Irreversible Electroporation: An In Vivo Study Within the Dorsal Skin Fold Chamber

2011 ◽  
Author(s):  
Zhenpeng Qin ◽  
Jing Jiang ◽  
Gary Long ◽  
John C. Bischof
Keyword(s):  
Protein Denaturation ◽  
Irreversible Electroporation ◽  
Molecular Transport ◽  
Electrical Field ◽  
Irreversible Damage ◽  
Skin Fold ◽  
Electrical Pulses ◽  
Dorsal Skin Fold Chamber ◽  
Fast Procedure

Electroporation has been traditionally used to enhance molecular transport into cells (e.g. gene therapy) and through tissues (e.g. skin) by creating reversible pores with short electrical pulses [1]. Increasing the parameters (electrical field, pulse duration and number) can induce irreversible damage to the cells and tissue. Recently, irreversible electroporation (IRE) has been investigated as a new tumor ablation method [2]. The advantages of the IRE include the simple and fast procedure (train of μs pulses), sharp demarcation between treated and untreated regions, destruction of tumor cells while preserving the connective tissue, and minimal effect of immune response on treatment efficacy [3]. The unique interaction of electrical field with heterogeneous structures prevents damage to nerves, blood vessels and ducts [4]. IRE has been claimed to produce negligible thermal injury and protein denaturation typical to thermal ablation [5]. However, how each electroporation parameter in IRE affects tumor destruction and the possibility of heating remains to be studied in tumors vivo.

Irreversible Electroporation: An In Vivo Study with Dorsal Skin Fold Chamber

2012 ◽  
Vol 41 (3) ◽  
pp. 619-629 ◽  
Author(s):  
Zhenpeng Qin ◽  
Jing Jiang ◽  
Gary Long ◽  
Bruce Lindgren ◽  
John C. Bischof
Keyword(s):  
Irreversible Electroporation ◽  
In Vivo Study ◽  
Dorsal Skin ◽  
Skin Fold ◽  
Dorsal Skin Fold Chamber

scholarly journals Numerical simulation modeling of the irreversible electroporation treatment zone for focal therapy of prostate cancer, correlation with whole-mount pathology and T2-weighted MRI sequences

2019 ◽  
Vol 11 ◽  
pp. 175628721985230 ◽  
Author(s):  
Matthijs J. Scheltema ◽  
Tim J. O’Brien ◽  
Willemien van den Bos ◽  
Daniel M. de Bruin ◽  
Rafael V. Davalos ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Irreversible Electroporation ◽  
Prostate Tissue ◽  
Human Prostate ◽  
Ablation Zone ◽  
Electrical Field ◽  
Whole Mount ◽  
Human Prostate Tissue ◽  
Mri Sequences

Background: At present, it is not possible to predict the ablation zone volume following irreversible electroporation (IRE) for prostate cancer (PCa). This study aimed to determine the necessary electrical field threshold to ablate human prostate tissue in vivo with IRE. Methods: In this prospective multicenter trial, patients with localized PCa were treated with IRE 4 weeks before their scheduled radical prostatectomy. In 13 patients, numerical models of the electrical field were generated and compared with the ablation zone volume on whole-mount pathology and T2-weighted magnetic resonance imaging (MRI) sequences. Volume-generating software was used to calculate the ablation zone volumes on histology and MRI. The electric field threshold to ablate prostate tissue was determined for each patient. Results: A total of 13 patients were included for histological and simulation analysis. The median electrical field threshold was 550 V/cm (interquartile range 383–750 V/cm) for the software-generated histology volumes. The median electrical field threshold was 500 V/cm (interquartile range 386–580 V/cm) when the ablation zone volumes were used from the follow-up MRI. Conclusions: The electrical field threshold to ablate human prostate tissue in vivo was determined using whole-mount pathology and MRI. These thresholds may be used to develop treatment planning or monitoring software for IRE prostate ablation; however, further optimization of simulation methods are required to decrease the variance that was observed between patients.

scholarly journals Cardiac impact of high-frequency irreversible electroporation using an asymmetrical waveform on liver in vivo

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jing Li ◽  
Jingjing Wang ◽  
Xiaobo Zhang ◽  
Xiao Zhang ◽  
Hongmei Gao ◽  
...  
Keyword(s):  
Muscle Relaxant ◽  
High Frequency ◽  
Liver Tissue ◽  
Irreversible Electroporation ◽  
Normal Liver ◽  
Electrical Signal ◽  
Cardiac Complications ◽  
Cardiac Damage ◽  
Electrical Pulses

Abstract Background High-Frequency Irreversible Electroporation (H-FIRE) is a novel technology for non-thermal ablation. Different from Irreversible electroporation (IRE), H-FIRE delivers bipolar electrical pulses without muscle contraction and does not cause electrolysis. Currently, little is known regarding the cardiac safety during the administration of H-FIRE on liver. The aim of this study was to evaluate the changes of electrocardiogram (ECG) and biomarkers of cardiac damage during asymmetrical waveform of H-FIRE therapy in vivo. Methods The swines (n = 7) in IRE group, which used 100 pulses (2200 V, 100–100 μs configuration), were administrated with muscle relaxant under anesthesia. In the absence of muscle relaxant, 7 swines in H-FIRE group were performed with 2400 pulses (3000 V, 5–3–3–5 μs configuration). Midazolam (0.5 mg/kg) and xylazine hydrochloride (20 mg/kg) were given to induce sedation, followed by Isoflurane (2.5%, 100% oxygen, 3 L/min) to maintain sedation in all the swines. Limb lead ECG recordings were analyzed by two electrophysiologists to judge the arrhythmia. Cardiac and liver tissue was examined by pathology technique. Results The ablation zones were larger in H-FIRE than IRE. Both IRE and H-FIRE did not affect the autonomous cardiac rhythm. Even when the electrical signal of IRE and H-FIRE fell on ventricular vulnerable period. Moreover, cTnI in IRE group showed an increase in 4 h after ablation, and decreased to baseline 72 h after ablation. However, cTnI showed no significant change during the administration of H-FIRE. Conclusions The study suggests an asymmetrical waveform for H-FIRE is a promising measure for liver ablation. The results were based on normal liver and the swines without potential cardiac diseases. With the limitations of these facts, asymmetrical waveform for H-FIRE of liver tissue seems relatively safe without major cardiac complications. The safety of asymmetrical waveform for H-FIRE needs to evaluate in future.

In-vivo monitoring of infection via implantable microsensors: a pilot study

2018 ◽  
Vol 63 (4) ◽  
pp. 421-426 ◽  
Author(s):  
Andrej Ring ◽  
Heiko Sorg ◽  
Andreas Weltin ◽  
Daniel J. Tilkorn ◽  
Jochen Kieninger ◽  
...  
Keyword(s):  
Lactate Concentration ◽  
Reference Electrode ◽  
Wafer Level ◽  
Skin Fold ◽  
Dorsal Skin Fold Chamber ◽  
Foreign Materials ◽  
The Given ◽  
Implantable Microsensors ◽  
Level Process

Abstract The most common complication after implantation of foreign material is infection, leading to implant failure and severe patient discomfort. Smoldering-infections proceed inapparently and might not get verified by radiological diagnostics. Early identification of this type of infection might significantly reduce the rate of complications. Therefore, we manufactured a microsensor strip in a hybrid of thin-film and laminate technology in a wafer-level process. It comprises electrochemical, amperometric microsensors for glucose, oxygen and lactate as well as an integrated reference electrode. Microsensors have been implanted in the mouse dorsal skin fold chamber, which got inoculated with a human-pathogen bacterial strain. A selective signal could be measured for all parameters and time points. The infection led to measurable changes of the wound environment as given by a decrease of the oxygen- as well as the glucose-concentration while the lactate concentration increased markedly over time. The given results in this study are the first hints on a promising new tool and should therefore be interpreted as a proof of the principle to show the functionality of the microsensors in an in vivo setting. These microsensors could be used to monitor smoldering infections of implantable foreign materials reducing foreign implant associated complications.

Electrical Field and Temperature Model of Nonthermal Irreversible Electroporation in Heterogeneous Tissues

2009 ◽  
Vol 131 (7) ◽  
Author(s):  
Charlotte Daniels ◽  
Boris Rubinsky
Keyword(s):  
Blood Vessels ◽  
Irreversible Electroporation ◽  
Surrounding Tissue ◽  
Electrical Field ◽  
Irreversible Damage ◽  
Minimally Invasive Surgical ◽  
Dimensional Finite Element ◽  
Nonthermal Irreversible Electroporation ◽  
Molecular Surgery ◽  
Heterogeneous Tissues

Nonthermal irreversible electroporation (NTIRE) is a new minimally invasive surgical technique that is part of the emerging field of molecular surgery, which holds the potential to treat diseases with unprecedented accuracy. NTIRE utilizes electrical pulses delivered to a targeted area, producing irreversible damage to the cell membrane. Because NTIRE does not cause thermal damage, the integrity of all other molecules, collagen, and elastin in the targeted area is preserved. Previous theoretical studies have only examined NTIRE in homogeneous tissues; however, biological structures are complex collections of diverse tissues. In order to develop electroporation as a precise treatment in clinical applications, realistic models are necessary. Therefore, the purpose of this study was to refine electroporation as a treatment by examining the effect of NTIRE in heterogeneous tissues of the prostate and breast. This study uses a two-dimensional finite element solution of the Laplace and bioheat equations to examine the effects of heterogeneities on electric field and temperature distribution. Three different heterogeneous structures were taken into account: nerves, blood vessels, and ducts. The results of this study demonstrate that heterogeneities significantly impact both the temperature and electrical field distribution in surrounding tissues, indicating that heterogeneities should not be neglected. The results were promising. While the surrounding tissue experienced a high electrical field, the axon of the nerve, the interior of the blood vessel, and the ducts experienced no electrical field. This indicates that blood vessels, nerves, and lactiferous ducts adjacent to a tumor treated with electroporation will survive, while the cancerous lesion is ablated. This study clearly demonstrates the importance of considering heterogeneity in NTIRE applications.

Nonthermal Irreversible Electroporation for Tissue Decellularization

2010 ◽  
Vol 132 (9) ◽  
Author(s):  
Mary Phillips ◽  
Elad Maor ◽  
Boris Rubinsky
Keyword(s):  
Thermal Damage ◽  
Irreversible Electroporation ◽  
Electrical Parameters ◽  
Irreversible Damage ◽  
Tissue Scaffold ◽  
Electrical Fields ◽  
Nonthermal Irreversible Electroporation ◽  
Tissue Scaffolding ◽  
Living Tissues

Tissue scaffolding is a key component for tissue engineering, and the extracellular matrix (ECM) is nature’s ideal scaffold material. A conceptually different method is reported here for producing tissue scaffolds by decellularization of living tissues using nonthermal irreversible electroporation (NTIRE) pulsed electrical fields to cause nanoscale irreversible damage to the cell membrane in the targeted tissue while sparing the ECM and utilizing the body’s host response for decellularization. This study demonstrates that the method preserves the native tissue ECM and produces a scaffold that is functional and facilitates recellularization. A two-dimensional transient finite element solution of the Laplace and heat conduction equations was used to ensure that the electrical parameters used would not cause any thermal damage to the tissue scaffold. By performing NTIRE in vivo on the carotid artery, it is shown that in 3 days post NTIRE the immune system decellularizes the irreversible electroporated tissue and leaves behind a functional scaffold. In 7 days, there is evidence of endothelial regrowth, indicating that the artery scaffold maintained its function throughout the procedure and normal recellularization is taking place.

Fibrinolytic, Anti-Inflammatory and Cytotoxic Potentialities of Extracts and Chemical Constituents of Manglicolous Lichen, Graphis ajarekarii Patw. & C. R. Kulk

2020 ◽  
Vol 10 (1) ◽  
pp. 87-93 ◽  
Author(s):  
Vinay Bharadwaj Tatipamula ◽  
Girija Sastry Vedula
Keyword(s):  
Protein Denaturation ◽  
Biological Activities ◽  
Chemical Constituents ◽  
Fibrin Clot ◽  
Hydroalcoholic Extract ◽  
Paw Oedema ◽  
Anti Inflammatory ◽  
Rat Paw ◽  
Rat Paw Oedema

Background: Lichens which are betide to mangroves are termed as Manglicolous Lichens (ML). As these ML are habituated under stress conditions, they are screened for unique metabolites and biological activities. Objective: The study aimed to establish the chemical and biological profile of ML, Graphis ajarekarii. Methods: The Ethyl Acetate Extract of G. ajarekarii (EAE) was subjected to chromatographic techniques and the obtained isolates were characterized by spectroscopic analysis. The hydroalcoholic extract of G. ajarekarii (AE), EAE, isolates and Hydroalcoholic Extract of host (HE) were evaluated for fibrinolytic (fibrin clot method), in vitro (protein denaturation method) and in vivo (formalin-induced rat paw oedema assay), anti-inflammatory and cytotoxicity (MTT assay) activities. Results: Chemical investigation of the EAE led to the isolation of two known compounds namely atranorin (1) and ribenone (2), which were confirmed by spectral data. The AE and EAE gradually lysed the fibrin clot with 94.54 and 65.07%, respectively, at 24 h. The AE inhibited protein denaturation of about 88.06%, while the standard (Indomethacin) with 93.62%. Similarly, the in vivo antiinflammatory analysis of AE (200 mg/mL) showed potent reduction of rat paw oedema than the standard, whereas EAE and 1 depicted moderate depletion. In addition, the AE revealed prominence inhibition on MCF-7, DU145 and K-562 with IC50 values of 69.5, 42.5 and 38 µg/mL, respectively, whereas the HE exhibited mild inhibitory profile against fibrin clot, inflammation and cancer. Conclusion: From the results, it can be concluded that the G. ajarekarii has an aptitude to act against coagulation, inflammation and cancer cells.

scholarly journals Mathematical model for the thermal enhancement of radiation response: thermodynamic approach

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Adriana M. De Mendoza ◽  
Soňa Michlíková ◽  
Johann Berger ◽  
Jens Karschau ◽  
Leoni A. Kunz-Schughart ◽  
...  
Keyword(s):  
Protein Denaturation ◽  
Collateral Damage ◽  
Hyperthermia Treatment ◽  
Reversible Process ◽  
Technological Advances ◽  
Thermal Enhancement ◽  
Main Driver ◽  
Definition Of

AbstractRadiotherapy can effectively kill malignant cells, but the doses required to cure cancer patients may inflict severe collateral damage to adjacent healthy tissues. Recent technological advances in the clinical application has revitalized hyperthermia treatment (HT) as an option to improve radiotherapy (RT) outcomes. Understanding the synergistic effect of simultaneous thermoradiotherapy via mathematical modelling is essential for treatment planning. We here propose a theoretical model in which the thermal enhancement ratio (TER) relates to the cell fraction being radiosensitised by the infliction of sublethal damage through HT. Further damage finally kills the cell or abrogates its proliferative capacity in a non-reversible process. We suggest the TER to be proportional to the energy invested in the sensitisation, which is modelled as a simple rate process. Assuming protein denaturation as the main driver of HT-induced sublethal damage and considering the temperature dependence of the heat capacity of cellular proteins, the sensitisation rates were found to depend exponentially on temperature; in agreement with previous empirical observations. Our findings point towards an improved definition of thermal dose in concordance with the thermodynamics of protein denaturation. Our predictions well reproduce experimental in vitro and in vivo data, explaining the thermal modulation of cellular radioresponse for simultaneous thermoradiotherapy.

scholarly journals Effect of Processing on Fish Protein Antigenicity and Allergenicity

Foods ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 969
Author(s):  
Xingyi Jiang ◽  
Qinchun Rao
Keyword(s):  
Fish Species ◽  
Protein Denaturation ◽  
Ex Vivo ◽  
Protein Solubility ◽  
Future Research ◽  
Food Protein ◽  
In Vivo Evaluation ◽  
Fish Allergy

Fish allergy is a life-long food allergy whose prevalence is affected by many demographic factors. Currently, there is no cure for fish allergy, which can only be managed by strict avoidance of fish in the diet. According to the WHO/IUIS Allergen Nomenclature Sub-Committee, 12 fish proteins are recognized as allergens. Different processing (thermal and non-thermal) techniques are applied to fish and fishery products to reduce microorganisms, extend shelf life, and alter organoleptic/nutritional properties. In this concise review, the development of a consistent terminology for studying food protein immunogenicity, antigenicity, and allergenicity is proposed. It also summarizes that food processing may lead to a decrease, no change, or even increase in fish antigenicity and allergenicity due to the change of protein solubility, protein denaturation, and the modification of linear or conformational epitopes. Recent studies investigated the effect of processing on fish antigenicity/allergenicity and were mainly conducted on commonly consumed fish species and major fish allergens using in vitro methods. Future research areas such as novel fish species/allergens and ex vivo/in vivo evaluation methods would convey a comprehensive view of the relationship between processing and fish allergy.

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