Compact High-Voltage AC Generator with Pulse Transformer for High-Frequency Irreversible Electroporation (H-FIRE)

This paper is focused on a design of a high-voltage (HV) generator, which is proposed for a high-frequency irreversible electroporation (H-FIRE). The generator produces bursts of bipolar symmetrical pulses. Most HV sources used for cell electroporation are based on a controlled discharge of a capacitor into a resistive load. This solution is very simple, but it is associated with a certain risk of an uncontrolled discharge of the capacitor. We present a different type of the generator, where a DC-AC inverter with pulse transformer is used and where the mentioned risk is eliminated. Our generator is able to deliver bursts with variable length from 50 to 150 μs and a gap between bursts can be set from 0.5 to 1.5 s. Pulse frequency can be varied from 65 to 470 kHz and the output voltage is controlled in two ranges from 0 to 1.3 kV or from 0 to 2.5 kV. Results are presented with resistive load and with tissue impedance load.

Optimized radiofrequency lesions through local impedance guidance for effective cavo-tricuspid isthmus ablation in typical right atrial flutter: data from the CHARISMA registry

Funding Acknowledgements Type of funding sources: None. Background Radiofrequency (RF) catheter ablation of the cavo-tricuspid isthmus (CTI) is an established treatment for typical right atrial flutter (RAFL). However, whether local tissue impedance (LI) is able to predict effective CTI ablation and what LI drop values during ablation should be used to judge a lesion as effective remains to be established. Purpose We aimed to investigate the ability of LI to predict ablation efficacy in patients (pts) with RAFL and to characterize the CTI in terms of LI. Methods Consecutive pts undergoing RAFL ablation from the CHARISMA registry were enrolled at 9 centers. A novel RF ablation catheter with dedicated algorithm (DirectSense - DS -) was used to measure LI at the distal electrode of this catheter. RF applications (RFC) were targeted to a minimum LI drop of 10 Ω within 30 seconds and were stopped when a maximum cutoff LI drop of <40 Ω was observed. Successful single RFC was defined according with a split in two separate potentials (SPL), reduction of voltage (RedV) by at least 50% or changes at unipolar EGM (UPC). Agreement among criteria was evaluated. Ablation endpoint was the creation of bidirectional conduction block (BDB) across the isthmus. Results A total of 279 ablation spot lesions were delivered in 30 pts (mean RFC 9 ± 6 lesions per pt): 106 (38%) at anterior, 115 (41%) at mid and 58 (21%) at posterior portions of the CTI. BDB was obtained in all cases and no complications were observed. The median RFC delivery time was 30 [19–45] seconds per lesion. 132 (47%), 150 (54%) and 86 (31%) ablation spots were effective according with SPL, RedV and UPC, respectively. Complete agreement of all the criteria was reached in 70% of the cases. The mean LI was 104.4 ± 11Ω prior to ablation and 92.1 ± 11Ω after ablation (p < 0.0001, mean absolute LI drop 12.2 ± 7Ω, mean time to LI drop 13 ± 8 seconds). Effective ablation spots showed a higher LI drop compared with ineffective sites at each single criteria (16.6 ± 7Ω vs 8.3 ± 4Ω for SPL, p < 0.0001; 16.1 ± 6Ω vs 7.8 ± 5Ω at for RedV, p < 0.0001; 19 ± 6Ω vs 9.2 ± 4Ω for UPC, p < 0.0001) and LI drop values significantly increase according to the number of criteria satisfied (ranging from 7.5Ω % -no criteria- to 19.1 -all criteria-). A 15Ω cut-off value for LI (AUC 0.91, sensitivity = 67%, specificity = 92%, p < 0.0001) was associated with the achievement of all criteria with an OR of 21.9 (95%CI: 11.1 to 43.5, p < 0.0001) and a positive predictive value of 76%. Starting LI and LI drop seem to be higher at mid-septal areas. Conclusion In our preliminary experience, a LI-guided approach of CTI seems to be safe and effective in RAFL ablation. The magnitude of LI drop was associated with effective lesion formation and conduction block and could be used as a marker of ablation efficacy.

Ex-Vivo Detection of Breast Cancer with a Bio-Impedance Sensor

Bioimpedance is the opposition to flow of an applied electrical current through biological tissues1. Our research group designed and fabricated bipolar micro-sensors on the tip of a silicone probe, capable of measuring biological tissue impedance. It is known that the bioimpedance of cultured cancer cells differs substantially from that of healthy cell lines. We hypothesised that the bioimpedance of cancer in surgically excised human tissue would be significantly different to surrounding healthy tissue. To test this hypothesis, we designed a study to evaluate the bioimpedance of healthy and diseased breast tissue in surgically excised breast specimens. This manuscript reports the outcome of this study.

Electrical bioimpedance: from the past to the future

This year, 2021, marks the “coming of age” for JoEB with its indexing in PubMed Central. It is also a century since some of the earliest studies on tissue impedance. This editorial briefly reviews the time-line of research in the field to mark this occasion.

Investigation of frequency characteristics of biological tissues impedance

The problem of identifying informative signs of biological tissues viability using the impedance measurement method is formulated. At present there is no instrumental base that makes it possible in an operational setting to diagnose the ability of biological tissue to heal itself after injury and damage as a result of thermal exposure, gunshot wound or prolonged compression. It is shown in this article that development of methods and tools for instrumental diagnostics in medical diagnostic practice is an important modern challenge. The results of experimental measurements of impedance characteristics in the frequency range of 20 Hz – 2.0 MHz are presented. The frequency dependences of the modulus of voltage on biological tissues of plant origin are analyzed in its intact state, as well as after exposure of biological tissue samples in a freezer at time intervals from 15 minutes to 2 hours. A comparative analysis of the obtained frequency dependences is carried out. A significant difference between the frequency dependences of the voltage modulus on biological tissues and the frequency dependence of the voltage modulus on an isotonic solution is shown. The concept is introduced that the degree of difference between the frequency distribution of the biological tissue impedance module from the impedance module of an isotonic solution can serve as a criterion for assessing the degree of damage to biological tissue. A conclusion is made about the advisability of developing the impedance measurement method as a method for diagnosing the viability of biological tissue; it is shown that the most promising approach to the development of impedance measurement methods is the analysis of transient processes when biological tissue is disturbed by small electric current pulses.

NON-INVASIVE LIVER BLOOD FLOW ASSESSMENT DEVICE

Клетки печени наиболее подвержены отрицательным последствиям, т.к. печень принимает активное участие в обменных процессах и в выведении из организма вредных и токсичных веществ. С появлением методов исследования, позволяющих изучать локальный кровоток в различных отделах печени, значительно увеличились возможности распознавания патологии. Реогепатография позволяет оценить функциональное состояние сосудов печени, их тонус, эластичность и кровенаполнение, объемную скорость кровотока и выявить застойные явления в венах. Целью данной статьи являлась разработка технического проекта по созданию прибора для неинвазивной оценки кровотока печени. Разработанный прибор оценивает кровоток печени по изменению ее удельного сопротивления. Метод оценки - электроимпедансная реогепатография. Данный метод позволяет регистрировать динамические изменения в импедансе ткани, вызванные изменениями кровотока печени в период сердечного цикла при пропускании через ткань электрического тока высокой частоты и малой амплитуды. Предложена оптимальная конструкция реографа, состоящего из системы электродов, источника тока, биоусилителя, системы сбора данных и блока питания. Электродная система состоит из 6 электродов (2 токовых и 4 измерительных). Портативный прибор позволяет измерять импеданс в диапазоне 0-250 Ом Liver cells are most exposed to negative consequences, because the liver takes an active part in metabolic processes and in the removal of harmful and toxic substances from the body. With the introduction of research methods that allow the study of local blood flow in different parts of the liver, the ability to recognize pathology has increased significantly. Rheohepatography can assess the functional state of liver vessels, their tone, elasticity and blood flow, the volume rate of blood flow and to identify stagnation in the veins. The purpose of this article was to develop a technical project to create a device for non-invasive assessment of blood flow in the liver. The developed device evaluates blood flow of the liver by changing its resistivity. The method of evaluation is electroimpedance rheopathography. This method allows to register dynamic changes in tissue impedance caused by changes in blood flow of the liver during the cardiac cycle when passing through the tissue of high frequency and small amplitude electrical current. The optimal design of the rheograph, consisting of a system of electrodes, current source, bioamplifier, data acquisition system and power supply unit is proposed. The electrode system consists of 6 electrodes (2 current and 4 measurement electrodes). The portable device allows measuring impedance in the range of 0-250 Ohm

AC Pulsed Field Ablation Is Feasible and Safe in Atrial and Ventricular Settings: A Proof-of-Concept Chronic Animal Study

IntroductionPulsed field ablation (PFA) exploits the delivery of short high-voltage shocks to induce cells death via irreversible electroporation. The therapy offers a potential paradigm shift for catheter ablation of cardiac arrhythmia. We designed an AC-burst generator and therapeutic strategy, based on the existing knowledge between efficacy and safety among different pulses. We performed a proof-of-concept chronic animal trial to test the feasibility and safety of our method and technology.MethodsWe employed 6 female swine – weight 53.75 ± 4.77 kg – in this study. With fluoroscopic and electroanatomical mapping assistance, we performed ECG-gated AC-PFA in the following settings: in the left atrium with a decapolar loop catheter with electrodes connected in bipolar fashion; across the interventricular septum applying energy between the distal electrodes of two tip catheters. After procedure and 4-week follow-up, the animals were euthanized, and the hearts were inspected for tissue changes and characterized. We perform finite element method simulation of our AC-PFA scenarios to corroborate our method and better interpret our findings.ResultsWe applied square, 50% duty cycle, AC bursts of 100 μs duration, 100 kHz internal frequency, 900 V for 60 pulses in the atrium and 1500 V for 120 pulses in the septum. The inter-burst interval was determined by the native heart rhythm – 69 ± 9 bpm. Acute changes in the atrial and ventricular electrograms were immediately visible at the sites of AC-PFA – signals were elongated and reduced in amplitude (p < 0.0001) and tissue impedance dropped (p = 0.011). No adverse event (e.g., esophageal temperature rises or gas bubble streams) was observed – while twitching was avoided by addition of electrosurgical return electrodes. The implemented numerical simulations confirmed the non-thermal nature of our AC-PFA and provided specific information on the estimated treated area and need of pulse trains. The postmortem chest inspection showed no peripheral damage, but epicardial and endocardial discolorations at sites of ablation. T1-weighted scans revealed specific tissue changes in atria and ventricles, confirmed to be fibrotic scars via trichrome staining. We found isolated, transmural and continuous scars. A surviving cardiomyocyte core was visible in basal ventricular lesions.ConclusionWe proved that our method and technology of AC-PFA is feasible and safe for atrial and ventricular myocardial ablation, supporting their systematic investigation into effectiveness evaluation for the treatment of cardiac arrhythmia. Further optimization, with energy titration or longer follow-up, is required for a robust atrial and ventricular AC-PFA.

Imaging fascicular organization of rat sciatic nerves with fast neural electrical impedance tomography

Imaging compound action potentials (CAPs) in peripheral nerves could help avoid side effects in neuromodulation by selective stimulation of identified fascicles. Existing methods have low resolution, limited imaging depth, or are invasive. Fast neural electrical impedance tomography (EIT) allows fascicular CAP imaging with a resolution of <200 µm, <1 ms using a non-penetrating flexible nerve cuff electrode array. Here, we validate EIT imaging in rat sciatic nerve by comparison to micro-computed tomography (microCT) and histology with fluorescent dextran tracers. With EIT, there are reproducible localized changes in tissue impedance in response to stimulation of individual fascicles (tibial, peroneal and sural). The reconstructed EIT images correspond to microCT scans and histology, with significant separation between the fascicles (p < 0.01). The mean fascicle position is identified with an accuracy of 6% of nerve diameter. This suggests fast neural EIT can reliably image the functional fascicular anatomy of the nerves and so aid selective neuromodulation.