Contrast-Enhanced Ultrasound in the Differential Diagnosis and Risk Stratification of ACR TI-RADS Category 4 and 5 Thyroid Nodules With Non-Hypovascular

OBJECTIVE: This study aims to investigate the value of contrast-enhanced ultrasound (CEUS) in the differential diagnosis and risk stratification of ACR TI-RADS category 4 and 5 thyroid nodules with non-hypovascular. METHODS: From January 2016 to December 2019 in our hospital, 217 ACR TI-RADS category 4 and 5 nodules with non-hypovascular in 210 consecutive patients were included for a derivation cohort. With surgery and/or fine-needle aspiration (FNA) as a reference, conventional ultrasound (US) features and CEUS features were analyzed. Multivariate logistic regression analysis was used to screen the independent risk factors and establish a risk predictive model. Between January 2020 and March 2021, a second cohort of 100 consecutive patients with 101 nodules were included for an external validation cohort. The model was converted into a simplified risk score and was validated in the validation cohort. The area under the receiver operating characteristic curves (AUC) were used to assess the models’ diagnostic performance. RESULTS: Micro-calcification, irregular margin, earlier wash-out, centripetal enhancement, and absence of ring enhancement were independent risk factors and strongly discriminated malignancy in the derivation cohort (AUC = 0.921, 95% CI 0.876–0.953) and the validation cohort (0.900, 0.824–0.951). There was no significant difference (P = 0.3282) between the conventional US and CEUS in differentiating malignant non-hypovascular thyroid nodules, but a combination of them (the predictive model) had better performance than the single method (all P <0.05), with a sensitivity of 87.0%, specificity of 86.2%, and accuracy of 86.6% in the derivation cohort. The risk score based on the independent risk factors divided non-hypovascular thyroid nodules into low-suspicious (0–3 points; malignancy risk <50%) and high-suspicious (4–7 points; malignancy risk ≥ 50%), the latter with nodule ≥10mm was recommended for FNA. The risk score showed a good ability of risk stratification in the validation cohort. Comparing ACR TI-RADS in screening suitable non-hypovascular nodules for FNA, the risk score could avoid 30.8% benign nodules for FNA. CONCLUSIONS: CEUS is helpful in combination with conventional US in differentiating ACR TI-RADS category 4 and 5 nodules with non-hypovascular. The risk score in this study has the potential to improve the diagnosis and risk stratification of non-hypovascular thyroid nodules.