Thyroid nodules are commonly encountered lesions and have been observed in 50% of autopsied patients (1). The estimated annual incidence rate of 0.1% in the US suggests 300,000 newly diagnosed nodules as of 2005 (2). Although only 1 of 20 clinically identified nodules is malignant (3), it is important to exclude the presence of a malignant thyroid lesion (2,4).

Previous studies have demonstrated the feasibility of contrast-enhanced ultrasound (CEUS) for the differentiation of benign and malignant thyroid nodules (5). Nemec et al (6) reported that the complete CEUS data of 42 patients (73.8% benign and 26.2% malignant nodules) revealed a significant difference in enhancement between benign and malignant nodules. Furthermore, CEUS demonstrated a sensitivity of 76.9%, specificity of 84.8% and accuracy of 82.6%. Quantitative analysis of CEUS using a microbubble contrast agent allows the differentiation of benign and malignant thyroid nodules and may potentially serve, in addition to grey-scale and Doppler ultrasound, as an adjunctive tool in the assessment of patients with thyroid nodules. Hornung et al (7) reported that CEUS represents a highly sensitive method for the detection of the microvascularization of thyroid carcinomas. Future studies should compare these findings to benign pathologies in order to establish CEUS as a standard diagnostic procedure in the preoperative evaluation of suspicious thyroid nodules. Zhang et al (8) reported that CEUS enhancement patterns were different in benign and malignant lesions. Ring enhancement was predictive of benign lesions, whereas heterogeneous enhancement was helpful for detecting malignant lesions.

The ultrasonic imaging characteristics of 68 patients with thyroid carcinoma proved by pathology were retrospectively analyzed in the present study. The correlation of real-time CEUS characteristic was mainly discussed in association with the lesion size.

A tumor is a type of typical vascular-dependent lesion. Small blood vessels with diameters <40 µm can be detected by CEUS. Previously, clear results have been achieved in studying tumor vascular perfusion features by CEUS for focal liver lesions, but the study of its application in thyroid nodules was only preliminary (9–12). In the present study, real-time CEUS images for 68 cases of patients with thyroid cancer were retrospectively analyzed with the main purpose of exploring the association between characteristics of thyroid carcinomas in real-time CEUS and tumor sizes.

In the present study, the absolute enhancement beginning time for different lesions were not statistically significant, as the enhancement beginning time following injection of the contrast agent could be affected by various factors, such as differences in time of contrast agent bolus injection among different operators and difference in intimate circulation of the contrast agent among different individuals. Therefore, relative enhancement beginning time was used to evaluate the enhancement time of different lesions. The majority of lesions enhanced later than the surrounding thyroid gland and the differences in features of enhancement for lesions among different groups were not statistically significant. The predominant enhancement pattern in different groups was heterogeneous concentric enhancement, and the majority of lesions showed less clear or poorly defined margins following enhancement. The study by Zheng et al (13) reported that 35 thyroid carcinomas presented three enhancement patterns with CEUS. These were type I: 23 lesions enhanced in a pattern of ring with centripetal fill-in, however, the central part had no contrast agent filling; type II: 5 lesions enhanced regularly and homogeneously; and type III: 7 lesions enhanced irregularly and homogeneously.

We believe that the above enhancement features are in accordance with the pathological features. Vascular pathological anatomy for thyroid cancer is complicated. Generally, neovascular could be divided into surrounding and central area, which showed different vascular distribution characteristics. Blood vessels in the surrounding area are relatively concentrated and the tumor usually grows infiltratively outward, which leads to the formation of less clear or poorly defined margins following enhancement; while blood vessels in the central area are relatively less concentrated. Therefore, the difference in the abundance of blood vessels between the surrounding and central area are the main reason for concentric enhancement. For the growth heterogeneity and neovascular damage caused by malignant infiltration, thyroid cancer is always combined with fibrosis and hyalinization degeneration. The original vascular networks would be damaged, which results in coexistence of abundant blood supply in certain areas and inabundant blood supply in other areas. Existence of various arteriovenous fistulas enhanced the imbalance of vascular networks (14). All the abovementioned reasons contribute to the heterogeneous enhancement in CEUS for thyroid cancer.

As indicated in the present study, the incidence of perfusion defect within lesions increased with the increase of lesion diameter, which is consistent with the growth feature of malignant tumor. A previous study reported that during the growth of the malignant tumor, the doubling time for vascular endothelial cells and tumor cells is different, which indicates that the tumor growth speed is much higher than the formation speed of microvessels (15). The increase of the microvessel number is relatively slower and the incidence is more evident with the growth of the tumor. With the growth of the tumor, the blood supply in the lesion is poorer, so the incidence of part or complete defect is higher, and this results in a higher rate of local perfusion defects.

Bartolotta et al (5) identified that the enhancement pattern of thyroid nodules in CEUS was closely associated with nodule size, which was indicated as an inabundant blood supply in CEUS for malignant lesions <10 mm, few nodular enhancements for 10–20 mm lesion and diffuse enhancement for lesions >20 mm. With a larger sample, the enhancement features in CEUS for groups with different lesion sizes were analyzed in this study. The results indicate that, in groups with a lesion diameter <10 mm and between 10–20 mm, CEUS mainly showed a not significant enhancement, but mainly hyper-enhancement in the group with a lesion size >20 mm. The following may be the reasons for this: Growth of the tumor consists of two stages, from the slow-growing stage without blood vessels (pre-vascular phase) to fast-growing stage with blood vessels (vascular phase). Without or with fewer blood vessels, the enhancement observed in CEUS for relatively smaller tumors was mainly insignificant enhancement. When the tumor grows quickly, various new blood vessels form under the introduction of multiple angiogenic factors to meet the requirements of fast growth. With complicated vascular network, hyper-enhancement was usually observed in relatively large thyroid cancer lesions.

In conclusion, there is a certain correlation between enhancement features in CEUS for thyroid cancer and lesion size. In lesions with diameters <10 mm or between 10–20 mm, insignificant enhancement was usually observed, while in lesions with diameters >20 mm, hyper-enhancement was usually observed. The incidence of perfusion defects within the lesion increases with larger lesion diameters. Real-time CEUS can provide valuable information for clinical diagnosis.