DWI has a good diagnostic value for thyroid disease. Previous studies [17, 19] showed that ADC values of the thyroid gland can be used to assess the activity of Graves’ disease and to differentiate Graves’ disease from painless thyroiditis in patients with untreated thyrotoxicosis. The ADC value is a noninvasive imaging approach used for differentiating malignant from benign solitary thyroid nodules, but the published protocols suffer from flaws and previous studies focus on the ADC [11, 12, 14,15,16, 18]. Therefore, the aim of the present study was to investigate the diagnostic performance of multiple MRI parameters in differentiating malignant from benign thyroid nodules. The results showed that ADC, irregular shape, ring sign, and cystic degeneration were independently associated with malignant thyroid nodules. While the irregular shape, ring sign, and cystic degeneration can be subjective and dependent upon the radiologist’s experience, ADC can provide quantitative information to differentiate thyroid carcinoma from benign thyroid nodules. The present study suggests that combining subjective MRI features to a quantitative measurement could improve the diagnostic yield of MRI for malignant thyroid nodules.
The incidence of thyroid cancer is rapidly increasing, with a 3% estimated annual increase in the United States [20]. Similar patterns have been reported in Canada, Australia, China, and Western Europe [20, 21]. US is the primary imaging modality to assess thyroid nodules [22]. FNAB is an accurate and cost-effective method for evaluating thyroid nodules, with high diagnostic sensitivity and specificity [23]. Nevertheless, US-guided FNAB is an invasive procedure and cannot distinguish between benign and malignant non-papillary follicular and oxyphilic cell lesions [6, 12]. MRI is an effective noninvasive modality to differentiate malignant from benign tumors [24]. A number of MRI studies examined the ADC values of thyroid nodules [8, 22, 25], but image quality was considered to be relatively poor because of susceptibility artifacts, motion artifacts, and low signal-to-noise ratio with previous head and neck joint coil. One previous study showed that only 26/40 patients had images that could be interpreted because of distortion [8]. Another study showed that patient motion was the major factor of exclusion due to breathing, swallowing, and coughing [2]. In addition, the b value is a critical factor affecting image quality and ADC values. When low b value is used, the ADC value tends to be higher due to the contribution of perfusion. Applying high maximum b values may be preferable when ADC measurements are performed to differentiate malignant from benign tissues, exclusively based on their water diffusion characteristics. Nevertheless, the signal-to-noise ratio decreases as the b value increases, thus limiting the maximum b value. In addition, we used a neck surface coil to increase the signal-to-noise ratio. Indeed, because the coil was close to the surface of neck, it could minimize the air-tissue boundary for reducing susceptibility artifacts. Therefore, a relatively high b value (800 × 10− 3 s/mm2) was used, which could better reflect the actual diffusion characteristics in this study. In addition, we used special techniques to improve image quality. A relatively small FOV (14 × 14 cm) was used to reduce susceptibility artifacts. Shim blocks were used to optimize magnetic homogeneity in the thyroid region. All patients received respiratory training to improve movement-related problems. We used a breath-hold technique on dynamic contrast-enhanced MRI phase to reduce breathing motion artifacts and added saturated zone to reduce carotid artery pulsatile artifacts. Therefore, 239 of the 254 patients showed excellent image quality in this study.
Some studies have shown that DWI can differentiate benign from malignant thyroid nodules [7, 12, 14, 26]. Nevertheless, the numbers of cases included in these studies were relatively small and the findings were sometimes inconclusive [16, 26]. The sample size of the present study was relatively large, with 181 patients and 259 thyroid lesions. Malignant nodules in this study showed lower ADC values compared with benign nodules. Logistic regression showed that ADC values had a high prediction value for the malignant status of thyroid lesions. Cytological features of malignant thyroid nodules in this study included enlarged and irregular nuclei, increased cell density, and relatively severe desmoplastic response, whereas abundant follicles, extracellular fluid and smaller cell density resulted in higher ADC values in adenoma and nodular goiter. These results were consistent with previous studies [18, 26].
Dynamic contrast enhancement can play a complementary role in the diagnosis of thyroid carcinoma. During the delayed phase, the ring sign (with a central washout enhancement) was seen in a large number of malignant thyroid nodules, which was not reported in previous studies. The central tumor area with washout indicates active growth of tumor cells, whereas the peripheral area is mainly composed of loose connective tissue with abundant intercellular matrix. Peripherally enhanced areas in malignant thyroid tumors during the delayed phase may also be related to the fibrous stroma of the tumor and the presence of vascular fibrotic stroma. Malignant thyroid nodules in the present study showed irregular shape after contrast agent. The histopathological characteristics of thyroid carcinoma indicate the invasive and heterogeneous growing pattern. One recently published study [27] also showed that irregular margins on US were strong predictor of malignancy.
In the present study, cystic degeneration, high signal cystic area on T1WI, and the pseudocapsule sign were significantly more frequent in benign thyroid nodules than in malignant nodules. Nodular goiter was the main pathological type of benign thyroid nodules in this study. Due to the relative abundance of colloid follicles and hemorrhage, nodular goiter showed cystic changes and high signal intensity in cystic areas. Shi et al. [26] showed similar results. Na et al. [28] showed that the risk of malignancy of partially cystic nodules was lower than the risk of malignancy of purely solid nodules. Similar to previous studies [28], the present study showed that 68.9% of thyroid benign nodules showed cystic changes, but only 17.1% of the malignant lesions showed cystic changes. The pseudocapsule sign was not the real capsule of tumor, but showed a clear capsule after contrast agent administration because the tumor compressed the peripheral thyroid parenchyma and caused fibrosis. Therefore, the pseudocapsule sign indicates a chronic and benign pathological process.
In this study, the enhancement degree between the two groups was significantly different, but there was major overlap between the two groups. Nodular goiter and adenoma showed moderate or marked enhancement with abundant hyperplasia of thyroid follicles. Follicular thyroid carcinoma showed marked enhancement because of abundant hyperplasia of thyroid follicles and neovascularity. Papillary thyroid carcinomas demonstrated moderate or marked enhancement with increased cell density, severe desmoplastic response, and cell proliferation, which were consistent with previous studies [26, 29].
Taken together, the present study strongly suggests that multiple MRI parameters should be considered when evaluating thyroid nodules. While irregular shape, ring sign, and cystic degeneration can be subjective and dependent upon the radiologist’s experience, ADC can provide quantitative information to differentiate thyroid carcinoma from benign thyroid nodules. On the other hand, whether the parameters observed in the present study are better than other modalities such as US, computed tomography, and scintigraphy [30] require additional studies.
This study has several limitations. Firstly, this study was retrospective in design, leading to selection bias and therefore undermining the validity of the results. Prospective studies with larger sample size would increase the credibility of the results. Secondly, thyroid nodules measuring < 3 mm were not included. Improvements in MRI software and using smaller slice gaps may facilitate the detection of smaller lesions in future studies. Importantly, it has been shown that small thyroid lesions are at higher risk of malignancy than larger ones [21]. Therefore, the present study probably underreported the number of malignant lesions. Thirdly, in this study, the major malignant pathological type was papillary carcinoma, while the major benign type was nodular goiter, similar to previous studies [18, 26]. Nevertheless, the underrepresentation of rarer pathological types could bias the results. We need to enlarge the samples in the following studies. Fourthly, our center only has a 1.5-T MRI scanner and differences in imaging parameters for malignant thyroid nodules could not be compared with a 3-T scanner. In addition, 1.5 T MRI scanners cannot implement multiple b values and we applied a high b value to better reflect the value of diffusion. Meanwhile, with technological and software development, some advanced diffusion imaging like diffusion tensor imaging has been used for the differentiation between malignant and benign tumors of the head and neck [31]. Our center could not implement those different advanced diffusion imaging modules. Furthermore, we could not determine the K-trans value because dynamic contrast enhancement at our center is routinely done at 30 s, 60 s, and then every minute, and only the trend of dynamic enhancement could be extracted. Fifthly, we used a neck surface coil to increase signal noise ratio and many techniques to reduce artifacts, but we did not compare the differences among the coils and techniques. In addition, we did not compare the difference among different pathological types. Finally, the irregular shape, ring sign, and cystic degeneration are indeed subjective, but these parameters had nevertheless high sensitivity and specificity. These parameters have not been reported before, and could have some value for the management of patients with thyroid nodule.