Irreversible electroporation (IRE) by high-strength electric pulses is a biomedical technique that has been effectively used for minimally invasive tumor therapy while maintaining the functionality ...of adjacent important tissues, such as blood vessels and nerves. In general, pulse delivery using needle electrodes can create a reversible electroporation region beyond both the ablation area and the vicinity of the needle electrodes, limiting enlargement of the ablation area. Electrochemical therapy (EChT) can also be used to ablate a tumor near electrodes by electrolysis using a direct field with a constant current or voltage (DC field). Recently, reversible electroporated cells have been shown to be susceptible to electrolysis at relatively low doses. Reversible electroporation can also be combined with electrolysis for tissue ablation. Therefore, the objective of this study is to use electrolysis to remove the reversible electroporation area and thereby enlarge the ablation area in potato slices
in vitro
using a pulsed field with a bias DC field (constant voltage). We call this protocol electrolytic irreversible electroporation (E-IRE). The area over which the electrolytic effect induced a pH change was also measured. The results show that decreasing the pulse frequency using IRE alone is found to enlarge the ablation area. The ablation area generated by E-IRE is significantly larger than that generated by using IRE or EChT alone. The ablation area generated by E-IRE at 1 Hz is 109.5% larger than that generated by IRE, showing that the reversible electroporation region is transformed into an ablation region by electrolysis. The area with a pH change produced by E-IRE is larger than that produced by EChT alone. Decreasing the pulse frequency in the E-IRE protocol can further enlarge the ablation area. The results of this study are a preliminary indication that the E-IRE protocol can effectively enlarge the ablation area and enhance the efficacy of traditional IRE for use in ablating large tumors.
The mechanism of changes in cell electroporation (EP) during the intervals of bipolar pulses is still unclear, and few studies have investigated the effect of the intervals at the molecular level. In ...this study, EP induced by bipolar pulses (BP) with different intervals was investigated using all-atom molecular dynamics simulations. Firstly, EP was formed during the positive pulses of 2 ns and 0.5 V nm
, then the effects of various intervals of 0, 1, 5, and 10 ns on EP evolution were investigated, and the dynamic changes of different degrees of EP induced by the following negative pulses of 2 ns and 0.5 V nm
were analyzed. The elimination effect of intervals was determined and it was related to the degrees of EP and the time of intervals. At the last moment of the intervals the phospholipid membrane was classified and quantitatively defined in three states according to the degrees of EP, namely, Resealing, Destabilizing and Retaining states. These states appeared due to the combined effect of both the positive pulse and the interval, and the states represent the degrees of EP which had different responses after applying the negative pulse. These results can improve our understanding of the fundamental mechanism of BP-induced EP.
Electrical breakdown in tissue electroporation Guenther, Enric; Klein, Nina; Mikus, Paul ...
Biochemical and biophysical research communications,
11/2015, Letnik:
467, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Electroporation, the permeabilization of the cell membrane by brief, high electric fields, has become an important technology in medicine for diverse application ranging from gene transfection to ...tissue ablation. There is ample anecdotal evidence that the clinical application of electroporation is often associated with loud sounds and extremely high currents that exceed the devices design limit after which the devices cease to function. The goal of this paper is to elucidate and quantify the biophysical and biochemical basis for this phenomenon. Using an experimental design that includes clinical data, a tissue phantom, sound, optical, ultrasound and MRI measurements, we show that the phenomenon is caused by electrical breakdown across ionized electrolysis produced gases near the electrodes. The breakdown occurs primarily near the cathode. Electrical breakdown during electroporation is a biophysical phenomenon of substantial importance to the outcome of clinical applications. It was ignored, until now.
•Electroporation is often associated with visible gas production and loud sounds.•This is caused by electrical breakdown across ionized electrolysis produced gases.•They are linked to the amount of electrolysis produced, voltage and pulse protocols.•These parameters should be respected when finding optimal treatment protocols.
Advances in in utero electroporation Kittock, Claire M.; Pilaz, Louis‐Jan
Developmental neurobiology (Hoboken, N.J.),
April-May 2023, 2023 Apr-May, 2023-04-00, 20230401, Letnik:
83, Številka:
3-4
Journal Article
Recenzirano
In utero electroporation (IUE) is a technique developed in the early 2000s to transfect the neurons and neural progenitors of embryonic brains, thus enabling continued development in utero and ...subsequent analyses of neural development. Early IUE experiments focused on ectopic expression of plasmid DNA to analyze parameters such as neuron morphology and migration. Recent advances made in other fields, such as CRISPR/CAS9 genome editing, have been incorporated into IUE techniques as they were developed. Here, we provide a general review of the mechanics and techniques involved in IUE and explore the breadth of approaches that can be used in conjunction with IUE to study cortical development in a rodent model, with a focus on the novel advances in IUE techniques. We also highlight a few cases that exemplify the potential of IUE to study a broad range of questions in neural development.
Electroporation-based therapies are powerful biotechnological tools for enhancing the delivery of exogeneous agents or killing tissue with pulsed electric fields (PEFs). Electrochemotherapy (ECT) and ...gene therapy based on gene electrotransfer (EGT) both use reversible electroporation to deliver chemotherapeutics or plasmid DNA into cells, respectively. In both ECT and EGT, the goal is to permeabilize the cell membrane while maintaining high cell viability in order to facilitate drug or gene transport into the cell cytoplasm and induce a therapeutic response. Irreversible electroporation (IRE) results in cell kill due to exposure to PEFs without drugs and is under clinical evaluation for treating otherwise unresectable tumors. These PEF therapies rely mainly on the electric field distributions and do not require changes in tissue temperature for their effectiveness. However, in immediate vicinity of the electrodes the treatment may results in cell kill due to thermal damage because of the inhomogeneous electric field distribution and high current density during the electroporation-based therapies. Therefore, the main objective of this numerical study is to evaluate the influence of pulse number and electrical conductivity in the predicted cell kill zone due to irreversible electroporation and thermal damage. Specifically, we simulated a typical IRE protocol that employs ninety 100-µs PEFs. Our results confirm that it is possible to achieve predominant cell kill due to electroporation if the PEF parameters are chosen carefully. However, if either the pulse number and/or the tissue conductivity are too high, there is also potential to achieve cell kill due to thermal damage in the immediate vicinity of the electrodes. Therefore, it is critical for physicians to be mindful of placement of electrodes with respect to critical tissue structures and treatment parameters in order to maintain the non-thermal benefits of electroporation and prevent unnecessary damage to surrounding healthy tissue, critical vascular structures, and/or adjacent organs.
Single-cell electroporation (SCEP) is a relatively new technique that has emerged in the last decade or so for single-cell studies. When a large enough electric field is applied to a single cell, ...transient nano-pores form in the cell membrane allowing molecules to be transported into and out of the cell. Unlike bulk electroporation, in which a homogenous electric field is applied to a suspension of cells, in SCEP an electric field is created locally near a single cell. Today, single-cell-level studies are at the frontier of biochemical research, and SCEP is a promising tool in such studies. In this review, we discuss pore formation based on theoretical and experimental approaches. Current SCEP techniques using microelectrodes, micropipettes, electrolyte-filled capillaries, and microfabricated devices are all thoroughly discussed for adherent and suspended cells. SCEP has been applied in in-vivo and in-vitro studies for delivery of cell-impermeant molecules such as drugs, DNA, and siRNA, and for morphological observations.
Background Ablation is increasingly used to treat primary and secondary liver cancer. Ablation near portal pedicles and hepatic veins is challenging. Irreversible electroporation (IRE) is a new ...ablation technique that does not rely on heat and, in animals, appears to be safe and effective when applied near hepatic veins and portal pedicles. This study evaluated the safety and short-term outcomes of IRE to ablate perivascular malignant liver tumors. Study Design A retrospective review of patients treated with IRE between January 1, 2011 and November 2, 2011 was performed. Patients were selected for IRE when resection or thermal ablation was not indicated due to tumor location. Treatment outcomes were classified by local, regional, and systemic recurrence and complications. Local failure was defined as abnormal enhancement at the periphery of an ablation defect on post-procedure contrast imaging. Results Twenty-eight patients had 65 tumors treated. Twenty-two patients (79%) were treated via an open approach and 6 (21%) were treated percutaneously. Median tumor size was 1 cm (range 0.5 to 5 cm). Twenty-five tumors were <1 cm from a major hepatic vein; 16 were <1 cm from a major portal pedicle. Complications included 1 intraoperative arrhythmia and 1 postoperative portal vein thrombosis. Overall morbidity was 3%. There were no treatment-associated mortalities. At median follow-up of 6 months, there was 1 tumor with persistent disease (1.9%) and 3 tumors recurred locally (5.7%). Conclusions This early analysis of IRE treatment of perivascular malignant hepatic tumors demonstrates safety for treating liver malignancies. Larger studies and longer follow-up are necessary to determine long-term efficacy.
Objectives
To evaluate longer‐term oncological and functional outcomes of focal irreversible electroporation (IRE) as primary treatment for localised clinically significant prostate cancer (csPCa) at ...a median follow‐up of 5 years (up to 10 years).
Patients and Methods
All patients that underwent focal IRE as primary treatment for localised PCa between February 2013 and August 2021 with a minimum 12 months of follow‐up were analysed. Follow‐up included 6‐month magnetic resonance imaging (MRI) and standardised transperineal saturation template ± targeted biopsies at 12 months, and further biopsies in the case of clinical suspicion on serial imaging and/or prostate‐specific antigen (PSA) levels. Failure‐free survival (FFS) was defined as no progression to radical treatment or nodal/distant disease. Local recurrence was defined as any International Society of Urological Pathology Grade of ≥2 on biopsy.
Results
A total of 229 patients were analysed with a median (interquartile range IQR) follow‐up of 60 (40–80) months. The median (IQR) age was 68 (64–74) years, the median (IQR) PSA level was 5.9 (4.1–8.2) ng/mL, and 86% harboured intermediate‐risk disease and 7% high‐risk disease. In all, 38 patients progressed to radical treatment (17%), at a median (IQR) of 35 (17–53) months after IRE. Kaplan–Meier FFS rates were 91% at 3 years, 84% at 5 years and 69% at 8 years. Metastasis‐free survival was 99.6% (228/229), PCa‐specific and overall survival were 100% (229/229). Residual csPCa was found in 24% (45/190) during follow‐up biopsy and MRI showed a complete ablation in 82% (186/226). Short‐term urinary continence was preserved (98%, three of 144 at baseline, 99%, one of 131 at 12 months) and erections sufficient for intercourse decreased by 13% compared to baseline (71% to 58%).
Conclusion
Longer‐term follow‐up confirms our earlier findings that focal IRE provides acceptable local and distant oncological control in selected men with less urinary and sexual toxicity than radical treatment. Long‐term follow‐up and external validation of these findings, is required to establish this new treatment paradigm as a valid treatment option.
Duodenal mucosa ablation (DMA) is a novel approach to treat diabetes, consisting of endoscopic ablation of dysfunctional diabetic duodenal mucosa, which, following the healing response, is replaced ...by normally functioning mucosa. Two techniques, duodenal mucosal resurfacing (DMR) and recellularization via electroporation therapy (ReCET), recently showed promise in type 2 diabetes mellitus (T2DM) patients.
Duodenal mucosa ablation (DMA) is a novel approach to treat diabetes, consisting of endoscopic ablation of dysfunctional diabetic duodenal mucosa, which, following the healing response, is replaced by normally functioning mucosa. Two techniques, duodenal mucosal resurfacing (DMR) and recellularization via electroporation therapy (ReCET), recently showed promise in type 2 diabetes mellitus (T2DM) patients.
When high-amplitude, short-duration pulsed electric fields are applied to cells and tissues, the permeability of the cell membranes and tissue is increased. This increase in permeability is currently ...explained by the temporary appearance of aqueous pores within the cell membrane, a phenomenon termed electroporation. During the past four decades, advances in fundamental and experimental electroporation research have allowed for the translation of electroporation-based technologies to the clinic. In this review, we describe the theory and current applications of electroporation in medicine and then discuss current challenges in electroporation research and barriers to a more extensive spread of these clinical applications.
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