Multicenter Retrospective Study of Dual-mode Contrast-enhanced Ultrasound Predictive Model for Lymph Node Metastasis Burden in T1N0M0 Papillary Thyroid Carcinoma

Papillary thyroid carcinoma (PTC) is the most prevalent subtype of thyroid malignancy, accounting for approximately 80%-90% of all thyroid cancers globally. With the widespread application of high-resolution ultrasound in routine physical examinations, an increasing number of early-stage PTC cases, particularly those classified as T1N0M0 (tumor size ≤2 cm, no clinical evidence of lymph node metastasis, and no distant metastasis), are being detected. Despite the relatively favorable prognosis of T1N0M0 PTC, the presence and burden of central lymph node metastasis (CLNM) remain critical factors that directly guide individualized treatment strategies and long-term follow-up plans for patients.

Similarly, the burden of CLNM exerts a pivotal impact on the individualized management of T1N0M0 PTC patients, as distinct metastasis burdens correspond to significantly different therapeutic approaches. Specifically, lymph node metastasis of any burden serves as an absolute contraindication to thermal ablation, a minimally invasive treatment option increasingly used for low-risk PTC; patients with low-burden CLNM (defined as ≤3 positive central lymph nodes with no extracapsular extension) are typically suitable for thyroid lobectomy combined with central lymph node dissection, which balances tumor control and preservation of thyroid function; in contrast, high-burden CLNM (defined as >3 positive central lymph nodes or presence of extracapsular extension) recommends total thyroidectomy with comprehensive central lymph node dissection, followed by radioactive iodine therapy when necessary to reduce the risk of recurrence. However, conventional preoperative imaging examinations, including conventional ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), have inherent limitations in diagnosing CLNM and evaluating its burden. Conventional ultrasound relies primarily on morphological features (e.g., lymph node size, shape, cortical thickness) which lack sufficient specificity, while CT and MRI are associated with radiation exposure (for CT) or high cost (for MRI) and still demonstrate low sensitivity and specificity for detecting small or micrometastatic lymph nodes in the central compartment, leading to frequent misdiagnosis or underdiagnosis.

This limitation poses a clinical dilemma: inaccurate preoperative assessment of CLNM burden may result in overtreatment (e.g., unnecessary total thyroidectomy in patients with no or low-burden metastasis, leading to lifelong thyroid hormone replacement therapy) or undertreatment (e.g., lobectomy in patients with high-burden metastasis, increasing the risk of local recurrence and the need for reoperation). Therefore, there is an urgent clinical need for a non-invasive, accurate, and cost-effective imaging method to preoperatively evaluate the burden of CLNM in T1N0M0 PTC patients.

Dynamic contrast-enhanced ultrasound (CEUS) has emerged as a promising imaging technique in the field of thyroid and lymph node diagnostics. By intravenously injecting a microbubble contrast agent, CEUS can dynamically visualize the microvascular perfusion of target tissues in real time, providing qualitative (e.g., enhancement pattern, homogeneity, presence of perfusion defects) and quantitative (e.g., time to peak, peak intensity, wash-in rate, wash-out rate) parameters that reflect the pathological microenvironment of lesions. Compared with conventional imaging modalities, CEUS offers several advantages, including non-radiation exposure, real-time imaging, high spatial and temporal resolution, and the ability to assess microcirculation, which may enable more accurate identification of metastatic lymph nodes and evaluation of their burden.

To address the aforementioned clinical gap, this multicenter retrospective cross-sectional study was designed to explore the value of CEUS in preoperatively predicting the burden of CLNM in T1N0M0 PTC patients. The study enrolled 600 consecutive patients with T1N0M0 PTC who were admitted to three tertiary hospitals (the lead center and two collaborating centers) from June 2018 to June 2025 and confirmed by postoperative pathology. All patients met strict inclusion criteria: (1) histopathologically confirmed PTC after surgery; (2) preoperative tumor staging consistent with T1N0M0 based on clinical examination and conventional imaging; (3) no history of thyroid surgery, radioactive iodine therapy, or other malignant tumors; (4) availability of complete preoperative CEUS data of the thyroid and central compartment lymph nodes; and (5) no contraindications to contrast agent injection. Patients with incomplete clinical, imaging, or pathological data were excluded from the study.