Novel tetrapolar single-needle electrode for electrochemotherapy in bone cavities: Modeling, design and validation.

Electrochemotherapy is a cancer treatment in which local pulsed electric fields are delivered through electrodes. The effectiveness of the treatment depends on exposing the tumor to a threshold electric field. Electrode geometry plays an important role in the resulting electric field distribution, especially in hard-to-reach areas and deep-seated tumors. We designed and developed a novel tetrapolar single-needle electrode for proper treatment in bone cavities. In silico and in vitro experiments were performed to evaluate the electric field and electric current produced by the electrode. In addition, tomography images of a real case of nasal cavity tumor were segmented into a 3D simulation to evaluate the electrode performance in a bone cavity. The proposed electrode was validated and its operating range was set up to 650 V. In the nasal cavity tumor, we found that the electrode can produce a circular electric field of 3 mm with an electric current of 14.1 A at 500 V, which is compatible with electrochemotherapy standards and commercial equipment.

Biological dispersion in the time domain using finite element method software.

Biological tissue exhibits a strong dielectric dispersion from DC to GHz. Implementing biological dispersion in the time domain with commercial finite element method software could help improve engineering analysis of electrical transient phenomena. This article describes the steps required to implement time-domain biological dispersion with commercial finite element method software. The study begins with the presentation of a genetic algorithm to fit the experimental dispersion curve of Solanum tuberosum (potato tuber) to multipoles of first-order Debye dispersion. The results show that it is possible to represent the biological dispersion of S. tuberosum from 40 Hz to 10 MHz in a 4-pole Debye dispersion. Then, a set of auxiliary differential equations is used to transform the multipole Debye dispersion from the frequency domain to the time domain. The equations are implemented in the commercial software COMSOL Multiphysics. A comparison between the frequency and time domain simulations was used to validate the method. An analysis of the electric current with square-wave pulsed voltage was performed. We found that the computer implementation proposed in this work can describe the biological dispersion and predict the electric current.

Effects of pulse repetition rate in static electrochemotherapy models.

Electroporation alters cell membrane structure and tissue electrical properties by short and intense pulsed electric fields (PEF). Static mathematical models are often used to explain the change in electrical properties of tissues caused by electroporation. Electric pulse repetition rate may play an important role, as tissue dielectric dispersion, electroporation dynamics, and Joule heating may affect the electrical properties. In this work, we investigate the effects on the magnitude of the electric current when the repetition rate of the standard electrochemotherapy protocol is increased. Liver, oral mucosa, and muscle tissues were studied. Ex vivo animal experiments show that the magnitude of the electric current increases when the repetition rate is changed from 1 Hz to 5 kHz (10.8% for liver, 5.8% for oral mucosa, and 4.7% for muscle). Although a correction factor could reduce the error to less than 1%, dynamic models seem to be necessary to analyze different protocol signatures. Authors should be aware that static models and experimental results can only be compared if they use exactly the same PEF signature. The repetition rate is a key information to consider in the pretreatment computer study because the current at 1 Hz PEF differs from a 5 kHz PEF.

Electrochemotherapy treatment safety under parallel needle deflection.

Electrochemotherapy is a selective electrical-based cancer treatment. A thriving treatment depends on the local electric field generated by pairs of electrodes. Electrode damage as deflection can directly affect this treatment pillar, the distribution of the electric field. Mechanical deformations such as tip misshaping and needle deflection are reported with needle electrode reusing in veterinary electrochemotherapy. We performed in vitro and in silico experiments to evaluate potential problems with ESOPE type II electrode deflection and potential treatment pitfalls. We also investigated the extent to which the electric currents of the electroporation model can describe deflection failure by comparing in vitro with the in silico model of potato tuber (Solanum tuberosum). The in silico model was also performed with the tumor electroporation model, which is more conductive than the vegetal model. We do not recommend using deflected electrodes. We have found that a deflection of ± 2 mm is unsafe for treatment. Inward deflection can cause dangerous electrical current levels when treating a tumor and cannot be described with the in silico vegetal model. Outward deflection can cause blind spots in the electric field.

Adjuvant electrochemotherapy after debulking in canine bone osteosarcoma infiltration.

Osteosarcoma is a bone cancer considered rare to humans, but common in dogs. Dogs and humans share genetic homology and environmental risk factors. Improving the treatment of osteosarcoma in dogs could also be relevant to improve procedures in humans. Traditional treatments of osteosarcoma involve surgery and chemotherapy. Such treatments are commonly aggressive and not possible for many patients. Electrochemotherapy emerges as a minimally invasive, effective, and safe treatment alternative. Electrochemotherapy combines applications of high-intensity electric fields during short periods with anti-cancer drugs to improve its medicine cytotoxicity. Analyzing the electric field distribution, as well as electric current density, are essential to electrochemotherapy success. This paper brings the first case of a canine osteosarcoma treatment performed with bleomycin and electrochemotherapy. We performed in silico studies with finite element method software to observe the electric field distribution. In silico experiments help to verify possibilities and limitations of treating bone destruction and macro or micro tumor infiltrations around the primary tumor mass. Results show that both needle or plate electrodes are feasible to remove the tumor even with invasion into the bone. Plate electrodes perform well in treating micro infiltrations when associated with conductive gel and direct contact between electrode and bone (without soft tissues). Needle electrodes are effective in treating tumor infiltration on external cortical bone. Multiple applications are needed to cover all cranium layers with sufficient electric field intensity. Electrochemotherapy protocol with needle or plate electrodes does not present sufficient electric current density capable of affecting brain tissue, even in cases of bone destruction.