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.

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Background So far, typical findings for COVID-19 in computed tomography (CT) have been described as bilateral, multifocal ground glass opacities (GGOs) and consolidations, as well as intralobular and interlobular septal thickening. On the contrary, round consolidations with the halo sign are considered uncommon and are typically found in fungal infections, such as invasive pulmonary aspergillosis. The authors recently observed several patients with COVID-19 pneumonia presenting with round, multifocal consolidations accompanied by a halo sign. As this may indicate alterations of CT morphology based on the virus variant, the aim of this study was to investigate this matter in more detail. Methods 161 CT scans of patients with confirmed SARS-CoV-2 infection (RT-PCR within 2 days of CT) examined between January 2021 and September 15, 2021 were included. Follow-up examinations, patients with invasive ventilation at the time of CT, and patients with insufficient virus typing for variants of concern (VOC) were excluded. CT scans were assessed for vertical and axial distribution of pulmonary patterns, degree of involvement, uni- vs. bilaterality, reticulations, and other common findings. The mean density of representative lesions was assessed in Hounsfield units. Results were compared using Mann-Whitney U-tests, Studentʼs t-rests, descriptive statistics, and Fisher’s exact tests. Results 75 patients did not meet the inclusion criteria. Therefore, 86/161 CT scans of unique patients were analyzed. PCR VOC testing confirmed manifestation of the Delta-VOC SARS-CoV-2 in 22 patients, 39 patients with Alpha-VOC and the remaining 25 patients with Non-VOC SARS-CoV-2 infections. Three patients with the Delta-VOC demonstrated multiple pulmonary masses or nodules with surrounding halo sign, whereas no patients with either Alpha-VOC (p = 0.043) or non-VOC (p = 0.095) demonstrated these findings. All three patients were admitted to normal wards and had no suspicion of a pulmonary co-infection. Patients with Delta-VOC were less likely to have ground glass opacities compared to Alpha-VOC (7/22 or 31.8 % vs. 4/39 or 10.3 %; p < 0.001), whereas a significant difference has not been observed between Delta-VOC and non-VOC (5/25 or 20 %; p = 0.348). The mean representative density of lesions did not show significant differences between the studied cohorts. Conclusion In this study 3 out of 22 patients (13.6 %) with Delta-VOC presented with bilateral round pulmonary masses or nodules with surrounding halo signs, which has not been established as a notable imaging pattern in COVID-19 pneumonia yet. Compared to the other cohorts, a lesser percentage of patients with Delta-VOC presented with ground glass opacities. Based on these results Delta-VOC might cause a divergence in CT-morphologic phenotype. Key Points: Citation Format

Background: Electroporation-based cancer treatments are minimally invasive, nonthermal interventional techniques that leverage cell permeabilization to ablate the target tumor. However, the amount of permeabilization is susceptible to the numerous uncertainties during treatment, such as patient-specific variations in the tissue, type of the tumor, and the resolution of imaging equipment. These uncertainties can reduce the extent of ablation in the tissue, thereby affecting the effectiveness of the treatment. Purpose: The aim of this work is to understand the effect of these treatment uncertainties on the treatment outcome for irreversible electroporation (IRE) in the case of colorectal liver metastasis (CRLM). Understanding the nature and extent of these effects can help us identify the influential treatment parameters and build better models for predicting the treatment outcome. Methods: This is an in silico study using a static computational model with a custom applicator design, spherical tissue, and tumor geometry. A nonlinear electrical conductivity, dependent on the local electric field, is considered. Morris analysis is used to identify the influential treatment parameters on the treatment outcome. Seven treatment parameters pertaining to the relative tumor location with respect to the applicator, the tumor growth pattern, and the electrical conductivity of tissue are analyzed. The treatment outcome is measured in terms of the relative tumor ablation with respect to the target ablation volume and total ablation volume. Results: The Morris analysis was performed with 800 model evaluations, sampled from the seven dimensional input parameter space. Electrical properties of the tissue, especially the electrical conductivity of the tumor before ablation, were found to be the most influential parameter for relative tumor ablation and total ablation volume. This parameter was found to be about 4-15 times more influential than the least influential parameter, depending on the tumor size. The tumor border configuration was identified as the least important parameter for treatment effectiveness. The most desired treatment outcome is obtained by a combination of high healthy liver conductivity and low tumor conductivity. This information can be used to tackle worst-case scenarios in treatment planning. Finally, when the safety margins used in the clinical applications are accounted for, the effects of uncertainties in the treatment parameters reduce drastically. Conclusions:The results of this work can be used to create an efficient surrogate estimator for uncertainty quantification in the treatmentThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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.

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