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中华医学超声杂志（电子版）

中华医学超声杂志（电子版） ›› 2017, Vol. 14 ›› Issue (04) : 274 -279. doi: 10.3877/cma.j.issn.1672-6448.2017.04.008

所属专题： 文献；

浅表器官超声影像学

甲状腺乳头状癌超声造影特征与微血管密度及微血管面积的相关性研究
种静1, 孙咏梅1,†(), 宁春平1, 王宏桥1, 杨宗利1, 董海1   
  1. 1. 266003　青岛大学附属医院超声科
  • 收稿日期:2016-11-23 出版日期:2017-04-01
  • 通信作者: 孙咏梅
  • 基金资助:
    国家自然科学基金(81501477)

Contrast-enhanced ultrasound characteristics of papillary thyroid carcinoma and its relationship with microvessel density and microvessel area

Jing Chong1, Yongmei Sun1,†(), Chunping Ning1, Hongqiao Wang1, Zongli Yang1, Hai Dong1   

  1. 1. Department of Ultrasound, the Affiliated Hospital of Qingdao University, Qingdao 266003, China
  • Received:2016-11-23 Published:2017-04-01
  • Corresponding author: Yongmei Sun
  • About author:
    Corresponding author: Sun Yongmei, Email:
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引用本文：

种静, 孙咏梅, 宁春平, 王宏桥, 杨宗利, 董海. 甲状腺乳头状癌超声造影特征与微血管密度及微血管面积的相关性研究[J]. 中华医学超声杂志（电子版）, 2017, 14(04): 274-279.

Jing Chong, Yongmei Sun, Chunping Ning, Hongqiao Wang, Zongli Yang, Hai Dong. Contrast-enhanced ultrasound characteristics of papillary thyroid carcinoma and its relationship with microvessel density and microvessel area[J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2017, 14(04): 274-279.

目的

探讨甲状腺乳头状癌（PTC）超声造影血流灌注参数与微血管密度（MVD）及微血管面积（MVA）的相关性，评估超声造影无创性评价PTC血管生成的价值。

方法

选取2014年4月至2016年10月在青岛大学附属医院手术切除并经病理证实的PTC患者69例，按病灶大小将患者分为<1 cm组、1~2 cm组、>2.0 cm组，按颈部淋巴结病理结果将患者分为淋巴结转移组、未转移组。采用t检验（两组间）或单因素方差分析（多组间）比较各组超声造影血流灌注定量参数；对术后结节及甲状腺组织病理标本行免疫组化染色获取MVD及MVA，并与定量参数进行Spearman秩相关性分析。

结果

（1）PTC结节峰值强度（Peak）、曲线下面积（AUC）、MVD及MVA均低于周围正常甲状腺组织（14.95±4.96 vs 22.67±6.11，970.01±263.20 vs 1798.35±563.67，118.91±31.32 vs 206.27±39.58，8.58±2.68 vs 18.47±3.13），差异均有统计学意义（t=-8.700、-11.061、-14.377、-20.532，P均<0.05）；（2）随着PTC结节增大，各组Peak及AUC、MVD及MVA依次增加，且不同大小3组结节组间两两比较，差异均有统计学意义（<1 cm组与1~2 cm组比较：t=0.000、0.000、0.000、0.000；<1 cm组与>2.0 cm组比较：t=0.027、0.044、0.033、0.000；1~2 cm组与>2.0 cm比较：t=0.027、0.044、0.033、0.000，P均<0.05）；（3）淋巴结转移组Peak、AUC、MVD及MVA值高于未转移组（16.86±4.36 vs 13.80±3.55，1128.16±290.85 vs 874.39±192.27，114.12±30.69 vs 103.67±22.19，10.30±2.44 vs 7.54±2.29），差异均有统计学意义（t=3.177、4.366、6.336、4.742，P均<0.05）；（4）相关分析结果显示，Peak、AUC与MVD呈正相关（r=0.506、0.478，P均<0.05），Peak、AUC与MVA呈正相关（r=0.648、0.653，P均<0.05）；灌注参数TP、MTT与MVD与MVA无明显相关性。

结论

超声造影定量参数Peak、AUC在一定程度上可反映甲状腺乳头状癌的MVD与MVA，可无创性评价在体肿瘤微血管生成情况，对PTC的临床诊断及其预后的评估具有重要价值。

关键词: 甲状腺肿瘤, 超声检查, 微血管
Objective

To explore the correlation between quantitative parameters of blood perfusion with contrast-enhanced ultrasound (CEUS) and microvessel density (MVD), microvessel area (MVA) in papillary thyroid carcinoma (PTC). And to investigate the value of CEUS in evaluating the angiogenesis in PTC before operation.

Methods

Totally 69 cases of patients with papillary thyroid carcinoma were selected from April 2014 to October 2016 in the Affiliated Hospital of Qingdao University. The CEUS characteristics of 69 patients with papillary thyroid carcinoma confirmed by pathology were retrospectively analyzed. The patients were divided into three groups according to maximum diameter of lesions (<1 cm group, 1-2 cm group and >2.0 cm group), and two groups according to pathologic reports (neck lymph node metastatic and nonmetastatic groups). The blood perfusion parameters between or among different groups were evaluated by ″t″test or one-way ANOVA. Immunohistochemical staining were performed to evaluate the MVD, MVA in the surgical specimens, and the correlation of quantitative parameters with MVD, MVA were assessed by Spearman.

Results

(1) Peak Intensity (Peak), area under the curve (AUC), MVD and MVA of thyroid carcinoma were lower than the surrounding normal thyroid tissue (14.95±4.96 vs 22.67±6.11, 970.01±263.20 vs 1798.35±563.67, 118.91±31.32 vs 206.27±39.58, 8.58±2.68 vs 18.47±3.13), and the differences were statistically significant (t=-8.700, -11.061, -14.377 and -20.532, all P<0.05). (2)With the increase of the lesion′s maximum diameter, Peak, AUC, MVD and MVA increased, and the differences were statistically significant (t=0.000, 0.000, 0.000, 0.000; t=0.027, 0.044, 0.033, 0.000; t=0.027, 0.044, 0.033, 0.000, all P<0.05). (3) Papillary thyroid carcinoma with lymphatic involvement had significantly higher values of Peak, AUC, MVD and MVA than those without lymphatic involvement (16.86±4.36 vs 13.80±3.55, 1128.16±290.85 vs 874.39±192.27, 114.12±30.69 vs 103.67±22.19, 10.30±2.44 vs 7.54±2.29), and the differences were statistically significant (t=3.177, 4.366, 6.336 and 4.742, all P<0.05). (4) A positive correlation existed between the Peak, AUC and MVD, and the differences were statistically significant (r=0.506, 0.478, all P<0.05). Peak, AUC and MVA showed positive correlation, and the differences were statistically significant (r=0.648, 0.653, all P<0.05). TP, MTT and MVD, MVA showed no correlations (all P>0.05).

Conclusions

The values of Peak and AUC calculated from CEUS were correlated to MVD and MVA. CEUS may be used to evaluated the angiogenesis of PTC before operation. And CEUS is helpful for prediction of prognosis of PTC.

Key words: Thyroid neoplasms, Ultrasonography, Microvessels
表1 PTC患者结节与周围正常组织血流灌注参数及MVD、MVA比较（±s）
取样位置 个数 TP（s） MTT（s） Peak（%） AUC（%?s） MVD（条/HP） MVA（%）
PTC结节 69 43.69±17.92 62.14±18.10 14.95±4.96 970.01±263.20 118.91±31.32 8.58±2.68
正常组织 69 39.04±16.81 56.78±18.15 22.67±6.11 1798.35±563.67 206.27±39.58 18.47±3.13
t值 ? 1.571 1.735 -8.700 -11.061 -14.377 -20.532
P值 ? 0.118 0.085 <0.001 <0.001 <0.001 <0.001
表2 不同大小PTC患者结节血流灌注参数及MVD、MVA比较（±s）
肿瘤大小 个数 TP（s） MTT（s） Peak（%） AUC（%?s） MVD（条/HP） MVA（%）
<1 cm组 26 44.59±14.72 61.66±14.82 12.77±3.14ab 837.40±194.95ab 102.15±24.69ab 6.69±2.14ab
1~2 cm组 29 45.48±20.09 62.65±22.43 14.88±3.58c 960.46±206.13c 118.00±25.12c 9.03±2.14c
>2 cm组 14 37.24±19.25 61.99±14.32 19.16±3.71 1236.08±293.53 151.93±34.22 11.16±2.11
F值 ? 0.956 0.021 15.643 14.688 15.485 21.140
P值 ? 0.390 0.979 <0.001 <0.001 <0.001 <0.001
表3 不同淋巴结转移情况的PTC患者结节血流灌注参数及MVD、MVA比较（±s）
组别 例数 TP（s） MTT（s） Peak（%） AUC（%?s） MVD（条/HP） MVA（%）
淋巴结转移组 26 43.74±19.38 64.99±17.31 16.86±4.36 1128.16±290.85 144.12±30.69 10.30±2.44
淋巴结未转移组 43 43.66±17.21 60.41±18.55 13.80±3.55 874.39±192.27 103.67±22.19 7.54±2.29
t值 ? 0.016 1.020 3.177 4.366 6.336 4.742
P值 ? 0.987 0.312 0.002 <0.001 <0.001 <0.001
图1，2 甲状腺乳头状癌患者血流灌注特征。图1为与正常组织相比，甲状腺头状癌病灶增强达峰时呈不均匀性低增强；图2为时间-强度曲线，蓝色代表病灶，绿色代表甲状腺正常组织
图3，4 甲状腺乳头状癌患者CD34免疫组化染色组织病理图（SP ×200）。图3为血管内皮细胞被CD34染成棕色或棕黄色，分布不均匀；图4为Image-Pro Plus 6图像分析软件沿着色的微血管内皮自动半自动勾勒微血管腔，红色表示微血管覆盖区域（SP ×200）。
表4 PTC患者血流灌注参数与MVD、MVA的相关性
指标 MVD MVA
r值 P值 r值 P值
TP 0.046 0.708 -0.052 0.669
MTT 0.159 0.191 0.079 0.521
Peak 0.506 <0.001 0.648 <0.001
AUC 0.478 <0.001 0.653 <0.001
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