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.

Electroporation (EP) is widely used in medicine, such as cancer treatment, in form of electrochemotherapy or irreversible electroporation (IRE). For EP device testing, living cells or tissue inside a living organism (including animals) are needed. Plant-based models seem to be a promising alternative to substitute animal models in research. The aim of this study is to find a suitable plant-based model for visual evaluation of IRE, and to compare the geometry of electroporated areas with in-vivo animal data. For this purpose, a variety of fruit and vegetables were selected and visually evaluated after 0/1/2/4/6/8/12/16/24 h post-EP. Apple and potato were found to be suitable models as they enabled a visual evaluation of the electroporated area. For these models, the size of the electroporated area was determined after 0/1/2/4/6/8/12/16/24 h. For apples, a well-defined electroporated area was visual within two hours, while in potatoes it reached a plateau after eight hours only. The electroporated area of apple, which showed the fastest visual results was then compared to a retrospectively evaluated swine liver IRE dataset which had been obtained for similar conditions. The electroporated area of the apple and swine liver both showed a spherical geometry of comparable size. For all experiments, the standard protocol for human liver IRE was followed. To conclude, potato and apple were found to be suitable plant-based models for the visual evaluation of electroporated area after irreversible EP, with apple being the best choice for fast visual results. Given the comparable range, the size of the electroporated area of the apple may be promising as a quantitative predictor in animal tissue. Even if plant-based models cannot completely replace animal experiments, they can be used in the early stages of EP device development and testing, decreasing animal experiments to the necessary minimum.

Hepatocellular carcinoma is a leading cause of cancer-related death in many parts of the world. Traditional treatment options are not always effective. During the promising minimally invasive electroporation-based therapies, biological cell membranes are exposed to an external, sufficiently high, pulsed electric field which creates so-called nanopores into the lipid bilayer of the cell membrane. These pores can either be permanent (irreversible electroporation (IRE)), leading to apoptosis, or repairable (reversible electroporation (RE)), with continued cell function. In tumor therapy, RE is used to increase the diffusion of a chemotherapeutic drug during electrochemotherapy. For both IRE and RE, the success of the treatment is dependent on application of the appropriate electric field. Therefore, this study aims to define the pulse parameters and thresholds for IRE and RE on hepatocellular carcinoma (HepG2) cells in-vitro. In a custom-made in-vitro setup, HepG2 cell viability (0, 5, 10, and 15 min), and the peak temperature were measured after electroporation with the different IRE and RE pulsing protocols, to determine the most successful settings for IRE and RE. A CAM/PI flow cytometric assay was performed to confirm cell permeabilization for the RE pulsing protocols with the highest cell viability. The results indicated that an IRE pulsing protocol (70 pulses, 100 µs pulse length, and 100 ms interval) with an electric field strength of 4000 V/cm was needed as threshold for almost complete cell death of HepG2 cells. A RE pulsing protocol (8 pulses, 100 µs pulse length, and 1000 ms interval) with an electric field strength of 1000 V/cm was needed as threshold for viable and permeabilized HepG2 cells. The low peak temperatures (max 30.1°C for IRE, max 23.1°C for RE) within this study indicated that the reduction in HepG2 cell viability was caused by the applied electric field and was not a result of Joule heating.

Objectives: Irreversible Electroporation (IRE) is a non-thermal minimally invasive cancer therapy used in the treatment of liver tumors. However, the therapy entails an electrical current flux which can be high enough to cause a noticeable temperature increase. Therefore, the analysis of the heat distribution is important: during any IRE treatment, the target area is intended to be treated with non-thermal effects, where existing thermal effects should not damage nearby sensitive structures. This article aims to compare the established two parallel needles electrode setup, used by FDA-approved electroporation delivering devices, to a single needle, multiple electrode prototype design. Methods: Levels and distributions of the temperature at different distances from the applicators during an IRE liver treatment were investigated. The prototype results were collated with already published in-vivo data. All electrode configurations were analyzed numerically in COMSOL Multiphysics for different pulse protocols. Results: The extension of coagulation necrosis predicted by the model matched available in-vivo data. While the maximum average temperature during pulsation was higher for the prototype (74 °C) than for the two-needle IRE setup (57 °C), the thickness of the coagulation necrosis around the conductive electrodes was in the same range for both configurations. However, the location differed completely: the necrosis engendered by the prototype was located inside the tumor, while the two-needle IRE setup created necrosis outside the tumor, potentially closer to sensitive structures. Conclusion: The results highlighted the importance of heat distribution analysis for the design of new IRE needles as well as for IRE treatment planning. Proper analysis ensures that the non-thermal effects are maximized while minimizing any potential thermal damage to surrounding sensitive structures.

Objectives: Irreversible Electroporation (IRE) is both open surgery and minimally invasive cancer therapy used in the treatment of liver tumors. The therapy demands precision and accuracy to ensure complete tumor ablation. Reliable simulation tools can help achieve this goal by predicting the tissue regions that will reach the required electric field threshold and by suggesting correcting actions when the predicted outcome is inadequate. This article retrospectively compares segmented ablations from intra-procedural computed tomography (CT) scans with computer simulations to check their validity in predicting the operation outcome and the required electric field threshold. Methods: 10 patient ablation procedures were retrospectively analyzed using a detailed computational model of electroporation, informed by the patient-specific geometry of each case. CT scans were analyzed by three physicians over two sessions to assess intra- and inter-observer variability. Same day postoperative images were used for accuracy. The resulting measured ablations from the patient's data were compared to simulation predictions, both in terms of ablated volumes and 3D similarity scores (Dice coefficient). Results: Simulated ablation volumes were computed across electric field thresholds (465-750 V/cm), showing highest volumes at 465 V/cm and lowest at 750 V/cm. Comparison with physician segmented volumes showed best match for 500-600 V/cm ablation threshold: this result was consistent across different patients despite differences among patient's conditions and characteristics. 3D analysis revealed Dice scores between 0.63 and 0.77 (mean: 0.71), indicating moderate to good agreement. Visual and statistical comparisons further validated the reliability of the simulation model within this threshold range. Conclusion: This study highlighted the accuracy of IRE ablation volume predictions by comparing retrospective CT based ablation volume segmentations with electric field simulations. The best match occurred at 500 to 600 V/cm thresholds, with post-procedure measurements. Despite observer variability and modeling limitations, Dice scores showed moderate to good agreement, validating the simulation model and emphasizing timely imaging for accuracy.

Plant-based models can reduce the number of animal studies for electroporation research in medical cancer treatment modalities like irreversible electroporation. Magnetic resonance imaging (MRI) provides volumetric visualisation of electroporated animal or plant tissues; however, contrast behaviour is complex, depending on tissue and sequence parameters. This study numerically analysed contrast between electroporated and non-electroporated tissue at 1.5 T in various MRI sequences (DWI, T1W, T2W, T2*W, PDW, FLAIR) performed 4 h after electroporation in apples (N = 4) and potatoes (N = 8). Sequence parameters (inversion time [TI], echo time [TE], b-value) for optimal contrast and electroporation-mediated changes in T1 and T2 relaxation times and apparent diffusion coefficient (ADC) were determined for potato (N = 4) using quantitative parameter mapping. FLAIR showed the electroporated zone in potatoes with best contrast, whereas no sequence yielded clear visibility in apples. After electroporation, T1 and T2 in potato decreased by 29% ([1245 ± 54 to 886 ± 119] ms) and 12% ([249 ± 17 to 217 ± 12] ms), respectively. ADC increased by 11% ([1303 ± 25 to 1449 ± 28] × 10-6 mm²/s). Optimal contrast was found for TI = 1000 ms, low TE and high b-value. T1 was most sensitive to EP-mediated tissue changes. Future research could use this methodology and findings to obtain high-contrast MR images of electroporated and non-electroporated biological tissues.