Radiofrequency and Microwave Ablation as Minimally Invasive Approaches for Managing Benign Thyroid Nodule

Summary

This protocol describes radiofrequency ablation and microwave ablation. Both these techniques can significantly reduce the volume of thyroid nodules while preserving normal thyroid function and minimizing complications, making them the preferred minimally invasive treatments for benign thyroid nodules.

Abstract

The management of benign thyroid nodules has evolved significantly with the advent of minimally invasive techniques, offering patients effective alternatives to traditional surgery. Among these, radiofrequency ablation (RFA) and microwave ablation (MWA) have emerged as the leading modalities. RFA, the most widely adopted method, uses high frequency alternating current to induce thermal coagulation. MWA, though less established in thyroid applications, employs electromagnetic waves to generate rapid and intense heat, making it particularly effective for larger or hypervascular nodules. These approaches are particularly advantageous for patients with symptomatic nodules or cosmetic concerns, as they preserve thyroid function while minimizing complications and recovery time. This protocol establishes a standardized approach for RFA and MWA of benign thyroid nodules. The procedure begins with cytological confirmation (Bethesda II) and ultrasound evaluation, followed by local anesthesia and protective hydrodissection with 40-80 mL of 5% dextrose or distilled water to safeguard critical structures. Under real-time ultrasound guidance, the trans-isthmic approach is employed for needle placement. Ablation is performed at 30-40 W (RFA) or 35-50 W (MWA) using the moving-shot technique. Complete nodule devascularization is confirmed by contrast-enhanced ultrasound (CEUS) during post-ablation assessment, with immediate supplementary ablation being performed if residual enhancement is identified. Clinical and sonographic follow-up is conducted at 1, 3, 6, and 12 months to assess volume reduction ratio, symptom relief, and cosmetic outcomes. The protocol also details the patient selection criteria, technical nuances for cystic/solid nodules, and management of intraoperative complications. This comprehensive guide aims to optimize the reproducibility, safety, and efficacy of thermal ablation for benign thyroid nodules, serving as a practical reference for clinicians adopting these minimally invasive techniques.

Introduction

Thyroid nodules are a prevalent clinical condition, with detection rates increasing significantly due to advancements in imaging techniques, reaching up to 70% in high-frequency ultrasound (US) screenings¹. While the majority (approximately 90%) are benign and asymptomatic, some benign nodules may cause compressive symptoms, neck discomfort, or cosmetic concerns, warranting therapeutic intervention². Surgical resection, though effective, is associated with significant drawbacks, including surgical trauma, permanent hypothyroidism, and suboptimal aesthetic outcomes³.

Image-guided thermal ablation, particularly radiofrequency (RFA) and microwave ablation (MWA), has become a preferred minimally invasive alternative for selected benign nodules, offering comparable efficacy to surgery with fewer complications⁴. RFA generates heat through high-frequency alternating current that causes ionic agitation in tissue, resulting in frictional heating and coagulative necrosis. MWA operates at higher electromagnetic frequencies, inducing rapid water molecule rotation that produces more uniform and penetrative heating⁵. While RFA is better suited for small nodules near critical structures due to its precise controllability, MWA's deeper penetration makes it particularly effective for larger or hypervascular lesions^6,7.

Appropriate patient selection is critical. According to multiple guidelines^8,9, candidates for thermal ablation must fulfill all of the following essential criteria: (1) US findings suggestive of a benign nodule, with cytopathology (Bethesda II) or histopathological confirmation; (2) No history of childhood radiotherapy; (3) Patient preference for minimally invasive treatment after informed consent, or refusal of surgery/active surveillance. Additionally, at least one of the following must apply: (1) Hyperthyroidism caused by autonomous functioning nodules; (2) Nodule-related symptoms (discomfort, pain, or compressive sensation) or cosmetic concerns; (3) Recurrent or significantly enlarged nodules post-surgery. Thermal ablation is contraindicated in cases of: (1) Large substernal goiter or thyroid nodule predominantly located in the retrosternal space (For patients' ineligible for surgery/anesthesia, staged ablation or palliative treatment may be considered); (2) Contralateral vocal cord dysfunction; (3) Severe coagulation disorders; (4) Major organ dysfunction.

Despite the growing adoption of RFA and MWA for benign thyroid nodules, procedural standardization remains inconsistent across institutions, with variations in technical parameters (e.g., power settings) and perioperative assessments. Such heterogeneity may compromise clinical outcomes and hinder comparative evaluations. Therefore, this study systematically elucidates the clinical application of RFA and MWA, with emphasis on a standardized protocol to enhance reproducibility and safety.

Protocol

The protocol in this article describes standard clinical practice. No permission from the ethical committee was needed. All participants provided written consent for the use of identifiable images or clinical data in this publication.

1. Preoperative evaluation and preparation

1. Confirming cytological diagnosis
   1. Perform a fine needle aspiration (FNA) biopsy preoperatively and obtain a cytological diagnosis of a definite benign nodule.
2. Complete preoperative examinations
   1. Conduct routine tests, including complete blood count, coagulation profile, liver and kidney function tests, and electrocardiogram.
   2. Assess thyroid function (TSH, FT3, FT4, Tg, etc.).
   3. Perform thyroid and cervical lymph node ultrasound, and record the location, size, and blood flow of the nodules to be ablated.
   4. If necessary, conduct contrast-enhanced CT scans to evaluate lesion extent and anatomical relationships.
   5. Assess bilateral vocal cord mobility and function using transcutaneous US, which provides real-time evaluation during phonation and respiration. Reserve laryngoscopy for patients with hoarseness, prior neck surgery, or nodules adjacent to critical structures (e.g., recurrent laryngeal nerve course). Check for symmetry, range of motion, and any signs of paralysis or paresis.
3. Evaluating patient's overall condition
   1. Obtain a detailed medication history, specifically inquiring about anticoagulant or antiplatelet drugs (e.g., aspirin, warfarin, clopidogrel).
   2. Explain the necessity of discontinuing these medications and provide specific instructions on withdrawal timing.
4. Determining individualized treatment plan
   1. While RFA and MWA exhibit theoretical differences in penetration depth and heat-sink effects, their clinical applications frequently overlap⁶. Determine the optimal ablation modality through a comprehensive evaluation of nodule characteristics (size, location, and vascularity) and patient-specific factors¹⁰. The final decision should integrate preoperative findings, patient preferences, operator expertise, and device availability through shared decision-making.
   2. Discuss the treatment plan thoroughly with the patient and family, ensure they fully understand the risks and expected outcomes of the procedure, and obtain written informed consent.
5. Preoperative instructions
   1. Advise female patients to avoid scheduling the procedure during menstruation.
   2. Ask patients to fast for at least 4 h before and after the procedure.
   3. Establish intravenous access for medication administration.
      1. Prepare intravenous access by disinfecting the skin with povidone-iodine, inserting an 18G-20G catheter into the antecubital or dorsal hand vein under aseptic conditions, and securing it with a transparent dressing.

2. Operational procedure

1. Preparation
   1. Position the patient supine with hyperextended neck using a shoulder roll, then slightly flexed to expose the anterior cervical region.
   2. Disinfect the skin from the mandibular angle superiorly to the sternal notch inferiorly, and laterally to the anterior borders of both sternocleidomastoid muscles. Use povidone-iodine with concentric circular motions moving outward from the planned puncture site.
   3. Place a fenestrated drape centered over the thyroid cartilage. Extend drapes to cover the entire sterilized area, including chin, chest, and lateral neck.
   4. Position the ultrasound probe within a sterile sheath and secure cable away from the operative field.
   5. Have the operator sit beside the patient's head.
2. Contrast-enhanced ultrasound (CEUS)
   1. Using a high-frequency linear array transducer (7-15 MHz), systematically survey the nodule by rotating the probe 90° between transverse and longitudinal planes to ensure complete coverage of both the nodule and surrounding parenchyma.
   2. Locate the hypoechoic nodular margin on B-mode ultrasound and confirm vascular distribution using color Doppler to identify the nodule's maximal cross-sectional plane, avoiding major vessels exceeding 2 mm in diameter.
   3. Select the optimal ablation plane where the nodule occupies over 50% of the ultrasound screen width, keep critical structures like the trachea and carotid sheath at least 5 mm clear of the nodule margin, and use Doppler imaging to verify the needle path avoids major vessels.
   4. Obtain a complete view of the nodule and surrounding normal thyroid parenchyma, hold the probe still, instruct the patient to avoid swallowing, and then switch the transducer to harmonic CEUS mode. Always position the focus slightly deeper than the target nodule.
   5. Prepare the ultrasound contrast agent by reconstituting the vial containing 25 mg of lyophilized powder with 5 mL of normal saline according to the manufacturer's instructions. Vigorously shake the vial for 20 s until a homogenous milky suspension is obtained (final concentration: 5 mg sulfur hexafluoride/mL). For each injection, administer 1.2-2.4 mL of the suspension (6-12 mg of microbubbles) as a rapid bolus through an antecubital vein, followed immediately by 5 mL of saline flush at the same injection rate.
      NOTE: The ultrasound contrast agent is SonoVue, which is a sulfur-hexafluoride-filled microbubble encapsulated by a flexible phospholipid shell¹¹.
   6. Start the timer on the machine immediately. Monitor the dynamic perfusion process in real time for the initial 60 s post-injection to capture peak vascular enhancement, followed by intermittent scanning (e.g., every 15-20 s) until 120 s to assess late-phase washout.
      1. Maintain a mechanical index (MI) below 0.30 and minimize probe pressure during CEUS to reduce microbubble destruction and tissue harmonics.
3. Anesthesia
   NOTE: Pain during ablation mainly arises from the thyroid capsule due to its rich innervation by sympathetic and vagal pain fibers¹².
   1. Perform the operation under local anesthesia. Adjust the anesthesia method based on the patient's condition and pain tolerance, selecting alternatives such as local nerve block, intravenous general anesthesia, or acupuncture-combined anesthesia to ensure better patient cooperation.
   2. Under ultrasound guidance, use a syringe to infiltrate 2% lidocaine locally between the anterior thyroid capsule and anterior cervical muscles, targeting the space according to the lesion's location.
   3. Inject until an anechoic separating band forms between the thyroid gland and strap muscle.
4. Protective hydrodissection
   1. Under real-time ultrasound guidance, perform hydrodissection by injecting 40-80 mL of normal 5% dextrose or distilled water (with optional 0.5 mg epinephrine) through an 18G hydrodissection needle.
      NOTE: For RFA, avoid normal saline due to its ionic conductivity, which may interfere with RF current propagation. Non-ionic solutions (e.g., 5% dextrose) are preferred to maintain ablation efficacy. For MWA, normal saline is acceptable due to the non-electric mechanism of microwave ablation.
   2. Have the operator control needle placement while the assistant slowly injects the hydrodissection fluid (5% dextrose or distilled water for RFA; normal saline for MWA) into these anatomical spaces: between the thyroid lateral capsule and carotid sheath, between the posterior capsule and esophagus/trachea, between the thyroid and parathyroid glands, and along the recurrent laryngeal nerve course, always maintaining ≥ 5 mm safety margins (adjusted according to tumor location) to protect the carotid artery, internal jugular vein, vagus nerve, esophagus, trachea, parathyroid glands and recurrent laryngeal nerve from thermal damage.
5. Ablation procedure
   1. Use an 18G microwave antenna or RF electrode. Set the ablation output power within the following ranges: 30-40 W for RFA and 35-50 W for MWA, adjusting based on nodule size, vascularity (higher power for hypervascular or large nodules), and manufacturer recommendations. Operators prefer lower power for nodules adjacent to critical structures to mitigate thermal injury risks.
   2. Intensively monitor the patient's vital signs throughout the procedure. Record the ablation time duration, power, and total energy. Tailor the ablation strategy according to the structural heterogeneity (proportion of solid versus cystic components) of benign thyroid nodules, as detailed in the following sections.
   3. Ablation of solid or predominantly solid nodules
      1. Begin the ablation procedure by first identifying the maximal cross-sectional plane of the target nodule.
      2. Carefully plan needle trajectories under real-time US guidance with color Doppler to avoid critical structures, including major vasculature, the trachea, and nerves.
      3. Select the optimal access route based on safety and proximity, prioritizing the trans-isthmic approach for needle insertion (microwave antenna or RF electrode) to reach the deep distal margin of the benign thyroid nodules. Resort to the lateral cervical approach only when the trans-isthmic route proves unsafe or technically unfeasible.
      4. To initiate ablation, step on the foot pedal; tissue vaporization occurs within seconds, manifesting as a hyperechoic zone with microbubbles that create characteristic acoustic shadowing.
      5. As the echogenic area develops, gradually withdraw the applicator in 3-5 mm increments along the insertion tract to achieve contiguous ablation. Proceed with the moving-shot technique across three-dimensional planes. First, systematically cover the initial transverse plane by positioning the applicator concentrically from deep-to-superficial and distal-to-proximal aspects. Then, sequentially ablate in sagittal and coronal planes by dynamically adjusting the ultrasound probe.
      6. Continue each ablation cycle until the entire nodule shows uniform hyperechogenicity, ensuring complete overlap between the ablation zone and the original nodular dimensions.
      7. Upon completion of ablation, slowly withdraw the ablation needle while monitoring for any bleeding or tissue trauma under real-time ultrasound guidance.
      8. For nodules with focal anechoic (fluid-filled) regions. First, aspirate the liquid component using a hydrodissection needle. Then, perform immediate ablation as described in step 2.5.31-2.5.3.7.
   4. Ablation of predominantly cystic nodules
      NOTE: For thyroid nodules with substantial anechoic (cystic) regions, perform US-guided aspiration using a hydrodissection needle before initiating ablation therapy.
      1. Under US guidance, the operator positions the hydrodissection needle while the assistant aspirates through the attached syringe. Aspirate the intra-cystic fluid completely while maintaining continuous needle tip visualization. If the fluid is thin and clear, proceed with direct aspiration until the cyst is fully evacuated.
      2. When encountering highly viscous fluid refractory to aspiration, irrigate repeatedly with normal saline through the same needle to reduce viscosity. Continue this aspiration-irrigation cycle until obtaining clear, serous fluid, indicating a complete evacuation of colloidal or hemorrhagic content.
      3. If viscosity persists, inject alpha-chymotrypsin (4,000-5,000 U in 2-5 mL of normal saline) or urokinase (10,000-50,000 U in 2-5 mL of normal saline) into the cyst cavity, wait 5-10 min for enzymatic action, then resume aspiration. Repeat the irrigation-aspiration cycle until obtaining clear, serous fluid.
      4. Perform continuous irrigation-aspiration cycles using absolute ethanol on the cyst cavity, maintaining a 2 min dwell time per cycle to ensure thorough contact between the ethanol and the endothelial cells on the cyst wall. The operator maintains needle positioning under imaging guidance throughout the procedure while the assistant performs synchronized saline and ethanol irrigation and aspiration through the same access.
      5. Distend the cyst cavity by saline infusion through the hydrodissection needle.
      6. After completing protective hydrodissection, immediately initiate targeted ablation of the residual solid components following the protocol specified in step 2.5.3.1-2.5.3.6.
      7. Before each needle tip repositioning, infuse normal saline via the hydrodissection needle to adequately distend the cyst cavity. After adjusting the needle orientation, aspirate the saline and proceed with cyst wall ablation. Repeat this cycle iteratively to ensure complete cyst wall ablation.
         NOTE: It is critical to avoid introducing gas into the cyst cavity during this procedure, as gas may significantly impair ultrasound visualization.
      8. Have an assistant slowly re-inject saline into the cyst cavity to achieve sufficient distension, then immediately perform CEUS imaging as detailed in step 2.2.
      9. Perform CEUS immediately after completing ablation. CEUS clearly delineates the non-perfused ablation zone (Figure 1A), and if residual enhancement is detected (indicating incomplete ablation), promptly perform targeted supplementary ablation (Figure 1B). Notably, contrast extravasation (with higher sensitivity than conventional US) suggests an active hemorrhage.
      10. Completely aspirate the saline, then inject 2 mL of lauromacrogol (a widely used sclerosing agent)¹³ into the cyst cavity. This completes the combined ultrasound-guided ablation and sclerotherapy for the predominantly cystic thyroid nodule.
6. Postoperative instructions
   1. After ablation, transfer the patient to the observation room for 2 h of continuous monitoring. Maintain firm neck compression with sterile dressing for 30 min to prevent bleeding, while assessing verbal responsiveness hourly by asking direct questions (e.g., Rate your neck pain from 1 to 10).
   2. Record vital signs at 30 min intervals, watching for blood pressure fluctuations >20 mmHg or SpO₂ drops >5%. Actively check every 15 min for voice changes (have the patient count 1-10 aloud), new-onset dyspnea, or neck swelling.
   3. Only clear for discharge when all criteria are met: stable puncture site for 1 h, normal phonation confirmed by two staff members, and vital signs within 10% of pre-procedure baselines.
7. Follow-up protocol and outcome measurement
   1. Patients underwent clinical assessments at 1, 3, 6, and 12 months post-procedure, followed by semi-annual to annual evaluations. Assessments encompassed three key parameters: neck circumference measurement, symptomatic evaluation using scoring systems, and objective cosmetic grading.
   2. The primary efficacy endpoint was volume reduction ratio (VRR), quantitatively evaluated through US or CEUS imaging. The VRR was calculated as the percentage decrease in nodule volume relative to baseline, expressed by the formula:
      VRR (%) = (pretreatment volume - follow-up volume)/pretreatment volume x 100%
   3. Nodule volumes were derived from orthogonal diameter measurements using the ellipsoid approximation formula:
      Volume = π/6 x d1 x d2 x d3,
      where d1 represents the maximum nodule diameter, and d2 and d3 denote the two perpendicular diameters.

Results

The clinical characteristics of the enrolled patients are summarized in Table 1.

The volume of the nodules treated with ablation was 8.3 mL (5.0-11.2 mL) at baseline, 4.6 mL (2.6-7.0 mL) at 1 month, 3.5 mL (2.0-5.6 mL) at 3 month, 2.5 mL (1.5-4.3 mL) at 6 month, 1.1 mL (0.5-1.8 mL) at 12 month, and 0.9 mL (0.3-1.6 mL) at the last follow-up period (Table 2). The nodules exhibited a time-dependent volume reduction pattern, showing significant decreases relative ...

Discussion

This study details an optimized ablation protocol where RFA or MWA procedures are dynamically guided by real-time ultrasonography for benign thyroid nodule management. Our protocol's applicability to both RFA and MWA is supported by their shared procedural principles. The primary distinction lies in the ablation device (radiofrequency electrode versus microwave antenna) and power settings, while all other procedural steps, including CEUS-guided assessment, protective hydrodissection, and moving shot technology, remai...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Absolute ethanol	Sigma-Aldrich	459836	sclerotherapy
Hydrodissection needle	BD (Becton, Dickinson and Company)	20G Insyte	hydrodissection
Lauromacrogol	Shaanxi Tianyu Pharmaceutical Co., Ltd.	10ml	sclerotherapy
Lidocaine	Shanghai Harvest Pharmaceutical Co., Ltd.	0.1g, 5ml	local anethesia
Microwave ablation antenna	Nanjing Great Wall Medical Equipment Co., Ltd.	G-18-10	microwave ablation
Microwave ablation apparatus	Nanjing Great Wall Medical Equipment Co., Ltd.	MTI-5AT	microwave ablation
Radiofrequency applicator	Olympus Surgical Technologies	CelonProSurge, micro-100-T15	radiofrequency ablation
Radiofrequency device	Olympus Surgical Technologies	CelonLabPOWER	radiofrequency ablation
Saline solution	Anhui Shuanghe Pharmaceutical Co., Ltd.	100ml	isolation fluid
Saline solution at room temperature or 4°C	Shandong Lukang Chenxin Pharmaceutical Co., Ltd.	500ml	serving as a cooling fluid to reduce the probe tip temperature during ablation
SonoVue	Bracco	-	CEUS agent
Syringe	Shandong Weigao Group Medical Polymer Co., Ltd.	5ml	local anethesia
Syringe	Shandong Weigao Group Medical Polymer Co., Ltd.	20ml	skin dilation; isolation solution injection
Ultrasound machine	Sonoscape Medical Corp.	E5 series	ultrasound guidance