曲线分析:从含有实性增强成分的病变中选择造影切面固定的病例进行分析。通过QLAB造影分析软件获得时间—强度曲线。将曲线下降支形态分为单相和双相两种;由曲线获得各个时间、强度和曲线下面积等参数。比较良恶性病变组之间曲线下降支形态以及各个曲线参数有无差异。结果1、共有76例盆腔病变纳入本研究,其中良性49例、恶性27例。造影增强形态分类与常规超声形态分组发生变化的占%(/);良恶性病变在有实性成分组和无实性成分组的分布有显著差异。根据常规超声和造影增强形态判断病变良恶性的准确率分别为81.6%和90.8%,差异无显著性.ROC曲线下面积分别为0.832和0.904。2、共35例病变进入时间—强度曲线研究。下降支形态单相组中恶性病变占93.3%(14/15);双相组中良性病变占65%(13/20),差异有显著性(P<0.05)。根据曲线下降支呈单相提示恶性病变的诊断特异性为92.9%,高于同组造影增强形态判断(75%)。曲线形态判断良恶性与造影增强形态的ROC曲线下面积分别为0.798和0.845。曲线参数中,恶性组半洗出时间和半廓清时间显著大于良性组(P<0.05)。结论附件区良恶性病变的超声造影增强形态有显著差异。超声造影增强形态能够反映病变内部血流分布情况及其丰富程度,为盆腔附件区良恶性病变的诊断和鉴别诊断提供更加可靠而准确的信息。良恶性病变的时间—强度曲线下降支形态以及曲线参数存在显著差异。

【Abstract】 Part One Contrast-enhanced Ultrasound of uterus diseases and a Correlation Study in PathologyPurposeObserve the contrast enhancement appearances of uterine diseases and assess the clinical value of contrast-enhanced ultrasound(CEUS) for these diseases.Analyze the characters of time-intensity curve(TIC) of endometrial cancers and the pathological basis of endometrial cancer TIC characteristics.Materials and methodsThe technique was low medical index pulse inversion harmonics and the contrast agent was SonoVue.Take 6 normal uterus CEUS as comparison cases.The enhancement phases and patterns were observed.The enhancement phases of lesions were campared to the uterus myometrium.The enhancement patterns were divided into four types: centripetal enhancement,centrifugal enhancement,diffuse enhancement and ring-like enhancement.In 18 cases,the time-intensity curves were given and the curve parameters were compared between the endometrial lesions and un-involved myometrium.Divide the cases into two groups by anterior-posterior width of lesions with value of 2cm.The curve parameters were compared between the two groups.In pathological study,efforts were paid on finding the relations between the grades or stages and tumor TIC parameters. Through immuno-histochemical staining for CD31 in 14 cases,the micro-vessel densities (MVD) were obtained.The relationships between TIC characters and MVDs were analyzed.Results1.Altogether 61 lesions were enrolled in this study,observed for their enhancement appearances during CEUS,including 30 endometrial carcinomas(confirmed by dilation and curettage,D&C),17 myomas,4 endometrial polyps,7 atypical trophoblastic tumors, 2 adenometriosis lesions and 1 uterus corner pregnancy remnant.(1) 80%endometrial cancer lesions and their feeding vessels enhanced earlier than the un-involved myometrium.The enhancement pattern was mainly diffuse type(92.3%, 28/30).53.3%(16/30) of cases wash-out earlier than the myometrium.The remain cases (46.7%) wash-out as the same pace as the myometrium.76.7%(23/30) cases showed the feeding vessels through CEUS.36.7%(11/30) of cases showed clearer tumors in growth positions,shapes and boundaries.(2) Submucous myomas and intra-myometrium myomas enhanced as the same pace as the myometrium(80%,8/10).The enhancement patterns were mainly diffuse enhancement(58.8%,10/17) and centripetal enhancement(35.3%,6/17).86.7% (13/15) of cases washed out earlier than the myometrium.(3) 75%(3/4) of polyps enhanced in a centrifugal enhancement and washed out later than the myometrium.(4) 71.4%(5/7) of atypical trophoblastic tumors lesions enhanced as the same pace as the myometrium but washed out later than myometrium.85.7%(6/7) were in ring-like pattern.(5) The one uterus corner pregnancy remnant enhanced earlier and washed out later than the myometrium in a diffuse type.The size became larger in enhancement state for about 1 cm diameter.2.The curve parameters analysis showed that the start time and peak time of lesions were earlier,the peak intensity and the rising of intensity were bigger,the rate of rising of intensity was faster in tumors than un-involved myometrium with significant differences. The curve parameters between<1.9cm group lesion and≥1.9cm group lesion have no significant difference,neither in different grade groups and in different stage groups.The rising time and peak time were negatively correlated with MVDs.ConclusionUterine diseases have showed different enhancement characters including the enhancement phase and patterns.CEUS is valuable for diagnosis and differentiation of these diseases.The TIC parameters of uterine cancer have relationship with the MVD of carcinoma. Part Two Pilot study of real-time gray-scale contrast-enhanced ultrasound in evaluation of pelvic lesionsPurposeObserve the enhancement patterns and time-intensity curve characters of pelvic lesions except of uterus using contrast-enhanced ultrasound(CEUS).Assess the value of CEUS in differentiation of benign and malignant lesions.Materials and methods1.Contrast agent was SonoVue.The technique was low medical index real-time gray scale harmonics contrast-enhanced ultrasound.The tumors were divided by routine ultrasonography into 5 types:①mono-cystic lesion;②multi-cystic lesion;③mono-cystic and solid lesion;④poly-cystic and solid lesion;⑤solid lesion.The peak intensity statuses of the lesions were named enhancement patterns,which were divided into the same named-patterns.The differences between the routine ultrasound and enhancement patterns were compared.We tried to find out the differences of enhancement patterns of benign and malignant lesions.The differentiation diagnoses of benign and malignant lesions were performed through routine ultrasonography with gray and colorful ultrasonography and contrast-enhanced ultrasound.The diagnostic efficiencies were calculated and ROC curves were given.The helpful cases which CEUS were useful for diagnosis were listed.2.Time-intensity curve(TIC) analysis.The lesions which contain solid enhancement parts were chosen into this analysis.It was commanded there was not any movement between the lesions and probes.In software QLAB,TICs were given taken the solid parts as the regions of interest(ROIs).The curve shapes were analysed and the kinetic parameters of TIC were compared between benign and malignant lesions.Results1.76 pelvic lesions,including 49 benign and 27 malignant cases,were recruild in this study.There was significant difference between benign and malignant tumors number in solid and cystic group.The accuracies of three methods in differentiation of benign and malignant lesions were 81.6%and 90.8%separately.The areas under the ROC curves (AUCs) were 0.832 and 0.904.CEUS were helpful in diagnosis of ovarian fibromas, ovary adenomyosis cysts,ovary metastatus cancers and lymphoma metastatus.2.35 lesions were recuilded.The shapes of the descending part of curves were divided into two groups:mono-phased and hi-phased.93.3%of mono-phased curves were malignant,65%of bi-phased curves were benign.The diagnose specificity of malignant tumors according to the shapes of curves reach to 92.9%which was higher than the combination of CEUS(75%).The areas under the ROC curves of them were 0.798 and 0.845 separately.The parameters of benign and malignant groups also showed significant differences.The half wash-out time and half eliminate time were lower in benign group than in the other one.ConclusionsBenign and malignant of pelvic lesions have shown significant differences in enhancement patterns,shape and the parameters of time-intensity curves.CEUS can reflect the blood distribution and its richness degree which provide richful information as for the differentiation between benign and malignant adnexal tumors.

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