Correlation Study Between Contrast-enhanced Ultrasound Features And Microvascular Densities In Benign And Malignant Thyroid Nodules*

BackgroundThyroid nodule is a common clinical problem and the most common malignant thyroid nodules is papillary thyroid carcinoma(PTC),which has a good prognosis.Clinically,how to improve the preoperative differential diagnosis of thyroid nodules is the heated research topic.High-resolution ultrasound has been widely used in the diagnosis of thyroid nodules,by which the malignant risk of nodules could be evaluated by observing the location,size,number,cervical lymph node metastasis and tissue characteristics of nodules(such as echo,calcification,internal blood supply,etc).Because angiogenesis is related to the growth,hematogenous spread and metastasis of tumor cells,A common marker of angiogenesis,microvascular density(MVD),has been utilized for the quantification of intratumoral angiogenesis in tumor tissue in recent years.However,MVD in surgical and biopsy specimens is invasive and prone to sampling errors,so it is not suitable for preoperative evaluation.Therefore,it is very important to establish a non-invasive preoperative detection method that can be used repeatedly to detect the whole tumor.Relevant studies have reported that contrast-enhanced ultrasound(CEUS)could display the microcirculation of tumors and provide detailed information of tumor vascular distribution,so this technique could be used to detect and quantitatively evaluate the vascular characteristics of tumors.This study proposed by analyzing the enhancement pattern and quantitative parameters from the time-intensity curve of CEUS in three most common benign and malignant thyroid nodules,study the correlation between quantitative parameters of CEUS and MVD,it provides an effective method for the diagnosis and differential diagnosis of benign and malignant thyroid nodules,meanwhile,it also provides reliable pathologic basis for CEUS in differential diagnosis of benign and malignant thyroid nodules.PurposeOur aim is to analyze the enhancement pattern and quantitative parameters from the TIC of CEUS in three most common benign and malignant thyroid nodules,including PTC,thyroid adenoma and nodular goiter,study the correlation between MVD and quantitative parameters of CEUS,and thus to provide reliable pathologic basis for CEUS in differential diagnosis of benign and malignant thyroid nodules,and also to provide a non-invasive preoperative detection method about microvascular evaluation for thyroid nodules.Methods1.From August 2016 to September 2017,114 patients with 175 thyroid nodules(including 77 PTCs,29 thyroid adenomas and 69 nodular goiters)were examined with CEUS in Department of Ultrasound,First Affiliated Hospital of Army Medical University,and were retrospectively analyzed.Conventional ultrasound,CEUS enhancement patterns and TIC quantitative parameters of the nodules were analyzed,Quantitative parameters mainly include peak intensity(PI),area under the curve(AUC),arrival time(AT)and time to peak(TTP).All patients underwent surgical excision of nodules,and we obtained pathological results of all lesions.2.CD31 immunohistochemical staining were performed to count the MVD in the surgical specimens,and the correlation between quantitative parameters of CEUS and MVD were assessed.Results1.CEUS showed 82 malignant nodules and 93 benign nodules,while pathological results showed 77 PTCs,29 thyroid adenomas and 69 nodular goiters.CEUS image features displayed: most of PTCs were heterogeneous and low enhancement pattern,most of thyroid adenomas showed a high enhancement or peripheral annular enhancement pattern,and most of the nodular goiters showed an equal enhancement pattern.The accuracy,sensitivity and specificity of CEUS in diagnosis of PTC were 84.57%,85.71% and 83.67%,respectively.2.The peak intensity(PI)of PTC was lower than that of thyroid adenoma or nodular goiter and the difference was statistically significant(P<0.05),while there were no statistically significant differences in arrival time(AT),time to peak(TTP)and area under the curve(AUC)(P>0.05).Compared with the normal surrounding thyroid tissues,The PI and AUC of most PTC were lower than those of the normal surrounding thyroid tissues,and differences were statistically significant(P<0.05).The PI and AUC of most thyroid adenomas were higher than those of the normal surrounding thyroid tissues,and differences were statistically significant(P<0.05).The PI and AUC of most nodular goiters were not significantly different from the normal surrounding thyroid tissues.3.CD31 immunohistochemical staining were performed to analyze the average MVD counts of thyroid nodules of the three pathological types,PTC,nodular goiter and thyroid adenoma were respectively:(66.12±14.30),(89.8±6.67)and(121.67±25.61)vessels per high power field.The average MVD in PTC was significantly lower than that in thyroid adenoma or nodular goiter,the difference was statistically significant(P<0.05).A significantly positive correlation was observed between CEUS quantitative parameter PI and MVD in thyroid nodule(r=0.888,P <0.001),and a significantly positive correlation was observed between AUC and MVD(r=0.644,P<0.001).Conclusion1.Three common benign and malignant thyroid nodules have different CEUS characteristics.Of all,PTC mainly presents slow,heterogeneous and low enhancement pattern,while benign thyroid nodules are mainly characterized with fast,high or equal enhancement pattern.Conventional ultrasound combined with CEUS and quantitative analysis can improve the diagnostic accuracy of thyroid nodules.2.There were a significant positive correlation between CEUS quantitative parameters(PI and AUC)and MVD count.This study provides a non-invasive detection method for preoperative diagnosis of thyroid nodules.Preoperative CEUS provides a useful research basis and experimental basis for the effective evaluation of benign and malignant thyroid nodules.