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Objectives: To assess laser–tissue interactions through ablation, coagulation, and carbonisation characteristics in a non‐perfused porcine kidney model between three pulsed lasers: holmium (Ho): yttrium‐aluminium‐garnet (YAG), thulium fiber laser (TFL), and pulsed thulium (p‐Tm):YAG. Materials and Methods: A 150‐W Ho:YAG, a 60‐W TFL, and a 100‐W p‐Tm:YAG lasers were compared. The laser settings that can be set identically between the three lasers and be clinically relevant for prostate laser enucleation were identified and used on fresh, unfrozen porcine kidneys. Laser incisions were performed using stripped laser fibers of 365 and 550 μm, set at distances of 0 and 1 mm from the tissue surface at a constant speed of 2 mm/s. Histological analysis evaluated shape, depth, width of the incision, axial coagulation depth, and presence of carbonisation. Results: Incision depths, widths, and coagulation zones were greater with Ho:YAG and p‐Tm:YAG lasers than TFL. Although no carbonisation was found with the Ho:YAG and p‐Tm:YAG lasers, it was common with TFL, especially at high frequencies. The shapes of the incisions and coagulation zones were more regular and homogeneous with the p‐Tm:YAG laser and TFL than with Ho:YAG laser. Regardless of the laser used, short pulse durations resulted in deeper incisions than long pulse durations. Concerning the distance, we found that to be effective, TFL had to be used in contact with the tissue. Finally, 365‐μm fibers resulted in deeper incisions, while 550‐μm fibers led to wider incisions and larger coagulation zones. Conclusion: Histological analysis revealed greater tissue penetration with the p‐Tm:YAG laser compared to the TFL, while remaining less than with Ho:YAG. Its coagulation properties seem interesting insofar as it provides homogeneous coagulation without carbonisation, while incisions remained uniform without tissue laceration. Thus, the p‐Tm:YAG laser appears to be an effective alternative to Ho:YAG and TFL lasers in prostate surgery. [ABSTRACT FROM AUTHOR]

In this paper, we report on the use of a purpose-built hybrid solid-state microwave and radiofrequency generator operating at frequencies of 2.45 GHz and/or 480 kHz for cancer ablation in various tissues. The hybrid generator was tested ex vivo on chicken breast and bovine liver and has demonstrated that the high accuracy of the power delivered to the sample can be achieved by controlling the emitted power versus the temperature profile of the treated sample. In particular, the hybrid generator incorporates control systems based on impedance or reflected power measurements that allow controlled ablation without causing unwanted carbonization and without including areas where tissue damage is not desired. The results of the ex vivo tests showed that radiofrequency ablation (RFA) could be effective for performing controlled ablations with minimally invasive probes, such as cardiac pathologies, small lesions, and tissues with particular composition, while microwave ablation (MWA) could be optimal for performing large ablations in highly vascularized tissues, such as liver cancer, where it is necessary to achieve higher temperatures.

[Objective] Electroporation has been widely used in biomedical applications, which is a typical medical--engineering cross-field. Currently, in the application of irreversible electroporation, the assessment of the ablation outcome in real time by medical imaging methods has become an issue. To solve this problem from the engineering field and create a teaching program for students in related majors, this study describes in detail how to build the electroporation platform and measure the ablation results and tissue impedance. The characteristics of the impedance variation are extracted by the equivalent circuit model. Finally, the correlation between the ablation outcome and the impedance change is discussed, which might be the new method to assess the ablation outcome in real-time. [Methods] This study investigated the tissue impedance changes and the ablation outcome induced by high-voltage pulsed electric fields. The pulsed voltage and current waveforms were recorded by an oscilloscope and used to analyze the electroporation process. The tissue impedance change induced by different pulse amplitudes was measured by an impedance analyzer, and the load characteristics were analyzed based on the impedance spectrum. To extract the characteristics of impedance change during treatment, the equivalent circuit model of tissue was proposed according to the features of the tissue structure. The measured impedance data were fitted to the circuit model to determine the value of every element in the circuit. The potato tube, which is the commonly used tissue model in irreversible electroporation, was used to detect the ablation outcome for different pulse parameters. The ablation outcome was quantified by the length and area of the ablated zone. [Results] The experimental results of the response current showed that: (1) At the first pulse, the increase in the current during pulse on time caused by electroporation could be easily identified. (2) As more pulses were applied, the current change during the pulse seemed to be saturated, indicating the saturation of electroporation. The measured impedance and the equivalent circuit model yielded the following results: (1) The impedance of the tissue started from the capacitive load, reflecting the polarization process between electrode and tissue. (2) As the frequency increased, the impedance could reflect the resistive characteristics of the extracellular fluid, the capacitive characteristics of the cell membrane, and the resistive characteristics of the intracellular fluid in sequence. (3) The circuit model could fit the impedance spectrum well, and the variation of the element value caused by the pulsed electric field could be explained by tissue electroporation. (4) The changing trends of the extracellular and cell membrane parameters were consistent with the ablation outcome, which had the potential to be used to assess the irreversible electroporation outcome in real-time. [Conclusions] By investigating the electrical and biomedical changes in the tissue after treatment by pulsed electric fields, the changes in the response current and impedance spectra are measured and correlated with the electroporation process. The equivalent circuit model can describe the tissue property well, and the changes in the extracellular resistance and cell membrane impedance are consistent with the ablation results. This study provides the potential electrical indicators to evaluate the ablation outcomes of irreversible electroporation in real-time. This teaching program helps students understand the connections between medicine and engineering, enhancing their skills in the application of theoretical knowledge in electrical engineering. [ABSTRACT FROM AUTHOR]

Low-temperature plasma ablation has been recently used for minimally invasive surgeries. However, more research is still needed on its generation process during tissue ablation and the underlying mechanism of tissue thermal damage. In this paper, high-speed camera footage, voltage–current signal collection, temperature analysis, and histological analysis were used to investigate the dynamic process of plasma tissue ablation and its thermal effect of dual-needle electrodes immersed in normal saline, which were driven by a high-frequency DC power supply with an output voltage ranging from 220 V to 320 V and a squire wave of 100 kHz. Microbubbles occurred around the ground electrode and merged to form a vapor layer that could completely cover the ground electrode. Plasma capable of ablating tissue would occur in the vapor layer between the ground electrode and tissue. The effect of electrical parameters on plasma generation and its thermal effect are analyzed by statistical results. The experimental results indicated that the voltage applied to the electrodes significantly influenced both the generation and stability of plasma, as well as the heat generation and tissue damage around the electrodes. Furthermore, under the same voltage, the existence of biological tissue promotes the formation of a vapor layer around the electrode, thereby facilitating the generation and stability of plasma. Notably, the temperature rise around the ground electrode is much higher than that around the powered electrode. These results have direct application to the design of plasma tissue ablation systems, which could achieve tissue ablation effects with minimal thermal damage. [ABSTRACT FROM AUTHOR]

In this paper, we report on the use of a purpose-built hybrid solid-state microwave and radiofrequency generator operating at frequencies of 2.45 GHz and/or 480 kHz for cancer ablation in various tissues. The hybrid generator was tested ex vivo on chicken breast and bovine liver and has demonstrated that the high accuracy of the power delivered to the sample can be achieved by controlling the emitted power versus the temperature profile of the treated sample. In particular, the hybrid generator incorporates control systems based on impedance or reflected power measurements that allow controlled ablation without causing unwanted carbonization and without including areas where tissue damage is not desired. The results of the ex vivo tests showed that radiofrequency ablation (RFA) could be effective for performing controlled ablations with minimally invasive probes, such as cardiac pathologies, small lesions, and tissues with particular composition, while microwave ablation (MWA) could be optimal for performing large ablations in highly vascularized tissues, such as liver cancer, where it is necessary to achieve higher temperatures. [ABSTRACT FROM AUTHOR]

Background and objective:: Globally, irreversible electroporation (IRE) emerges as a promising technique for tissue ablation as it overcomes the limitations of the benchmark techniques. However, achieving the desired and safe ablation volume of tissue pivots on multiple factors, such as pulse profile, shape, and number of electrodes, besides the IRE treatment parameters, like pulse type, field strength, number of pulses, pulse length, and frequency. This work aims to develop a 3D computation platform that predicts the ablation volume using the IRE procedure and provides insights such as electric field, temperature and its corresponding cell survival regions. Thereby, such a platform aids in selecting optimized treatment parameters to avoid thermal damage. In addition, the developed IRE model estimates the relationship between the pulse protocol and different electrode geometries, number of electrodes, and electrode configurations. Methods:: The computational model for IRE is developed with Laplace’s equation and Penn’s bio-heat equation for the electric potential and temperature profiles, respectively, and the Finite Difference method is considered for the numerical solution. The statistical Fermi equation-based Peleg model has been adapted to estimate the ablation volume as a function of the magnitude of the electric field and other electric field parameters. Results:: The tissue ablation platform allows computation and visualization of ablation volume estimation using the IRE technique with a pair of plate-type and multiple pairs of needle-type electrodes. IRE treatment with different combinations of electric pulse parameters, i.e., pulse length, voltage, and number of pulses, causes different levels of temperature rise. By adapting our platform, one can avoid thermal damage in the IRE treatment with the right combination of pulse parameters. For instance, one can apply a maximum of 10 pulses restricting temperature within 50°C in the IRE treatment of cervical tissue with a couple of pairs of needle-type electrodes and 100μs electric pulses of 3000V. Conclusion:: The proposed IRE model aids in treatment planning for tissue ablation with 3D visual outputs through the platform’s user interface for better clinical insights, including interpretability, data resolution, and computational cost.

Our objective was to develop a technique for performing irreversible electroporation (IRE) of esophageal tumors while mitigating thermal damage to the healthy lumen wall. We investigated noncontact IRE using a wet electrode approach for tumor ablation in a human esophagus with finite element models for electric field distribution, joule heating, thermal flux, and metabolic heat generation. Simulation results indicated the feasibility of tumor ablation in the esophagus using an catheter mounted electrode immersed in diluted saline. The ablation size was clinically relevant, with substantially lesser thermal damage to the healthy esophageal wall when compared to IRE performed by placing a monopolar electrode directly into the tumor. Additional simulations were used to estimate ablation size and penetration during noncontact wet-electrode IRE (wIRE) in the healthy swine esophagus. A novel catheter electrode was manufactured and wIRE evaluated in seven pigs. wIRE was performed by securing the device in the esophagus and using diluted saline to isolate the electrode from the esophageal wall while providing electric contact. Computed tomography and fluoroscopy were performed post-treatment to document acute lumen patency. Animals were sacrificed within four hours following treatment for histologic analysis of the treated esophagus. The procedure was safely completed in all animals; post-treatment imaging revealed intact esophageal lumen. The ablations were visually distinct on gross pathology, demonstrating full thickness, circumferential regions of cell death (3.52 ± 0.89 mm depth). Acute histologic changes were not evident in nerves or extracellular matrix architecture within the treatment site. Catheter directed noncontact IRE is feasible for performing penetrative ablations in the esophagus while avoiding thermal damage. [ABSTRACT FROM AUTHOR]

Microwave (MW) ablation is becoming a routine technology in the interventional radiology field. A new approach combining MW ablation and chemical ablation is developed in this paper. The rationale for the development of this Microwave-Assisted Chemical Ablation (MA-CA) technology was to improve the utility of thermal ablation as a minimally invasive treatment for cancer. The experimental conditions for ex vivo bovine liver samples were: A—100 W (120 s) with no addition of ethanol; B—100 W (30 s), wait (60 s) (no power), and 100 W (90 s) with no addition of ethanol; C—100 W (30 s), wait (60 s), 100 W (30 s), and 100 W (60 s) with the addition of 5 mL ethanol; and D—100 W (30 s), wait (60 s), 100 W (30 s), 0 W (30 s) with the addition of 2.5 mL ethanol, and 100 W (60 s) with the addition of 5 mL ethanol (12,000 Joules Total). The results showed that with the use of ethanol, the ablation zone was enlarged and revealed improved sphericity. This novel combination has greater advantages than either technology individually. The objective is to increase the precision and efficiency of MW ablation and to broaden the range of tissues and pathologies that can be treated using this new approach, and to validate the benefits that arise from combining the advantages of MW and chemical ablation in a relevant setting. [ABSTRACT FROM AUTHOR]

This article describes a sapphire cryoprobe as a promising solution to the significant problem of modern cryosurgery that is the monitoring of tissue freezing. This probe consists of a sapphire rod manufactured by the edge‐defined film‐fed growth technique from Al2O3 melt and optical fibers accommodated inside the rod and connected to the source and the detector. The probe's design enables detection of spatially resolved diffuse reflected intensities of tissue optical response, which are used for the estimation of tissue freezing depth. The current type of the 12.5‐mm diameter sapphire probe cooled down by the liquid nitrogen assumes a superficial cryoablation. The experimental test made by using a gelatin‐intralipid tissue phantom shows the feasibility of such concept, revealing the capabilities of monitoring the freezing depth up to 10 mm by the particular instrumentation realization of the probe. This justifies a potential of sapphire‐based instruments aided by optical diagnosis in modern cryosurgery. [ABSTRACT FROM AUTHOR]

Irreversible electroporation (IRE) is a non-thermal tissue ablation technique that utilizes high-voltage pulses between electrode pairs to destroy tissue. Numerical models are essential for predicting treatment outcomes and aiding in treatment planning. This paper studies a nonlinear conductivity model (NC) and a multiparametric nonlinear conductivity model (MPNC) to investigate overlapping electroporation treatments using a three-needle electrode configuration. The NC model accounts for the effects of the electric field and temperature on tissue conductivity during multiple pulsed electric field applications. The MPNC model incorporates the influence of pulse number, alongside electric field and temperature, on tissue conductivity. Results indicate that in the MPNC model, tissue conductivity is significantly higher in regions where the electric field intensity is below the threshold for irreversible electroporation, with the maximum difference reaching 0. 4 S/m. In contrast, tissue conductivity is slightly lower in regions where the electric field intensity exceeds the IRE threshold. Additionally, the MPNC model predicts a smaller area of irreversible electroporation and a larger area of reversible electroporation, with these differences becoming more pronounced as the distance between electrode needles increases. These findings underscore the importance of considering pulse number effects in numerical models to enhance the accuracy of treatment planning for irreversible electroporation-based therapies. [ABSTRACT FROM AUTHOR]

Electroporation is used to increase the permeability of the cell membrane through high-voltage electric pulses. Nowadays, it is widely used in different areas, such as medicine, biotechnology, and the food industry. Electroporation induces the formation of hydrophilic pores in the lipid bilayer of cell membranes, to allow the entry or exit of molecules that cannot otherwise cross this hydrophobic barrier. In this article, we critically review the basic principles of electroporation, along with the advantages and drawbacks of this method. We discuss the effects of electroporation on the key components of biological membranes, as well as the main applications of this procedure in medicine, such as electrochemotherapy, gene electrotransfer, and tissue ablation. Finally, we define the most relevant challenges of this promising area of research.

We present the porcine skin ablation using a mid-infrared high-repetition-rate picosecond pulse burst laser. A burst-mode pulse with a repetition rate of 16.32 MHz was generated from a home-built difference frequency generation (DFG) system operating at 3 μm. Within each burst, there were 16 equally spaced 8.5 ps sub-pulses at an intra-burst repetition rate of ∼3.3 GHz. To study the laser-tissue interaction, laser powers of 1 to 2 W, and scanning times from 1 to 10 with spot size of ∼50 μm were applied to irradiate the fresh porcine skin. The results demonstrate that the burst-mode pulse with modest peak power density of MW/cm2 is efficient for tissue ablation. The optimized ablation depth increased with the average power and scanning times, reaching a maximal incision depth of 150 μm. Thanks to the high repetition rate of intra-burst pulse and high absorption of radiation, the ablation width and thermal effect width kept within 50 μm and 25 μm in all control groups. It is believed that as the first demonstration, such mid-infrared burst-mode laser radiation with modest power intensity is of great potential to realize micron penetration depth and low thermal effect in high-precision surgery applications.

Objective: Contact irreversible electroporation (IRE) is a method for ablating cells by applying electric pulses via surface electrodes in contact with a target tissue. To facilitate the application of the contact IRE to superficial lesion treatment, this study further extended the ablation depth, which had been limited to a 400-μm depth in our previous study, by using concentric electrodes. Methods: A prototype device of concentric electrodes was manufactured using a Teflon-coated copper wire inserted in a copper tube. The ablation area was experimentally determined using a tissue phantom comprising 3D cultured fibroblasts and compared with the electric field distribution obtained using numerical analyses. Results: Experiments showed that cells 540 μm from the surface of the tissue phantom were necrotized by the application of 150 pulses at 100 V. The outline of the ablation area agreed well with the contour line of 0.4 kV/cm acquired by the analyses. The ablation depth predicted for the concentric electrode using this critical electric field was 1.4 times deeper than that for the parallel electrode. For the actual application of treatment, a multiple-electrode device that bundles several pairs of concentric electrodes was developed, and confirmed that to be effective for treating wide areas with a single treatment. Conclusion: The electric field estimated by the analyses with the experimentally determined threshold confirmed that concentric electrodes could attain a deeper ablation than parallel electrodes. Significance: Using the concentric electrodes, we were able to localize ablation to specific target cells with much less damage to neighboring cells. [ABSTRACT FROM AUTHOR]

Microwave (MW) ablation is becoming a routine technology in the interventional radiology field. A new approach combining MW ablation and chemical ablation is developed in this paper. The rationale for the development of this Microwave-Assisted Chemical Ablation (MA-CA) technology was to improve the utility of thermal ablation as a minimally invasive treatment for cancer. The experimental conditions for ex vivo bovine liver samples were: A—100 W (120 s) with no addition of ethanol; B—100 W (30 s), wait (60 s) (no power), and 100 W (90 s) with no addition of ethanol; C—100 W (30 s), wait (60 s), 100 W (30 s), and 100 W (60 s) with the addition of 5 mL ethanol; and D—100 W (30 s), wait (60 s), 100 W (30 s), 0 W (30 s) with the addition of 2.5 mL ethanol, and 100 W (60 s) with the addition of 5 mL ethanol (12,000 Joules Total). The results showed that with the use of ethanol, the ablation zone was enlarged and revealed improved sphericity. This novel combination has greater advantages than either technology individually. The objective is to increase the precision and efficiency of MW ablation and to broaden the range of tissues and pathologies that can be treated using this new approach, and to validate the benefits that arise from combining the advantages of MW and chemical ablation in a relevant setting.

BackgroundElectrolytic ablation and electroporation based ablation are minimally invasive, non-thermal surgical technologies that employ electrical currents and electric fields to ablate undesirable cells in a volume of tissue. In this study, we explore the attributes of a new tissue ablation technology that simultaneously delivers a synergistic combination of electroporation and electrolysis (E2).MethodA new device that delivers a controlled dose of electroporation field and electrolysis currents in the form of a single exponential decay waveform (EDW) was applied to the pig liver, and the effect of various parameters on the extent of tissue ablation was examined with histology.ResultsHistological analysis shows that E2 delivered as EDW can produce tissue ablation in volumes of clinical significance, using electrical and temporal parameters which, if used in electroporation or electrolysis separately, cannot ablate the tissue.DiscussionThe E2 combination has advantages over the three basic technologies of non-thermal ablation: electrolytic ablation, electrochemical ablation (reversible electroporation with injection of drugs) and irreversible electroporation. E2 ablates clinically relevant volumes of tissue in a shorter period of time than electrolysis and electroporation, without the need to inject drugs as in reversible electroporation or use paralyzing anesthesia as in irreversible electroporation.

Nonthermal irreversible electroporation is a new tissue ablation technique that consists of applying pulsed electric fields across cells to induce cell death by creating permanent defects in the cell membrane. Nonthermal irreversible electroporation is of interest because it allows treatment near sensitive tissue structures such as blood vessels and nerves. Two recent articles report that electrolytic reaction products at electrodes can be combined with electroporation pulses to augment and optimize tissue ablation. Those articles triggered a concern that the results of earlier studies on nonthermal irreversible electroporation may have been tainted by unaccounted for electrolytic effects. The goal of this study was to reexamine previous studies on nonthermal irreversible electroporation in the context of these articles. The study shows that the results from some of the earlier studies on nonthermal irreversible electroporation were affected by unaccounted for electrolysis, in particular the research with cells in cuvettes. It also shows that tissue ablation ascribed in the past to irreversible electroporation is actually caused by at least 3 different cytotoxic effects: irreversible electroporation without electrolysis, irreversible electroporation combined with electrolysis, and reversible electroporation combined with electrolysis. These different mechanisms may affect cell and tissue ablation in different ways, and the effects may depend on various clinical parameters such as the polarity of the electrodes, the charge delivered (voltage, number, and length of pulses), and the distance of the target tissue from the electrodes. Current clinical protocols employ ever-increasing numbers of electroporation pulses to values that are now an order of magnitude larger than those used in our first fundamental nonthermal irreversible electroporation studies in tissues. The different mechanisms of cell death, and the effect of the clinical parameters on the mechanisms may explain discrepancies between results of different clinical studies and should be taken into consideration in the design of optimal electroporation ablation protocols.

Objective: To assess the fiber–tissue interaction through ablation, coagulation, and carbonization characteristics of the Ho:YAG laser and super pulsed thulium fiber laser (TFL) in a nonperfused porcine kidney model. To assess the degradation of laser fibers during soft tissue treatment. Methods: A 50 W TFL generator was compared with a 120 W Ho:YAG laser. The laser settings that can be set identically between the two lasers (pulse energy and frequency), and clinically relevant for prostate laser enucleation, were identified and used for tissue incisions on fresh nonfrozen porcine kidneys. For each parameter, the short, medium, and long pulse durations for the Ho:YAG generator and the different peak powers 150, 250, and 500 W for the TFL generator were also tested. Laser incisions were performed with 550 μm stripped laser fiber fixed on a robotic arm at a distance of 0.1 mm with the tissue surface and at a constant speed of 10 mm/s. Histologic analysis was then performed, evaluating incision shape, incision depth and width, axial coagulation depth, and presence of carbonization. Degradation of the laser fiber was defined as reduction of laser fiber tip length after laser activation. Results: Incision depths and areas of coagulation were greater with the Ho:YAG laser than those with the TFL. Although no carbonization zone was found with the Ho:YAG laser, this was constant with the TFL. Although a fiber tip degradation was constantly observed with Ho:YAG laser, except in the case of a long pulse duration and low pulse energy (0.2 J), this was not the case with TFL. Conclusion: TFL appears to be an efficient alternative to Ho:YAG laser for soft tissue surgery. The histologic analysis found greater tissue penetration with the Ho:YAG laser and different coagulation properties between the two lasers. These results need to be investigated in vivo to assess the clinical impact of these differences and find the optimal settings for laser prostate enucleation. [ABSTRACT FROM AUTHOR]

Tissue ablation techniques have emerged as a critical component of modern medical practice and biomedical research, offering versatile solutions for treating various diseases and disorders. Percutaneous ablation is minimally invasive and offers numerous advantages over traditional surgery, such as shorter recovery times, reduced hospital stays, and decreased healthcare costs. Intra-procedural imaging during ablation also allows precise visualization of the treated tissue while minimizing injury to the surrounding normal tissues, reducing the risk of complications. Here, the mechanisms of tissue ablation and innovative energy delivery systems are explored, highlighting recent advancements that have reshaped the landscape of clinical practice. Current clinical challenges related to tissue ablation are also discussed, underlining unmet clinical needs for more advanced material-based approaches to improve the delivery of energy and pharmacology-based therapeutics., (© 2024 Wiley‐VCH GmbH.)

Nitroreductases, enzymes found mostly in bacteria and also in few eukaryotes, use nicotinamide adenine dinucleotide (NADH) or nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor for their activity and metabolize an enormous list of a diverse nitro group‐containing compounds. Nitroreductases that are capable of metabolizing nitroaromatic and nitro heterocyclic compounds have drawn great attention in recent years owing to their biotechnological, biomedical, environmental, and human impact. These enzymes attracted medicinal chemists and pharmacologists because of their prodrug selectivity for activation/reduction of nitro compounds that wipe out pathogens/cancer cells, leaving the host/normal cells unharmed. It is applied in diverse fields of study like prodrug activation in treating cancer and leishmaniasis, designing fluorescent probes for hypoxia detection, cell imaging, ablation of specific cell types, biodegradation of nitro‐pollutants, and interpretation of mutagenicity of nitro compounds. Keeping in view the immense prospects of these enzymes and a large number of research contributions in this area, the present review encompasses the enzymatic reaction mechanism, their role in antibiotic resistance, hypoxia sensing, cell imaging, cancer therapy, reduction of recalcitrant nitro chemicals, enzyme variants, and their specificity to substrates, reaction products, and their applications. [ABSTRACT FROM AUTHOR]

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 used to increase the permeability of the cell membrane through high-voltage electric pulses. Nowadays, it is widely used in different areas, such as medicine, biotechnology, and the food industry. Electroporation induces the formation of hydrophilic pores in the lipid bilayer of cell membranes, to allow the entry or exit of molecules that cannot otherwise cross this hydrophobic barrier. In this article, we critically review the basic principles of electroporation, along with the advantages and drawbacks of this method. We discuss the effects of electroporation on the key components of biological membranes, as well as the main applications of this procedure in medicine, such as electrochemotherapy, gene electrotransfer, and tissue ablation. Finally, we define the most relevant challenges of this promising area of research. [ABSTRACT FROM AUTHOR]

A forward-looking miniature histotripsy transducer has been developed that incorporates an acoustic lens and dual-frequency stacked transducers. An acoustic lens is used to increase the peak negative pressure through focal gain and the dual-frequency transducers are designed to increase peak negative pressure by summing the pressure generated by each transducer individually. Four lens designs, each with an ${f}$ -number of approximately 1, were evaluated in a PZT5A composite transducer. The finite-element model (FEM) predicted axial beamwidths of 1.61, 2.40, 2.84, and 2.36 mm for the resin conventional, resin Fresnel, silicone conventional, and silicone Fresnel lenses, respectively; the measured axial beamwidths were 1.30, 2.28, 2.71, and 2.11 mm, respectively. Radial beamwidths from the model were between 0.32 and 0.35 mm, while measurements agreed to within 0.2 mm. The measured peak negative was 0.150, 0.124, 0.160, and 0.160 MPa/V for the resin conventional, resin Fresnel, silicone conventional, and silicone Fresnel lenses, respectively. For the dual-frequency device, the 5-MHz (therapy) transducer had a measured peak negative pressure of 0.136 MPa/V for the PZT5A composite and 0.163 MPa/V for the PMN-PT composite. The 1.2-MHz (pump) transducer had a measured peak negative pressure of 0.028 MPa/V. The pump transducer significantly lowered the cavitation threshold of the therapy transducer. The dual-frequency device was tested on an ex vivo rat brain, ablating tissue at up to 4-mm depth, with lesion sizes as small as $500~\mu \text{m}$. [ABSTRACT FROM AUTHOR]

A 34-mm aperture transducer was designed and tested for proof of concept to ablate tissues using an endocavity histotripsy device. Several materials and two drivers were modeled and tested to determine an effective piezoelectric–matching layer combination and driver design. The resulting transducer was fabricated using 1.5 MHz porous PZT and PerFORM 3-D printed acoustic lenses and was driven with a multicycle class-D amplifier. The lower frequency, compared to previously developed small form factor histotripsy transducers, was selected to allow for more efficient volume ablation of tissue. The transducer was characterized and tested by measuring pressure field maps in the axial and lateral planes and pressure output as a function of driving voltage. The axial and lateral full-width-half-maximums of the focus were found to be 6.1 and 1.1 mm, respectively. The transducer was estimated to generate 34.5-MPa peak negative focal pressure with a peak-to-peak driving voltage of 1345 V. Performance testing was done by ablating volumes of bovine liver tissues (${n} = {3}$). The transducer was found to be capable of ablating tissues at its full working distance of 17 mm. [ABSTRACT FROM AUTHOR]

Introduction: There are limited data regarding the effect of thulium laser (Tm:YAG) and holmium laser (Ho:YAG) on upper urinary tract. The aim of this study was to compare soft tissue effects of these two lasers at various settings, with a focus on incision depth (ID) and coagulation area (CA). Materials and Methods: An ex vivo experimental study was performed in a porcine model. The kidneys were dissected to expose the upper urinary tract and the block samples containing urothelium and renal parenchyma were prepared. The laser fiber, fixed on a robotic arm, perpendicular to the target tissue was used with a 100 W Ho:YAG and a 200 W Tm:YAG. Incisions were made with the laser tip in contact with the urothelium and in continuous movement at a constant speed of 2 mm/s over a length of 1.5 cm. Total energy varied from 5 to 30 W. Incision shape was classified as follows: saccular, triangular, tubular, and irregular. ID, vaporization area (VA), CA, and total laser area (TLA = VA + CA) were evaluated. Statistical analysis was performed using the SPSS V23 package, p-values <0.05 were considered statistically significant. Results: A total of 216 experiments were performed. Incision shapes were saccular (46%), triangular (38%), and irregular (16%) with the Ho:YAG, while they were tubular (89%) and irregular (11%) with the Tm:YAG. ID was significantly deeper with the Ho:YAG (p = 0.024), while CA and TLA were larger with the Tm:YAG (p < 0.001 and p < 0.005). Conclusion: ID was deeper with Ho:YAG, whereas CA and TLA were larger with the Tm:YAG. Considering surgical principles for endoscopic ablation of upper tract urothelial carcinoma, these results suggest that Tm:YAG may have a lower risk profile (less depth of incision) while also being more efficient at tissue destruction. Future in vivo studies are necessary to corroborate these findings. [ABSTRACT FROM AUTHOR]

"Surgical smoke" is an airborne by-product of electrosurgery comprised of vapour and suspended particles. Although concerns exist that exposure may be harmful, there is a poor understanding of the smoke in terms of particle size, morphology, composition and biological viability. Notably, it is not known how the biological tissue source and cutting method influence the smoke. The objective of this study was to develop a collection method for airborne by-product from surgical cutting. This would enable comprehensive analyses of the particulate burden, composition and biological viability. The method was applied to compare the electrosurgical smoke generated (in the absence of any evacuation mechanism) with the aerosolized/airborne by-products generated by ultrasonic and high-speed cutting, from bone and liver tissue cutting. We report a wide range of particle sizes (0.93–806.31 μm for bone, 0.05–1040.43 μm for liver) with 50% of the particles being <2.72 μm (~PM2.5) and 90% being <10 μm (PM10). EDX and biochemical analysis reveal components of biological cells and cellular metabolic activity in particulate from liver tissue cut by electrosurgery and ultrasonic cutting. We show for the first time however that bone saws and ultrasonic cutting do not liberate viable cells from bone. [ABSTRACT FROM AUTHOR]

In the technology driven era, robot assisted surgery is gradually emerging as a revolutionized surgical procedure over traditional laparoscopic method. Despite the concerns about robotic surgery for minimally invasive surgical procedures, robotized surgical arms have been used in many hospitals. Certain surgical procedures require removal of a segment of an organ or body part like excision biopsy, linear thin layer of soft tissue, triangular mass, and tangential excision in burn management, where shaving-off at an angle of the tissue layer to be removed. For such minimally invasive procedures, we have designed a surgical arm governed by a rotary flexible joint. The surgical arm has a medical grade scalpel in its one end and the other end is connected to a D.C. servo motor. The motion of the surgical arm is controlled by the newly designed non-integer order controller. We have experimentally demonstrated the functioning of the surgical arm by ablating the tissue in-vitro. Our surgical robotic arm is cost effective, high precision and free from potential human errors. [ABSTRACT FROM AUTHOR]

In this article, we proposed a laser hot needle for liver tissue tract ablation. The proposed laser hot needle is powered by a 4500-nm-diode laser incorporated with a closed-loop control system that comprises of a uniform fiber Bragg grating (FBG) temperature sensor and a computer. Based on the real-time feedback input from the FBG temperature sensor, the laser power is regulated by a proportional–integral–derivative (PID) control system to control the needle temperature. In the characterization test, a chirped grating-based distributed temperature sensor is employed for measuring the tissue temperature profile in the ex vivo bovine liver tissue during the ablation. A histological test is conducted to study the impact of tract ablation to the cellular structures of treated tissue and tissue coagulation. In a tract ablation test, a ~50-mm × ~ 6-mm (length × width) thermal denaturation zone has been created on ex vivo bovine liver tissue with the laser hot needle at 150 °C. [ABSTRACT FROM AUTHOR]

Radiofrequency ablation (RFA) is a non-invasive image-guided procedure where tumors are heated in the body with electrical current. RFA procedures are commonly indicated for patients with limited local disease or who are not surgical candidates. Current methods of RFA use multiple cords and wires that ergonomically complicate the procedure and present the risk of cutting or shorting the circuit if they are damaged. A wireless RFA technique based on electromagnetic induction is presented in this paper. The transmitting and receiving coils were coupled to resonate at the same frequency to ensure the highest power output. The receiving coil was connected to two insulated electrodes on a catheter, which allowed the current to flow to the targeted tissue. The prototype system was tested with ex-vivo bovine tissue, which has similar thermal and electrical properties to human tissue. The setup can monitor the received power, efficiency, temperature, and ablation zone during ablation procedures. The maximum received power was 15 W, and the average maximum efficiency was 63.27%. The novel system was also able to ablate up to a 2 cm ablation zone in non-perfused tissue. This proof of concept for performing RFA wirelessly with electromagnetic induction may merit further optimization. [ABSTRACT FROM AUTHOR]

Electroporation is a bioelectric phenomenon used to deliver target molecules into cells in vitro and irreversible electroporation (IRE) is an emerging cancer therapy used to treat inoperable tumors in situ. These phenomena are generally considered to be non-thermal in nature. In this study, a 3D tumor model was used to investigate the correlation between temperature and the effectiveness of standard clinical IRE and high frequency (H-FIRE) protocols. It was found for human glioblastoma cells that in the range of 2 to 37 °C the H-FIRE lethal electric field threshold value, which describes the minimum electric field to cause cell death, is highly dependent on temperature. Increasing the initial temperature from 2 to 37 °C resulted in a significant decrease in lethal electric field threshold from 1168 to 507 V/cm and a 139% increase in ablation size for H-FIRE burst treatments. Standard clinical protocol IRE treatments resulted in a decrease in lethal threshold from 485 to 453 V/cm and a 7% increase in ablation size over the same temperature range. Similar results were found for pancreatic cancer cells which indicate that tissue temperature may be a significant factor affecting H-FIRE ablation size and treatment planning in vivo while lower temperatures may be useful in maintaining cell viability for transfection applications. [ABSTRACT FROM AUTHOR]

Argon plasma coagulation (APC) is used widely and effectively in therapeutic gastrointestinal endoscopy, mainly to achieve both haemostasis and tissue ablation. The main advantages of APC treatment are its ease of application, cost effectiveness, improved safety and reduced time for application. This review gives an insight into the safe and effective use of APC in the gastrointestinal tract with flexible endoscopy. It discusses the technical aspects of the APC generator, the different types of APC probes tailored to the indication and the target tissue. It also discusses patient preparation, including the optimal pre- and post-APC care instructions. [ABSTRACT FROM AUTHOR]

In this article, we proposed a laser hot needle for liver tissue tract ablation. The proposed laser hot needle is powered by a 4500-nm-diode laser incorporated with a closed-loop control system that comprises of a uniform fiber Bragg grating (FBG) temperature sensor and a computer. Based on the real-time feedback input from the FBG temperature sensor, the laser power is regulated by a proportional–integral–derivative (PID) control system to control the needle temperature. In the characterization test, a chirped grating-based distributed temperature sensor is employed for measuring the tissue temperature profile in the ex vivo bovine liver tissue during the ablation. A histological test is conducted to study the impact of tract ablation to the cellular structures of treated tissue and tissue coagulation. In a tract ablation test, a ~50-mm $\times \sim 6$ -mm (length $\times $ width) thermal denaturation zone has been created on ex vivo bovine liver tissue with the laser hot needle at 150 °C. [ABSTRACT FROM AUTHOR]

Ultrafast laser ablation may provide a treatment for vocal fold (VF) scarring. Optical properties of VFs must be known prior to clinical implementation to select appropriate laser surgery conditions. We present scattering lengths of epithelium ls,ep, superficial lamina propria ls;SLP, and ablation thresholds Fth of human and canine VF tissues. Our experimental approach involves an image-guided, laser-ablation-based method that allows for simultaneous determination of ls and Fth in these multilayered tissues. Studying eight canine samples, we found ls;ep ¼ 75.3± 5.7 μm, ls;SLP ¼ 26.1±1.2 μm, Fth;ep ¼ 1.58±0.06 J/cm2, and Fth;SLP ¼ 1.55±0.17 J/cm2. Studying five human samples, we found ls;ep ¼ 42.8±3.3 μm and Fth;ep ¼ 1.66±0.10 J/cm2. We studied the effects of cumulative pulse overlap on ablation threshold and found no significant variations beyond 12 overlapping pulses. Interestingly, our studies about the effect of sample storage on the scattering properties of porcine VF show a 60% increase in ls;ep for fresh porcine VF when compared to the same sample stored in isotonic solution. These results provide guidelines for clinical implementation by enabling selection of optimal laser surgery parameters for subsurface ablation of VF tissues. [ABSTRACT FROM AUTHOR]

Abstract This study examined the temporal physiological and molecular events following the treatment of the liver with a tissue ablation modality that combined electroporation with electrolysis (E2). Rat liver was treated with an E2 waveform and the tissue examined, 1 h, 3 h, 6 h and 24 h with: H&E, Masson Trichrome, TUNEL stains and Western blot. H&E and TUNEL stains have shown that cell death began to be evident 3 h and hepatocyte regeneration was seen 24 h after treatment. H&E and Masson trichrome have shown that the extracellular matrix and the large lumens, appeared intact after E2. Western blot has shown the following molecular events after E2: cleaved caspase 3–downgraded at 1 h, upgraded at 24 h (apoptosis); cleaved Caspase 1 and cleaved GSDMD–upgraded at 6 h (pyroptosis), RIP3–upgraded at 1 h, MLKL–upgraded at 3 h (necroptosis). The mechanism of cell death was possible initiated by necroptosis pathway. Pyroptosis pathway was also activated. The observation that cell death from E2 was by programed necrosis and the details on the temporal molecular pathways, may have value for the recent attempt to combine electroporation mediated ablation with immunological treatment, by demonstrating that the cell death from E2 involves an inflammatory response and by providing data that could be used to design the optimal timing for the injection of immunological adjuvants. Highlights • A tissue ablation modality that combines electrolysis and electroporation (E2). • Necroptosis pathways lead the molecular process of cell death. • No evidence of cell death by apoptosis from electroporation and electrolysis. • Extracellular matrix appears intact after electroporation and electrolysis. • Hepatocytes regeneration was seen 24 h after treatment. [ABSTRACT FROM AUTHOR]

Time-resolved measurement of the stress transients generated by pulsed infrared irradiation and ablation of tissue has demonstrated that these processes are governed primarily by photothermal processes. For ablation of porcine dermis at 2.79 micrometer (Q-sw Er:YSGG) and 10.6 micrometer (CO 2), the onset of material removal has been shown to be delayed with respect to irradiation and the magnitude of the generated stress transients are consistent with a model for explosive material removal. Upon consideration of the threshold radiant exposure for ablation, it appears that the mechanism and dynamics of these processes are controlled by explosive boiling as the tissue water is likely to be significantly superheated. To examine this issue further, we employed time- resolved optical interferometry to measure the surface displacement generated by Q-sw Er:YSGG laser irradiation of pure water for radiant exposures below the ablation threshold. This was done to directly measure the dynamic thermal expansion and interphase mass transfer generated by pulsed laser heating. These results are compared to a model which computes the dynamic thermal field within a semi-infinite pool of water undergoing pulsed irradiation while subject to a surface heat flux condition given by kinetic theory. We find that the measured mass fluxes exceed that predicted by simple kinetic theory arguments. The implications of the experimental and model results to pulsed laser ablation of tissue are discussed. ©2003 Copyright SPIE - The International Society for Optical Engineering.

The efficiency of electroporation treatments depends on the application of a critical electric field over the targeted tissue volume. Both the electric field and temperature distribution strongly depend on the tissue-specific electrical properties, which both differ between patients in healthy and malignant tissues and change in an electric field-dependent manner from the electroporation process itself. Therefore, tissue property estimations are paramount for treatment planning with electroporation therapies. Ex vivo methods to find electrical tissue properties often misrepresent the targeted tissue, especially when translating results to tumors. A voltage ramp is an in situ method that applies a series of increasing electric potentials across treatment electrodes and measures the resulting current. Here, we develop a robust deep neural network, trained on finite element model simulations, to directly predict tissue properties from a measured voltage ramp. There was minimal test error (R 2 > 0.94 ; p < 0.0001) in three important electric tissue properties. Further, our model was validated to correctly predict the complete dynamic conductivity curve in a previously characterized ex vivo liver model (R 2 > 0.93 ; p < 0.0001) within 100 s from probe insertion, showing great utility for a clinical application. Lastly, we characterize the first reported electrical tissue properties of lung tumors from five canine patients (R 2 > 0.99 ; p < 0.0001). We believe this platform can be incorporated prior to treatment to quickly ascertain patient-specific tissue properties required for electroporation treatment planning models or real-time treatment prediction algorithms. Further, this method can be used over traditional ex vivo methods for in situ tissue characterization with clinically relevant geometries. [ABSTRACT FROM AUTHOR]