DOI: https://doi.org/10.21203/rs.3.rs-2411669/v1
To explore the diagnostic value of qualitative and quantitative parameters of contrast-enhanced ultrasound (CEUS) for differentiating thyroid carcinoma nodules and benign thyroid nodules.
The qualitative and quantitative CEUS parameters of 290 thyroid nodules confirmed by pathology were analyzed retrospectively. The evaluation indexes included wash in, wash out, enhancement degree, enhancement homogeneity, morphology after angiography, and ring enhancement.
Malignant nodules had an unclear margin, uneven perfusion, and low perfusion (all p < 0.05). The internal peak of malignant nodules was lower than that of benign nodules, the TP at the outer edge of malignant nodules was higher than that of benign nodules, the sharpness at the outer edge of malignant nodules was lower than that of benign nodules, and the AUC at the outer edge of malignant nodules was lower than that of benign nodules (all p < 0.05). Multivariate analysis showed that internal peak and external sharpness were independent risk factors for the diagnosis of differentiated thyroid carcinoma and benign thyroid nodules.
The qualitative and quantitative analysis of CEUS can provide valuable information for the differential diagnosis of differentiated thyroid carcinoma (DTC) and benign thyroid nodules.
Thyroid cancer includes a heterogeneous group of tumors. Differentiated thyroid cancer (DTC) [1], which includes papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), and their variant subtypes [2], is the most frequent endocrine malignancy. DTC is an inert malignant tumor and the most rapidly increasing cancer diagnosis worldwide. Patients with DTC usually present with cervical lymph node metastasis and require surgery. In addition, iodine-131 and thyroid inhibitors have been shown to be beneficial for more than 85% of patients, improving their high-quality survival rate. Yet, approximately 15% of cases may have tumor biological variation due to gene mutation, resulting in different subtypes and poor prognosis, which may be related to the biological characteristics of highly invasive tumors [3]. Therefore, the differential diagnosis of the nature of thyroid nodules is still of great significance.
Contrast-enhanced ultrasound (CEUS) can evaluate microcirculation perfusion of tissues in real-time [4, 5], providing accurate and reliable data, and avoiding diagnostic errors caused by individual differences [6]. The normal thyroid tissue is rich in micro-vessels, so it shows rapid and uniform enhancement after administration of a contrast agent. However, the thyroid nodules have different angiogenesis patterns, so the manifestations of CEUS may be different [7]. Most previous CEUS studies were based on the interior of thyroid nodules [8–10]. However, CEUS enhancement patterns in thyroid nodules are still not sufficient to diagnose thyroid cancer [11]. So far, only a few studies have reported on the perfusion characteristics of the outer edge of the nodule.
The aim of this study was to analyze the value of qualitative and quantitative parameters of CEUS in the differential diagnosis of DTC.
A total of 274 patients with thyroid nodules who underwent surgery in our hospital between March 2017 and July 2021 were selected. Briefly, 290 nodules from 66 males and 208 females aged 20–81 years, with an average age of (47.9 ± 13.7) years, were examined. Inclusion criteria were: (1) those who signed the informed consent form for CEUS; (2) complete nodules could be simultaneously displayed in one ultrasound section; (3) the final surgical and pathological results were obtained. Exclusion criteria were the following: (1) CEUS showed no perfusion nodules; (2) CEUS image was not clear; (3) the distance between the edge of the nodule (> 50%) and the thyroid capsule was < 3 mm.
Esaote Mylab90 (Esaote, Genoa, Italy) color ultrasound instrument was used. Linear array probe LA523 with a frequency of 4 ~ 13MHz was used for conventional ultrasound, and LA522 with a frequency of 3 ~ MHz, mechanical index (MI) of 0.06, and direct sound pressure (DP) of 50kPa was used for gray-scale ultrasound contrast. The patient was placed in a supine position, fully exposing the neck. An ultrasonic biomedical couplant gel was then applied to a patient's skin to facilitate the transfer of ultrasound energy between a standard ultrasound instrument and the body. Then, a routine ultrasound examination was performed on the lesion, and the size (maximum diameter) of the thyroid nodule was recorded and the section with the most abundant blood flow was displayed by power Doppler in the longitudinal section as the CEUS observation section was selected. The CEUS imaging mode was used, and the 1.2ml SonoVue (Bracco, Italy) was then injected through the superficial vein of the elbow, followed by quick rinsing with 10.0ml normal saline.
The enhancement of the contrast agent in the nodule and surrounding normal thyroid tissues were then observed. The evaluation indexes included wash in, wash out, enhancement degree, enhancement homogeneity, morphology after angiography, ring enhancement. With respect to the surrounding thyroid parenchyma, the enhancement degree of the lesion was classified as hypo-enhancement, iso-enhancement, and hyper-enhancement. The enhancement homogeneity was divided into homogeneous and heterogeneous based on whether the contrast agent was evenly distributed in lesions. Wash-in and Wash-out refered to enhancement that appeared or disappeared earlier, at the same time, or later than the perinodular tissue. The morphology of nodules after perfusion can be divided into clear and unclear [12]. Ring enhancement was defined as an enhanced rim of peritumoral tissue that appears in the early phase and becomes more distinct in the late phase. Dynamic images of the whole process were stored for 3min, and all dynamic images of angiography were stored on the hard disk for offline analysis
Two ultrasound physicians (who have been engaged in thyroid angiography for more than 3 years) used QontraXt software to analyze all cases; both physicians were blinded to the pathological data. Briefly, the peak perfusion mode of each target nodule for analysis, was selected. First, the region of interest (ROI) along the maximum outer diameter of the nodule to obtain the time-intensity curve (TIC) inside the whole nodule was selected( Fig. 1), and then the peripheral annular ROI about 2–3 mm outward along the maximum outer diameter of the nodule was outlined to obtain the TIC at the outer edge of the nodule( Fig. 2). Each image was analyzed repeatedly three times, and the average value of the three times of data was taken, respectively. The angiographic parameters included: (1) peak (peak intensity) is the peak perfusion (%); (2) sharpness (Ascend slope) is the sharpness (1/s) of the gamma curve; (3) TP (time to peak); (4) AUC (area under the curve) is the area under the curve (1/s).
SPSS 21.0 statistical software was used for all the statistical analysis. K-S test was used to test whether the measurement data conformed to a normal distribution, and independent sample t-test and paired sample t-test were used for measurement data with normal distribution. A non-parametric test was adopted for measurement data with non-normal distribution. Meaningful indicators in the single-factor analysis were further included in logistic regression analysis. The receiver operating characteristic curve (ROC) was used to determine the diagnostic threshold. A P value < 0.05 was considered to be statistically significant.
A total of 175 malignant nodules, including 169 papillary carcinomas and 6 follicular carcinomas were identified. There were 115 benign nodules, including 107 nodular goiters and 8 thyroid adenomas. The length and diameter of benign nodules were 3.9 ~ 61.0 mm, with an average of 20.9 ± 13.13 mm. The length and diameter of malignant nodules were 3.1 ~ 40.2 mm, with an average of 11.6 ± 6.7 mm. Univariate analysis showed that the size, sex, and age of nodules were significantly different between benign and malignant groups (all p < 0.001). Most of the DTC's were male < 45 years old and with nodules ≤ 10mm (Table 1).
| parameter | Benign(115) | malignant(175) | p | X2 |
|---|---|---|---|---|
| Gender | 0.01 | 6.897 | ||
| Male | 17(14.8%) | 49(28%) | ||
| Female | 98(85.2%) | 126(72%) | ||
| Age | ＜0.001 | 17.859 | ||
| ＜45(y) | 31(27.0%) | 91(52.0%) | ||
| ≥ 45(y) | 84(73.0%) | 84(48.0%) | ||
| Nodule size | ＜0.001 | 45.588 | ||
| ≤ 10(mm) | 33(28.7%) | 121(69.1%) | ||
| ＞10(mm) | 82(71.3%) | 54(30.9%) | ||
| Enhancement degree | ＜0.001 | 55.126 | ||
| hyper-enhancement | 40(34.8%) | 19(10.9%) | ||
| Hypo-enhancement | 25(21.7%) | 116(66.3%) | ||
| Iso-enhancement | 50(43.5%) | 40(22.8%) | ||
| Enhancement homogeneity | ＜0.001 | 38.839 | ||
| Homogeneous | 71(61.7%) | 44(25.1%) | ||
| Heterogeneous | 44(38.3%) | 131(74.9%) | ||
| Ring enhancement | 0.033 | 4.916 | ||
| Absent | 97(84.3%) | 162(92.6%) | ||
| Present | 18(15.7%) | 13(7.4%) | ||
| Wash-in | ＜0.001 | 21.529 | ||
| Earlier | 35(30.4%) | 50(28.6%) | ||
| Later | 31(27.0%) | 94(53.7%) | ||
| Equal | 49(42.6%) | 31(17.7%) | ||
| Wash-out | ＜0.001 | 34.848 | ||
| Earlier | 23(20.0%) | 96(54.9%) | ||
| Later | 13(11.3%) | 21(12.0%) | ||
| Equal | 79(68.7%) | 58(33.1%) | ||
| Margin after angiography | ＜0.001 | 55.416 | ||
| Clear | 108(93.9%) | 92(52.6%) | ||
| Unclear | 7(6.1%) | 83(47.4%) |
Univariate analysis indicated that lower perfusion in malignant nodules (p < 0.001), uneven perfusion (p < 0.001), unclear margin after perfusion (p < 0.001), contrast agent entered later than benign nodules (p < 0.001), and subsided earlier than benign nodules (p < 0.001) (Table 1).
The parameters peak (p < 0.001) and TP at the outer edge of the thyroid cancer nodule were higher than those at the inner edge (p < 0.001), sharpness at the outer edge of the malignant nodule was lower than that at the inner edge (p < 0.001), and the peak at the outer edge of the benign nodule was lower than that at the inner edge (p = 0.047). Also, TP was lower than that at the inner edge (p = 0.017), sharpness (p < 0.001) and AUC at the outer edge of benign nodule were higher than those at the inner edge (p < 0.001), (Table 2).
| position | Benign (115) | malignant(175) | ||||||
|---|---|---|---|---|---|---|---|---|
| Peak(%) | TP(ms) | Sharpness(1/s) | AUC(1/s) | Peak(%) | TP(ms) | Sharpness(1/s) | AUC(1/s) | |
| Inside | 33.7 ± 8.2 | 45392 ± 18620 | 0.139 ± 0.056 | 4.0 ± 1.6 | 25.3 ± 10.8 | 43760 ± 16575 | 0.150 ± 0.082 | 3.9 ± 1.9 |
| Outside | 32.2 ± 9.1 | 42300 ± 14138 | 0.181 ± 0.050 | 4.7 ± 1.3 | 31.4 ± 9.9 | 48879 ± 18166 | 0.138 ± 0.060 | 4.1 ± 1.4 |
| t | 2.005 | 2.412 | -9.514 | 4.777 | -6.323 | -5.691 | 4.093 | -1.847 |
| p | 0.047 | 0.017 | ＜0.001 | ＜0.001 | ＜0.001 | ＜0.001 | ＜0.001 | 0.066 |
| Peak: peak intensity; TP: time to peak; Sharpness: ascend slope; AUC: area under the curve | ||||||||
Among benign and malignant nodules, the internal Peak of malignant nodules was significantly lower than that of benign nodules (p < 0.001), and the diagnostic threshold was 29.8. When ≤ 29.8 was taken as the malignant diagnostic criteria, its sensitivity, specificity, accuracy, and area under the curve were 70.4%, 80.6%, 76.6%, and 80.5%, respectively. TP at the outer edge of malignant nodules was significantly higher than benign nodules (p = 0.001), and its diagnostic threshold was 36,965. When > 36,965 was taken as the malignant diagnostic standard, its sensitivity, specificity, accuracy, and score below the curve were 77.1%, 41.7%, 63.1%, and 61.2%, respectively. Sharpness at the outer edge of the malignant nodule was significantly lower than that of the benign nodule (p < 0.001), and its diagnostic threshold was 0.159. When ≤ 0.159 was taken as the malignant diagnostic standard, its sensitivity, specificity, accuracy, and area under the curve were 73.0%, 74.3%, 73.8%, and 78.3%, respectively. The AUC at the outer edge of the malignant nodule was smaller than that of the benign nodule (p < 0.001), and its diagnostic threshold was 3.6. When < 3.6 was taken as the malignant diagnostic standard, its sensitivity, specificity, accuracy, and area under the curve were 84.3%, 38.9%, 56.9%, and 63.5%, respectively (Tables 3 and 4).
| Pathological type | Peak(%) | TP(ms) | Sharpness(1/s) | AUC(1/s) | ||||
|---|---|---|---|---|---|---|---|---|
| Outside | Inside | Outside | Inside | Outside | Inside | Outside | Inside | |
| Malignant(175) | 31.4 ± 9.9 | 25.3 ± 10.8 | 48879 ± 18166 | 43760 ± 16575 | 0.138 ± 0.060 | 0.150 ± 0.082 | 4.1 ± 1.4 | 3.9 ± 1.9 |
| Benign(115) | 32.2 ± 9.1 | 33.7 ± 8.2 | 42300 ± 14138 | 45392 ± 18620 | 0.181 ± 0.050 | 0.139 ± 0.056 | 4.7 ± 1.3 | 4.0 ± 1.6 |
| t | 0.701 | 7.146 | -3.285 | 0.781 | 6.431 | -1.343 | 3.682 | 0.555 |
| p | 0.484 | ＜0.001 | 0.001 | 0.436 | ＜0.001 | 0.180 | ＜0.001 | 0.579 |
| Peak: peak intensity; TP: time to peak; Sharpness: ascend slope; AUC: area under the curve | ||||||||
| Parameter | Area under curve(%) | p | Benign(115) | Malignant(175) | Sensitivity(%) | Specificity(%) | Accuracy(%) |
|---|---|---|---|---|---|---|---|
| Inside peak | 80.5 | ＜0.001 | 70.4 | 80.6 | 76.6 | ||
| ＞29.8 | 81(70.4%) | 34(19.4%) | |||||
| ≤29.8 | 34(29.6%) | 141(80.6%) | |||||
| Outside TP | 61.2 | 0.001 | 77.1 | 41.7 | 63.1 | ||
| ＞36965 | 67(58.3%) | 135(77.1%) | |||||
| ≤36965 | 48(41.7%) | 40(22.9%) | |||||
| Outside Sharpness | 78.3 | ＜0.001 | |||||
| ＞0.159 | 84(73.0%) 31(27.0%) | 45(25.7%) 130(74.3%) | 73.0 | 74.3 | 73.8 | ||
| ≤0.159 | |||||||
| Outside AUC | 63.5 | ＜0.001 | 84.3 | 38.9 | 56.9 | ||
| ≥ 3.6 | 97(84.3%) | 107(61.1%) | |||||
| ＜3.6 | 18(15.7%) | 68(38.9%) | |||||
| Peak: peak intensity; TP: time to peak; Sharpness: ascend slope; AUC: area under the curve | |||||||
Multivariate analysis showed that patients' age (p = 0.031), nodule size (p < 0.001), uneven perfusion (p < 0.001), low perfusion (p = 0.001), unclear margin after perfusion (p = 0.007), internal peak (p < 0.001), and sharpness (p < 0.001) were independent risk factors for diagnosing benign and malignant thyroid nodules (Table 5).
| Parameter | B | S.E, | Wals | p | Exp(B) | EXP(B) 的 95% C.I |
|---|---|---|---|---|---|---|
| Gender | 0.103 | 0.564 | 0.033 | 0.855 | 1.108 | 0.367 ~ 3.350 |
| Age | -1.036 | 0.481 | 4.629 | 0.031 | 0.355 | 0.138 ~ 0.912 |
| Nodule size | -3.214 | 0.810 | 15.734 | ＜0.001 | 0.040 | 0.008 ~ 0.197 |
| Ring enhancement | -0.426 | 0.759 | 0.315 | 0.574 | 0.653 | 0.147 ~ 2.892 |
| Margin after angiography | 1.706 | 0.636 | 7.192 | 0.007 | 5.508 | 1.583 ~ 19.166 |
| Enhancement homogeneity | 3.672 | 0.820 | 20.072 | ＜0.001 | 39.327 | 7.889 ~ 196.034 |
| Enhancement degree | 1.676 | 0.516 | 10.543 | 0.001 | 5.342 | 1.943 ~ 14.686 |
| Wash-in | 0.517 | 0.557 | 0.861 | 0.354 | 1.677 | 0.563 ~ 4.998 |
| Wash-out | 1.513 | 0.781 | 3.754 | 0.053 | 4.540 | 0.983 ~ 20.976 |
| Inside peak | 2.179 | 0.499 | 19.102 | ＜0.001 | 8.835 | 3.326 ~ 23.472 |
| Outside TP | 0.570 | 0.527 | 1.171 | 0.279 | 1.768 | 0.630 ~ 4.966 |
| Outside Sharpness | 2.230 | 0.509 | 19.175 | ＜0.001 | 9.298 | 3.427 ~ 25.225 |
| Outside AUC | 0.356 | 0.575 | 0.383 | 0.536 | 1.428 | 0.463 ~ 4.406 |
| Constant | -3.330 | 1.017 | 10.718 | 0.001 | 0.036 | |
| Peak: peak intensity; TP: time to peak; Sharpness: ascend slope; AUC: area under the curve | ||||||
According to the EFSUMB guidelines, CEUS is a promising non-invasive method for differentiating benign and malignant thyroid nodules. The type and severity of tumors can be determined by analyzing the distribution characteristics, enhancement degree, and time intensity curve (TIC) of contrast agents in the lesions. However, the data of CEUS qualitative and quantitative evaluation parameters overlap with the data of benign and malignant nodule standards; thus, the interpretation of tumor micro-vessels may be challenging. Therefore, when evaluating thyroid nodules, clinical data, conventional ultrasound, and other imaging findings should be combined for interpretation to improve diagnostic accuracy [13].
Tumor blood vessels are heterogeneous. There are differences between tumor blood vessels and non-tumor blood vessels. Also, benign and malignant tumors with different pathological classifications, pathological proceses, and regions of the same type of tumor may have different blood vessels [14]. Because of the high interstitial pressure in the tumor, more blood vessels are compressed and collapsed, so the blood supply in the tumor is reduced [15]. Therefore, some scholars have focused their attention on the area around the tumor. Relevant literature reports on the area around breast and liver tumors have provided new characteristic auxiliary information for clinical use, which can help surgeons make more correct surgical decisions. This study examined the interior of thyroid nodules and the peripheral ultrasound contrast parameter information of thyroid nodules in order to improve the diagnostic accuracy of ultrasound contrast and benefit patients.
Some studies [8, 16–19] suggested that hypo enhancement is closely related to malignant tumors, which is consistent with our data. In this study, the proportion of hypo enhancement in malignant nodules (66.3%) was significantly higher than in benign nodules (21.7%), which may be due to the following aspects: first, because the proportion of cancer nodules ≤ 10mm in this study was large (69.1%), small tumors did not form a large number of mature tumor vascular beds, and the blood supply was insufficient, and in turn, no obvious perfusion was seen [18, 20, 21]. Secondly, papillary thyroid carcinoma often shows dense interstitial fibrosis [22]. The increase of blood vessels is usually related to cell proliferation in the tumor state, and fibrosis reduces the vascular density in the nodules [22, 23]. Therefore, nodule CEUS is more likely to present hypo enhancement.
According to the Guidelines for the Diagnosis and Treatment of Adult Thyroid Nodules and Differentiated Thyroid Cancer issued by the American Thyroid Association (ATA) in 2015 and the Chinese Guidelines for the Ultrasonic Malignancy Risk Stratification of Thyroid Nodules (C-TIRADS) issued by China in 2020, irregular or unclear edges in conventional ultrasound are important indicators for the diagnosis of malignant nodules [24, 25]. Yi et al. [12] found that unclear margins after contrast enhancement are an independent risk factor for malignant thyroid tumors. Consistent with this study, the proportion of unclear margins after contrast ultrasound in DTC (47.4%) was also significantly higher than that of benign nodules (6.1%). The analysis of the causes may be related to the invasiveness of the tumor. CEUS focuses on the analysis of the microvascular pattern. The characteristics of the tumor lead to the tumor invading outwards, while the peripheral area of the lesion is relatively dense, and the tumor is easy to invade outwards, so it will appear unclear in CEUS [20].
Some scholars [26–28] found that uneven enhancement is more common in malignant thyroid tumors. Moreover, Zhang et al. [27] found that ring enhancement was predictive of benign lesions, whereas heterogeneous enhancement was helpful for detecting malignant lesions, also, the CEUS enhancement has a diagnostic sensitivity specificity and accuracy of 88.2%, 92.5%, and 90.4%, respectively. Consistent with the results of this study, 131 of 175 malignant nodules showed uneven enhancement (74.9%), which may be due to neovascularization. Generally speaking, the neovascularization of malignant lesions is divided into peripheral and central areas, and their vascular distribution is different. The blood vessels in the central area are relatively sparse, which is prone to incomplete or complete necrosis. The distribution of new blood vessels in the whole lesion is uneven and complex, which may lead to uneven enhancement [20].
This study found no significant difference in the AUC of malignant thyroid nodules. Yet, other quantitative parameters of the inner and outer edges of the thyroid gland showed statistical significance, which to some extent, indicated a difference between the inner and outer edges of the thyroid. Further refining of the benign and malignant nodules revealed that the peak in the malignant nodules was significantly lower than that in the benign nodules, and there were significant differences between single and multiple factors. It is possible that the differentiation of new blood supply in the malignant nodules was poor, the distribution was uneven, or the micro-vessels were not completely established, so distribution was disordered, dense, and distorted, as well as the calcification, necrosis or fibrosis in the nodules caused the internal perfusion intensity to be lower than the outer edge. Therefore, when this manifestation occurs, it is necessary to consider the possibility of malignancy. Recent studies [29] found that the proportion (46.15%) of malignant nodules R-AS > 1 (the ratio of nodule's ascending slope to surrounding normal thyroid tissue's ascending slope) was significantly higher than that of benign nodules (12.86%) (p < 0.001), indicating that the ascending slope of malignant nodules was significantly higher than that of benign nodules, which is not consistent with our results. Although the mean value of sharpness in malignant nodules is higher than in benign nodules, the difference is insignificant (p = 0.180). On the contrary, sharpness at the outer edge of malignant nodules was significantly lower than that in benign nodules (p < 0.001), which indicated that the perfusion speed at the outer edge of malignant nodules was slow. The analysis may be that most benign nodules are parenchyma thyroid tissue divided into nodules by fibrous tissue due to the infiltration of many lymphocytes. There was no significant difference between the peripheral thyroid tissue and the peripheral thyroid tissue in histopathology, suggesting that the peripheral blood flow perfusion speed was no different from the peripheral thyroid tissue. The biological behavior of malignant nodules was characterized by invasive growth, destruction of surrounding tissues, destruction of normal blood supply, obstruction, or even interruption of blood flow from the outer edge [20]. Jiang et al. [30] quantitatively analyzed CEUS on thyroid nodules and found that papillary thyroid carcinoma showed slow enhancement.
Lei et al. [31] found a difference in age benign and malignant thyroid nodules, which was consistent with our data. Hughes et al. [32] considered that the most common PTC tumor is PTMC over 45 years old, which was different from our findings. In our study, patients younger than 45 accounted for more than 52.0% of DTC cases and only 27.0% of benign cases. These differences among studies may be explained as follows: first, different pathological types were explored. The former mainly studied a PTC in DTC, while the latter mainly investigated the DTC. Second, the younger DTC was reported by some scholars [33]. Under the same environment, the risk of thyroid nodules increases significantly with the decrease in exposure age. Third, with the diversification of detection methods, the high sensitivity of detection instruments, and the improvement of people's health awareness, the detection rate increases significantly, making some thyroid nodules appear earlier [34, 35].
In this study, it was also found that the proportion of malignant nodules (69.1%) ≤ 10mm was significantly higher than that of benign nodules (28.7%), which was consistent with the research of Zheng and other scholars [36].
The present study has some limitations. First, this was a retrospective, single-center study with a relatively small sample size. Second, the operating physician's ROI profile in the process of angiographic analysis was not completely consistent. Finally, although the average value was taken, the deviation still existed, so a more scientific method should be tested in the future.
The qualitative and quantitative analysis of CEUS has a certain value in the differential diagnosis of benign and malignant differentiated thyroid cancer and can provide a certain basis for clinical diagnosis.
Acknowledgments
Not applicable.
Author contributions
#Author Jinfang Fan and Author Lingling Tao contributed equally to this work.
Study concept and design: Jinfang Fan, Wei Zhou, Lingling Tao. Data acquisition: Jinfang Fan, Weiwei Zhan, Lingling Tao. Technical and material support: Jinfang Fan, Weiwei Li, Lingling Tao. Data analysis: Jinfang Fan, Lijun Kuang, Lingling Tao. Drafting and revision of the manuscript: Jinfang Fan ,Yingyan Zhao, Lingling Tao . All authors read and approved the final manuscript.
Funding
None.
Ethics approval and consent to participate
This retrospective study was approved by the Ethics Committee of the Ruijin Hospital, LuWan Branch, Shanghai Jiao Tong University School of Medicine. The procedures of reviewing the research were in line with the ethical standards of the institutional and national research committees.
Consent for publication
All participants signed a written informed consent document.
Competing interests
The authors declare that they have no competing interests.
Availability of data and materials
The datasets used and analyzed during the current study available from the corresponding author on reasonable request.
Author details
1 Department of ultrasound, RuiJin Hospital/LuWan Branch, School of Medicine, Shanghai Jiaotong University, No. 149, Chongqing South Road, Huangpu District , Shanghai,200020, China.
2Department of Ultrasound, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, No. 197, ruijin 2 road, Shanghai Huangpu district, Shanghai, 200025, China.