Precise liver tumor ablation: the clinical potential of US-US overlay fusion guidance

Article information

Ultrasonography. 2024;43(6):407-412

Publication date (electronic) : 2024 August 13

doi : https://doi.org/10.14366/usg.24133

Yasunori Minami

Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan

Correspondence to: Yasunori Minami, MD, PhD, Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi Osaka-sayama, Osaka 589-8511, Japan Tel. +81-72-366-0221 (ext. 3149) Fax. +81-72-367-2880 E-mail: minkun@med.kindai.ac.jp

Received 2024 July 18; Revised 2024 August 9; Accepted 2024 August 13.

Abstract

Introduction

Curative care refers to treatments aimed at curing cancer, with surgical resection being the recommended approach for patients with early-stage hepatocellular carcinoma (HCC), according to current international and local guidelines on HCC management [1-4]. However, HCC often develops in patients with liver cirrhosis, complicating treatment due to the presence of tumors and the compromised state of the remaining liver tissue. When surgery is not feasible because of impaired liver function, thermal tumor ablation, a minimally invasive technique, is performed.

Ablation is a treatment method that effectively destroys cancer cells while preserving the surrounding liver tissue. Various ablation techniques, such as radiofrequency ablation (RFA) and microwave ablation, are performed under precise image guidance. Research has shown that ablation therapies lead to improved clinical outcomes in terms of survival rates; however, they are associated with a significantly higher risk of local recurrence [5-10]. Specifically, local recurrence rates are higher in patients with HCC tumors larger than 2 cm compared to those with smaller tumors [11]. During the ablation process, bubbles generated can create artifacts that obscure the tumor and the ablation zone, complicating the visualization of the lesion's contours. Therefore, these ultrasound (US) artifacts adversely affect the evaluation of ablative margins both during and immediately after the procedure. For ablation to be considered technically successful, the ablation zone must encompass both the tumor and a minimum safety margin of at least 5 mm [12,13]. However, achieving complete ablation of HCC with an adequate safety margin proves to be more challenging in tumors measuring >2 cm.

Residual tumor cells may remain in an insufficient ablative marginal zone, leading to a high risk of tumor progression in patients with HCC [14-17]. This risk can be mitigated by employing a three-dimensional (3D) assessment of the ablative margin, which offers a more objective and accurate method for evaluating the technical success of ablation. Recent advancements in image fusion technology now allow for a 3D evaluation of the ablative margin both during and immediately after the ablation procedure. Additionally, the ablative margin can be assessed side-by-side, and on US, it can be visualized using US-US overlay fusion to highlight the difference between the ablative hyperechoic zone and the marked tumor border [18-20]. Therefore, the US-US fusion guidance technique is gaining increasing attention as it enables operators to perform thermal ablation procedures with greater confidence and precision by monitoring the ablation zone.

The US-US fusion guidance technique and its current clinical applications for hepatic interventions are reviewed herein.

Applications and Settings for US Fusion Imaging

Real-time virtual sonography (Hitachi, Tokyo, Japan) represents a significant advancement in the field of fusion imaging. Other image fusion platforms used in clinical settings include Volume Navigation (v-nav; GE Healthcare, Waukesha, WI, USA), Smart Fusion (Canon Medical Systems, Tokyo, Japan), eSie Fusion Imaging (Siemens Healthcare, Erlangen, Germany), PercuNav (Philips, Andover, MA, USA), and S-Fusion (Samsung Medison, Seoul, Korea).

The flowchart in Fig. 1 illustrates the set-up used for US-US fusion guidance and the associated procedure. Initially, the liver is manually scanned in a sweeping motion before ablation to capture the US volume in 3D. This scanning area must encompass both the tumor and the surrounding intrahepatic vessels to facilitate image adjustments. Subsequently, the tumor is highlighted with a color to delineate blurred or complex boundaries. Techniques such as spherical marker and tumor-border tracing are utilized to mark the 3D US volume of the tumor. In the spherical marker technique, the tumor's center is clicked on a two-dimensional (2D) image to represent the cycle, allowing adjustments to the tumor's size and location, including those with irregular shapes. Alternatively, for tumors with unusual shapes, once the border has been traced in 3D using v-nav, the tumor can be colorized.

Fig. 1.

Flowchart showing the set-up used for ultrasound (US)-US overlay fusion.

To assess the ablative margin in real-time, image fusion is initiated immediately after ablation. Manual point registrations are performed for intrahepatic landmarks (Fig. 2A), and this process may be repeated until optimal registration is achieved. A real-time 2D US image (post-ablation) and a multiplanar reconstruction (MPR) of the US image (pre-ablation) are displayed side by side. US-US overlay fusion projects an image of the tumor onto the ablative hyperechoic zone, allowing for identification of the ablative margin on US. If an insufficient ablation site is identified (Fig. 2B), a subsequent ablation may be attempted for overlap (Fig. 2C). An adequate ablative margin is then achieved in 3D using US-US fusion guidance (Fig. 2D) [18-21].

Fig. 2.

Illustrations of the process and procedure of ultrasound (US)-US fusion guidance.

A. A cross-sectional image of the three-dimensional US volume before ablation is shown on the right, with the tumor colored in green. The ablative hyperechoic zone due to ablation on real-time US is shown on the left. A gap between two US images may occur even immediately after ablation because of liver rotation. B. The tumor image is projected onto the ablative hyperechoic zone (left). Therefore, the site of an insufficient ablative margin (arrow) is identified. C. An ablation needle is placed at the site of the insufficient ablative margin (arrow). D. US-US overlay fusion shows a green hepatocellular carcinoma inside the ablative hyperechoic zone concentrically (left). The ablative margin is visualized as the difference between the ablative hyperechoic zone and the marked tumor border.

Is the Entire Ablative Hyperechoic Zone Regarded as a Necrotic Lesion after Ablation of the Liver?

Thermal ablation produces a transient hyperechoic zone that is approximately spherical and extends outward from the active electrode tip. This hyperechoic response results from the formation of microbubbles as water in the heated tissue vaporizes. Clinicians may use this hyperechoic zone as a rough indicator of the extent of tumor destruction [22]. Previous studies have compared ablation zones in US images with those in excised specimens. The results suggested that the echogenic response tends to overestimate the diameter of necrosis at the millimeter level [14,23]. Conversely, other studies have indicated an underestimation of this measurement [24,25]. However, these studies did not evaluate the same cross-sections.

With current developments in imaging, US image fusion technology allows accurate evaluations of the ablative margin at the millimeter level. Therefore, further research is necessary to determine if the entire ablative hyperechoic zone observed after RFA of the liver should be classified as a necrotic lesion. In one study, the sizes of ablation zones within the same cross-section were compared using B-mode US and a combination of contrast-enhanced US (CEUS) and computed tomography (CT) through a series of US examinations [26]. The correlation coefficients (r-values) were 0.99 and 0.98 for the long and short dimensions, respectively, between B-mode US and CEUS. Additionally, the r-values were relatively high, at 0.96 and 0.92 for the long and short dimensions, respectively, between B-mode US and contrast-enhanced CT. These findings indicate a strong correlation, confirming that the ablative hyperechoic zone is practically equivalent to an avascular necrotic lesion.

In a study using a phantom-simulated liver tumor ablation model [27], the registration success rate and the accuracy rate of the evaluation were both 100%. The assessment time was 3.8±0.9 minutes and the measurement error was 1.1±0.6 mm.

Evidence Supporting the Efficacy of the US-US Fusion Guidance Technique for Ablation

Real-world data indicate that the rate of achieving a 5-mm safety margin using conventional ablation techniques varies from 3% to 40% [28-31]. The US-US overlay fusion guidance has been demonstrated to effectively achieve a safety margin at a rate of 86.8% (Fig. 3) [19]. In a comparative study, the rate of achieving a 5-mm safety margin for HCC nodules was 89.3% with the US-US overlay fusion technique compared to 47.0% with conventional guidance (P<0.01) [20]. Additionally, the 2-year local tumor progression rate was significantly lower with the US-US overlay fusion technique (0.8%) than with conventional guidance (6.0%) (P=0.022) [20]. The technical success rate ranged from 81.3% to 100% [32,33]. A systematic literature review of 22 studies found that the technical effectiveness rate during the first follow-up varied from 89.3% to 100% [32].

Fig. 3.

Hepatocellular carcinoma (HCC) in a 52-year-old man in segment IV.

A. At planning ultrasound (US) examination with fusion imaging, there was a hypoechoic nodule (arrow) with irregular borders in the liver (left) at the corresponding site of the fused arterial-phase magnetic resonance image (right). B. Under B-mode US guidance, a radiofrequency electrode (arrowhead) was placed in the center after penetrating the target lesion. C. The right side shows a cross-sectional image of a threedimensional US volume before ablation, with the yellow circle (1V) onto the HCC. The left side presents an image of US-US overlay fusion showing the yellow circle inside the ablative hyperechoic zone.

The US-US fusion guidance technique has increased our confidence in obtaining sufficient ablative margins for larger HCCs. Previous studies have reported very low local tumor progression rates for HCCs >2 cm [19,20]. Therefore, the US-US fusion guidance technique has the potential to improve the local controllability of ablation in patients with HCCs >2 cm.

Tips for Ablation with the US-US Fusion Guidance Technique

Conclusion

An image fusion technique has been developed for treating HCC, enhancing the confidence of operators performing ablation. This technique utilizes real-time US-CT/magnetic resonance imaging fusion to guide ablation by identifying liver malignancies that conventional US fails to detect. Although fusion imaging guidance has improved the clinical effectiveness of ablation for HCC, the risk of local recurrence remains higher compared to surgical resection. Accurate, real-time assessments of the ablation zone are crucial for reducing this risk. The US-US overlay fusion significantly enhances 3D evaluations of the HCC ablative margin with high accuracy. Additionally, CEUS can be integrated with fusion imaging in challenging cases. Ablation guided by US-US fusion has been associated with higher recurrence-free survival rates and lower rates of local tumor progression, suggesting its potential to contribute to "precise ablation" in future applications.

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Notes