Beyond single cut-off values in ultrasound: limitations and implications for context aware radiology reporting
October 28, 2026Contrast-enhanced US with Perfluorobutane to Diagnose Small Lateral Cervical Lymph Node Metastases of Papillary Thyroid Carcinoma
| Objectives |
Although metastasis of lateral cervical lymph nodes (LNs) is common in papillary thyroid carcinoma (PTC), correctly diagnosing small metastatic LNs with US remains challenging. The use of contrast-enhanced US (CEUS), especially the postvascular phase of CEUS with perfluorobutane contrast material, might contribute to improved diagnosis of metastatic LNs in PTC. The purpose of this study is to assess the diagnostic value of the postvascular phase of CEUS with perfluorobutane in suspicious small lateral cervical LNs (short-axis diameter ≤8 mm) in patients with PTC. |
| Authors |
Xiao L, Zhou J, Tan W, Liu Y, Zheng H, Wang G, Zheng W, Pei X, Yang A, Liu L. Departments of Ultrasound and Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China; and Department of Ultrasound, Sun Yat-sen University, Affiliated Hospital 8, Shenzhen, China. |
| Journal |
Radiology. 2023;307:e221465. doi: 10.1148/radiol.221465 |
| Methods |
Single-center study prospectively enrolled consecutive participants with confirmed PTC and suspicious LNs at US from October 2020 to October 2021. All participants underwent CEUS, 1 week before biopsy or surgery, with intravenous perfluorobutane contrast material to visualize the LNs in the vascular phase (5–60 seconds after injection) and postvascular phase (10–30 minutes after injection). The reference standard was cytologic and surgical histologic assessment of the LNs. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of sonographic features were calculated, and the diagnostic performance of US, CEUS, and the combination of postvascular phase and US features was assessed using multivariable logistic regression models. |
| Results |
A total of 135 participants (median age, 36 years [IQR, 30–46 years]; 100 women) with 161 suspicious LNs at US were evaluated, including 67 metastatic and 94 benign LNs. The specificity of perfusion defect as a sonographic feature in the vascular phase reached 96% (90 of 94 LNs), and the negative predictive value of non-isoenhancement (ie, hypoenhancement, partial enhancement, and no enhancement) in the postvascular phase reached 100% (83 of 83 LNs). The area under the receiver operating characteristic curve (AUC) of the combination of postvascular phase and US features was 0.94 (95% CI: 0.89, 0.97), significantly higher than that of US features alone (AUC, 0.73; 95% CI: 0.65, 0.79; P < .001). |
| Conclusions |
The postvascular phase of CEUS with perfluorobutane demonstrated excellent performance in diagnosing suspicious small lateral LNs in participants with PTC. Isoenhancing small lateral LNs in the postvascular phase of CEUS were unlikely to be malignant, which may avert the need for biopsy. Larger multicenter data are needed to confirm the diagnostic performance of CEUS with perfluorobutane for metastatic LNs. |
| Key points |
Perfusion defect in the vascular phase of contrast-enhanced US with perfluorobutane demonstrated high specificity (96%), and non-isoenhancement in the postvascular phase demonstrated high accuracy (93%) and negative predictive value (100%). The combination of US and postvascular phase features performed better than US features alone (area under the receiver operating characteristic curve, 0.94 vs 0.73; P < .001) for diagnosis of suspicious small lateral cervical LNs. |
| Link (DOI) | https://pubs.rsna.org/doi/10.1148/radiol.221465 |
| Ultrasound speciality |
Carcinoma, Papillary, Contrast Media, Lymph Nodes, Lymphatic Metastasis, Ultrasonography |
Short-Review by:
Prof. Dr. Jose Luis del Cura
Department of Radiology
Donostia University Hospital
Spain
Strengths:
Consecutive patients
New US contrast agent. This contrast agent acts differently from sulfur hexafluoride: it has the property of being phagocytosed by macrophages.
in the postvascular phase, all lymph nodes showing isoenhancement (83 of 83) were benign and all metastatic nodes (67 of 67) were non-isoenhancing (partially enhancing, hypoenhancing, or nonenhancing).
Weaknesses:
Small series. Single-centre study. Young age of the patients (mean 36 years).
Many patients (44%) have Hashimoto disease. Performed in Asian patients (results can be different in a different population).
Long time (10–30 minutes) needed to observe contrast enhancement with perfluorobutane postvascular phase.
Personally thinking:
Recently a new US contrast agent has been developed: perfublutane. This contrast agent has the property of being phagocytosed by macrophages. So, after an initial vascular phase a postvascular phase is followed. The usefulness of this new molecule is just being tested in several territories, and the thyroid is one of them.
From a clinical point of view, the most interesting finding is that, in the postvascular phase, all lymph nodes showing isoenhancement were benign and all metastatic nodes were non-isoenhancing” This means that it can be an excellent technique to confidently discard malignancy when all the LN demonstrates isohenhancement, making the biopsy unnecessary. It may help avoid an invasive biopsy procedure in more than 50% of nodes (in this study, 83 161 lymph nodes).
Also, the combination of noncontrast US and postvascular phase features had a markedly improved diagnostic performance compared with noncontrast US features only.
The diagnostic performance of postvascular perfublutane CEUS is remarkable considering that only indeterminate or suspicious for malignancy lateral cervical lymph nodes less than or equal to 8 mm in short-axis diameter were included.
The main question to be addressed, however, is if including a new costly an long exploration instead performing an easy-to-perform FNA is justified by the benefits.
