Applications of Elastography in Ablation Therapies: An Animal Model In Vivo Study

Introduction

Ablation therapies were positioned as one of the main local treatments for solid organ tumors, especially renal and hepatic tumors.^1,2 There are many modalities of ablation therapies (Table 1). The most commonly used are radiofrequency ablation (RFA), microwave ablation (MWA),^3,4 and LASER ablation (light amplification by stimulated emission of radiation) (LA), as an option for small tumors. ⁵ Different types of ablation systems are emerging in recent years, such as irreversible electroporation or high-intensity focused ultrasound.

After applying any ablation therapy, a latency time of around 45 days should be waited before performing an imaging study and check the results. In case of an unfavorable result, a new therapy session could be applied. All this waiting period could potentially represent wasted time that becomes fundamental in oncological patients. This situation highlights the need for an immediate postablation control. Elastography could represent a valuable method for the evaluation of the ablation efficacy, since it allows a real-time and objective assessment of the elasticity of the tissues.

Objectives

To determine short-term in vivo tissue changes after the application of ablation systems using different diagnostic imaging methods.

Materials and Methods

Ablation systems

We used the following ablation systems (Fig. 1):

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FIG. 1.

Ablation systems. (A) LA system, (B) MWA (green arrow), and RFA system (red arrow). (C) Optic fiber used in LA (blue arrow). (D) Antenna and electrode used in MWA (black arrow) and RFA (pink arrow). LA, laser ablation; MWA, microwave ablation; RFA, radiofrequency ablation.

- RFA System (Cool-tip™ RF Ablation System E Series Medtronic) using a variable power (according to the impedance of the tissue), during 6 minutes, reaching an average temperature of 63.7°C through an electrode 15 cm long and 17 G, with an ablation diameter of 2 cm.

- MWA System (Evident™ MW Ablation System Medtronic) using a power of 75 W, for 4 minutes, by means of an antenna 15 cm long and 15 G, with an ablation diameter of 2 cm.

- LA System (EchoLaser with laser cooled device; Elesta, Calenzano, Italy) using a power of 12 W, for 5 minutes and 30 seconds, by means of a 25 cm optical fiber inserted with a 17 G carbon-fiber needle.

Imaging systems

We used the following medical imaging systems (Fig. 2):

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FIG. 2.

Medical imaging systems used. CT, computed tomography; LA, laser ablation; MWA, microwave ablation; RFA, radiofrequency ablation; US, ultrasound.

- Ultrasound (US) equipment (ACUSON S3000 Ultrasound System Siemens Healthineers, Germany) with convex abdominal transducer 1.5–6 MHz.

- Computed tomography (CT) (SOMATOM AS Definition Siemens Healthineers, Germany).

- Elastography System (Virtual Touch™ Healthineers Siemens, Germany) using a laparoscopic ultrasound (LUS) probe (Laparoscopic Ultrasound Probe; Siemens, Germany) of 3.5 MHz, with a length of 376 cm, a mobile head length of 65 cm, and a diameter of 1 cm, together with a laparoscopic column (IMAGE1 S CONNECT and AIDA™ Karl Storz—Endoskope, Germany). Liver fibrosis was determined according to the criteria of the METAVIR scale.^6,7

Workflow

All the procedures were performed in an operating room; the animal was placed in dorsal decubitus, using general anesthesia with constant controls of vital parameters, and sterile technique. Under imaging guidance (US and CT), we placed the ablation probes (RFA electrode in the right lobe of the liver, MWA antenna in the middle lobe, LA optic fiber in the left lobe) (Fig. 3). We ablated the selected regions and removed probes after the procedure. The same tasks were repeated in the kidneys. The final step was the ablation zone scan using US, CT, and elastography by the LUS approach.

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FIG. 3.

Placement of ablation needles inside the organs. (A, B) Carbon needle placement using US guidance. (C, D) Carbon needle placement using CT-guidance. CT, computed tomography; US, ultrasound.

The animal was sacrificed according to protocol. A laparotomy and a macroscopic examination of the ablation areas were performed.

Results

All the animals survived the procedures. No major intraoperative complications were documented. A session of each type of ablation (RFA, MWA, and LA) was performed on the liver and kidneys of each pig. Two cases of “popcorn effects” were reported for MWA of the liver (Fig. 4).

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FIG. 4.

“Popcorn effects” after application of liver microwave ablation.

A session of each type of ablation (RFA, MWA, and LA) was performed on the liver and kidneys of each pig. The characteristics of each procedure were determined (Table 2). MWA was faster than the other types of ablation therapies.

The imaging studies obtained from the ablation zones were compared with the results of the elastography and with the macroscopic examination (Fig. 5). A central and peripheral ablation zone was determined, surrounded by healthy tissue. These well-limited areas were observed. The largest diameter of the ablation zones was measured and compared (P ≥ .05) (Table 3). The largest was MWA, the smallest was LA. The correlation between the ablated areas and the elastographic images was also analyzed. It was observed macroscopically that the zone of central and peripheral ablation and of the surrounding normal tissue coincided with the elastographic images.

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FIG. 5.

Images after ablation. (A) US, (B) CT, (C) macroscopy, and (D) elastography. Correlation between different zones within ablation area can be observed. CT, computed tomography; CZ, central zone that corresponds to the necrotic zone; M, margin; NT, normal tissue/normal parenchyma; PZ, peripherical zone; US, ultrasound.

Discussion

Tumor ablation is a proven method for the treatment of tumors. There are different types (Table 1).^8,9 It can be used with different approaches, whether open, laparoscopic, endoscopic, or percutaneously.^10–16 Its main indications are hepatic, renal, and pulmonary lesions, among others.^16–20 The important current applications of image-guided surgery have made percutaneous ablations increasingly frequent. ¹⁹ It is likely that in the coming years, liver resections will only be performed in selected patients and ablation will become the predominant treatment.^21–23

Thermoablative therapies such as RFA, MWA, and LA destroy tumor tissue using heat.^24,25 The ablation zone presents a central sector that corresponds to coagulative necrosis (also called “white zone”) and a peripheral sector with swollen tissue and inflammatory reaction (called “red zone” of hyperemia), surrounded by healthy tissue. ⁸ This pattern was repeated in the three types of ablation therapies used in this work. Even all the imaging methods observed the same characteristics (Fig. 5).

For an ablation to have a result, its margin must reach 5–10 mm of healthy tissue surrounding the tumor. ⁸ In daily practice, it is difficult to observe this detail using US, CT, and magnetic resonance imaging (MRI) shortly after treatment. This is due to the inflammatory reaction secondary to the thermal effect. It is necessary to wait between 45 and 60 days to determine if the therapy is effective. If not, the session is repeated. This wasted time delays the treatment. This situation represents a current problem regarding immediate postablation control. With the intention of reducing this lost time, in this work, we use shear wave elastography since it allows to objectively determine the elasticity of tissues, based on their mechanical properties. ²⁶ Elasticity is the result of the quotient between the compression made against a tissue and the deformation achieved with it, called Young's modulus (soft tissues deform more than hard tissues), and its unit of measurement is as follows: m/s or kPa (higher m/s or kPa, greater fibrosis). Its principle of action uses a low-frequency wave (50 Hz) that propagates 65 mm inside the parenchyma. Propagation speed is proportional to stiffness (stiffer, faster). This technique is a method that can be used in conjunction with US and MRI. The different values obtained are expressed graphically using a color scale. The METAVIR scale is used to determine the state of liver fibrosis. It is made up of five categories: stage 0 (F0) = no fibrosis; stage 1 (F1) = mild fibrosis; stage 2 (F2) = moderate fibrosis; stage 3 (F3) = severe fibrosis; and stage 4 (F4) = cirrhosis. The correlation of this scale with the elastographic results is as follows: F0/F1 < 7 kPa, F2 < 9.5 kPa, F3 < 12.5 kPa, and F4 > 12.5 kPa.^7,27 In this preliminary work, it was observed that the elastography showed correlation with the US and CT images, and with the macroscopy. The different elastographic characteristics show that the tissues acquired after ablation could be clearly observed. The images obtained by US and CT were adequately correlated with those represented by elastography. While this is a preliminary study, we believe it has a promising future and future studies will determine whether elastography can be used in the future to determine whether ablation has been completed.

The limitations of this work are the small number of individuals involved and that it is a preliminary clinical study. Furthermore, the elastographic studies in the kidney are limited, so the results reported in this work should be interpreted preliminarily. ²⁸

Conclusion

Monitoring of the results of ablation therapies shortly after their application is possible through imaging studies. It allows determining the size of the ablation zone, its characteristics, ruling out complications, and its early result. Elastography could help meet this goal. However, microscopic studies are needed to determine the true scope of this preliminary study.