Electroporation of the Liver: More Than 2 Concurrently Active, Curved Electrodes Allow New Concepts for Irreversible Electroporation and Electrochemotherapy

Abstract

Irreversible electroporation and electrochemotherapy are 2 innovative electroporation-based minimally invasive therapies for the treatment of cancer. Combining nonthermal effects of irreversible electroporation with local application of chemotherapy, electrochemotherapy is an established treatment modality for skin malignancies. Since the application of electrochemotherapy in solid organs is a promising approach, this article describes a novel electrode configuration and field generating method. For the treatment of hepatic malignancies, the shape of the electric field should resemble a spherical 3-dimensional geometry around the target tissue inside the liver. To adapt the actual shape of the field, the probe is designed in computer-aided design with a live link to a computer simulation software: Changes in design can be revalued quickly, regarding different quality criteria for field strength inside and outside the tumor. To rate these criteria, a set of formulas with weighting coefficients has been included. As a result of this design process, a needle-shaped prototype applicator has been built, designed for an intracorporal electroporation-based treatment. It can be used as percutaneous, image-guided, minimally invasive treatment option for malignant liver tumors. The shaft of the probe is used as central electrode and fitted with additional 4 expandable electrodes. These satellite electrodes are hollow, thus serving as injectors for chemotherapeutic agents within the area of the electric field. This configuration can be used for electrochemotherapy as well as irreversible electroporation. By placing 5 electrodes with just one needle, the procedure duration as well as the radiation dose can be reduced tremendously. Additionally, the probe offers an option to adapt the field geometry to the tumor geometry by connecting the 5 electrodes to 5 individually chosen electric potentials: By fine-tuning the ablation zone via the potentials instead of adjusting the location of the electrode(s), the procedure duration as well as the radiation dose will decrease further.

Keywords: CAD design; COMSOL multiphysics; ECT; FEM; IRE; computer simulation; electric field; electrode design; hepatic cancer; minimally invasive.

Figure 1.

Correlation between the electric field strength E and the pulse width t within application of EP. Above these values, heat is generated (thermal). Modified after Dev et al.^,

Figure 2.

A, Electric field simulation for the current version of the prototype seen in Figure 3. Left: Sectional plane of the simulated electrical field distribution (static) for an applied voltage of U = 1.5 kV. Red area: E > 1.3 kV/cm, tissue in this area will be irreversibly porated (thermal ablation is also possible, especially near the electrode’s surface). Blue area: E < 0.3 kV/cm, tissue in this area will not be harmed. Area in-between: reversible EP, target area for chemotherapeutic drugs (ECT). These thresholds are estimated; thus, the areas in the image are overlapping. The exact values depend on the tissue type and the pulse protocol and will be determined experimentally. Right: Design drawing with the metrics of this simulation. B, Electric field simulations for a modified prototype with changed geometry parameters. Applied voltage U = 2 kV. Left: Y-Z-sectional plane like in Figure 2A. By changing geometry parameters, the field can adapt to specific tumor geometries (here: optimized to an almost spherical field). Right: Two X-Y-sectional planes from the left image. Changing just the wiring (without modify any geometry parameters), the field geometry also changes: Just by rotating these 2 potentials, the treatable area increases. Further improvements can be done with more than 2 different potentials. EP indicates electroporation; ECT, electrochemotherapy.

Figure 3.

Prototype for intracorporal application of IRE or ECT to malignant liver tumors, used for in vivo trials (dimensions, see Figure 2A; an earlier version of the prototype, which had nearly the doubled size, was shown in the study by Ritter et al). Complete view with drug delivery and electrical supplies. In the upper probe, the satellite electrodes are inside the shaft (for punctuation and placement); in the lower probe, the satellite electrodes are expanded. ECT indicates electrochemotherapy; IRE, irreversible electroporation.