Helena Cindrič

University of Ljubljana

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Damijan Miklavčič

University of Ljubljana

Bor Kos

University of Ljubljana

F. Cornélis

Memorial Sloan Kettering Cancer Center

Lukas Philipp Beyer

University Hospital Regensburg

Michael Moche

Helios Park-Klinikum Leipzig

Philipp Wiggermann

Klinikum Braunschweig

Panchatcharam Mariappan

Indian Institute of Technology Tirupati

Paul A. Iaizzo

University of Minnesota

Alessandro Gasbarrini

Istituto Ortopedico Rizzoli

Tadej Krmac

University of Ljubljana

Cooperative Institutions

University of Ljubljana

Institute of Oncology Ljubljana

Memorial Sloan Kettering Cancer Center

University of Minnesota

Istituto Ortopedico Rizzoli

University of Bologna

Cornell University

Weill Cornell Medicine

Ljubljana University Medical Centre

Medtronic (Ireland)

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Optimization of Transpedicular Electrode Insertion for Electroporation-Based Treatments of Vertebral Tumors

Cancers (2022)

Helena Cindrič Damijan Miklavčič F. Cornélis Bor Kos

Electroporation-based treatments such as electrochemotherapy and irreversible electroporation ablation have sparked interest with respect to their use in medicine. Treatment planning involves determining the best possible electrode positions and voltage amplitudes to ensure treatment of the entire clinical target volume (CTV). This process is mainly performed manually or with computationally intensive genetic algorithms. In this study, an algorithm was developed to optimize electrode positions for the electrochemotherapy of vertebral tumors without using computationally intensive methods. The algorithm considers the electric field distribution in the CTV, identifies undertreated areas, and uses this information to iteratively shift the electrodes from their initial positions to cover the entire CTV. The algorithm performs successfully for different spinal segments, tumor sizes, and positions within the vertebra. The average optimization time was 71 s with an average of 4.9 iterations performed. The algorithm significantly reduces the time and expertise required to create a treatment plan for vertebral tumors. This study serves as a proof of concept that electrode positions can be determined (semi-)automatically based on the spatial information of the electric field distribution in the target tissue. The algorithm is currently designed for the electrochemotherapy of vertebral tumors via a transpedicular approach but could be adapted for other anatomic sites in the future.

Electrochemotherapy

Electrode array

Irreversible Electroporation

10.3390/cancers14215412

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Investigation of safety for electrochemotherapy and irreversible electroporation ablation therapies in patients with cardiac pacemakers

BioMedical Engineering OnLine (2020)

Tomaž Jarm Tadej Krmac Ratko Magjarević Bor Kos Helena Cindrič

Abstract Background The effectiveness of electrochemotherapy of tumors (ECT) and of irreversible electroporation ablation (IRE) depends on different mechanisms and delivery protocols. Both therapies exploit the phenomenon of electroporation of the cell membrane achieved by the exposure of the cells to a series of high-voltage electric pulses. Electroporation can be fine-tuned to be either reversible or irreversible, causing the cells to either survive the exposure (in ECT) or not (in IRE), respectively. For treatment of tissues located close to the heart (e.g., in the liver), the safety of electroporation-based therapies is ensured by synchronizing the electric pulses with the electrocardiogram. However, the use of ECT and IRE remains contraindicated for patients with implanted cardiac pacemakers if the treated tissues are located close to the heart or the pacemaker. In this study, two questions are addressed: can the electroporation pulses interfere with the pacemaker; and, can the metallic housing of the pacemaker modify the distribution of electric field in the tissue sufficiently to affect the effectiveness and safety of the therapy? Results The electroporation pulses induced significant changes in the pacemaker ventricular pacing pulse only for the electroporation pulses delivered during the pacing pulse itself. No residual effects were observed on the pacing pulses following the electroporation pulses for all tested experimental conditions. The results of numerical modeling indicate that the presence of metal-encased pacemaker in immediate vicinity of the treatment zone should not impair the intended effectiveness of ECT or IRE even when the casing is in direct contact with one of the active electrodes. Nevertheless, the contact between the casing and the active electrode should be avoided due to significant tissue heating at the site of the other active electrode for the IRE protocol and may cause the pulse generator to fail to deliver the pulses due to excessive current draw. Conclusions The observed effects of electroporation pulses delivered in close vicinity of the pacemaker or its electrodes do not indicate adverse consequences for either the function of the pacemaker or the treatment outcome. These findings should contribute to making electroporation-based treatments accessible also to patients with implanted cardiac pacemakers.

Irreversible Electroporation

Electrochemotherapy

10.1186/s12938-020-00827-7

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Optimization of transpedicular electrode insertion for electro-poration-based treatments of spinal tumors

Figshare (2022)

Helena Cindrič Damijan Miklavčič F. Cornélis Bor Kos

The dataset (models.zip) contains 36 COMSOL Multiphysics files (.mph file extension) containing anatomically realistic models of single vertebrae with spherical tumors in the vertebral body. The models are prepared for simulation of electric field distribution during electrochemotherapy of vertebral tumors. The models can be used with the algorithm described in the research article "Optimization of transpedicular electrode insertion for electroporation-based treatments of spinal tumors" by Helena Cindrič et al. The source code of the algorithm and a script for testing (for use in MATLAB connected to COMSOL via LiveLink) are included in a separate file (codes.zip).

10.6084/m9.figshare.21270111

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Peri-tumoral Metallic Implants Reduce the Efficacy of Irreversible Electroporation for the Ablation of Colorectal Liver Metastases

CardioVascular and Interventional Radiology (2019)

F. Cornélis Helena Cindrič Bor Kos Masashi Fujimori Elena N. Petre

Irreversible Electroporation

Tumor progression

Univariate analysis

Microwave ablation

Electrochemotherapy

10.1007/s00270-019-02300-y

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Determination of lethal electric field threshold for pulsed field ablation in ex vivo perfused porcine and human hearts

Frontiers in Cardiovascular Medicine (2023)

Bor Kos Lars M. Mattison David A. Ramirez Helena Cindrič Daniel C. Sigg

Pulsed field ablation is an emerging modality for catheter-based cardiac ablation. The main mechanism of action is irreversible electroporation (IRE), a threshold-based phenomenon in which cells die after exposure to intense pulsed electric fields. Lethal electric field threshold for IRE is a tissue property that determines treatment feasibility and enables the development of new devices and therapeutic applications, but it is greatly dependent on the number of pulses and their duration.In the study, lesions were generated by applying IRE in porcine and human left ventricles using a pair of parallel needle electrodes at different voltages (500-1500 V) and two different pulse waveforms: a proprietary biphasic waveform (Medtronic) and monophasic 48 × 100 μs pulses. The lethal electric field threshold, anisotropy ratio, and conductivity increase by electroporation were determined by numerical modeling, comparing the model outputs with segmented lesion images.The median threshold was 535 V/cm in porcine ((N = 51 lesions in n = 6 hearts) and 416 V/cm in the human donor hearts ((N = 21 lesions in n = 3 hearts) for the biphasic waveform. The median threshold value was 368 V/cm in porcine hearts ((N = 35 lesions in n = 9 hearts) cm for 48 × 100 μs pulses.The values obtained are compared with an extensive literature review of published lethal electric field thresholds in other tissues and were found to be lower than most other tissues, except for skeletal muscle. These findings, albeit preliminary, from a limited number of hearts suggest that treatments in humans with parameters optimized in pigs should result in equal or greater lesions.

Ex vivo

10.3389/fcvm.2023.1160231

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Retrospective study for validation and improvement of numerical treatment planning of irreversible electroporation ablation for treatment of liver tumors

Figshare (2021)

Helena Cindrič Panchatcharam Mariappan Lukas Philipp Beyer Philipp Wiggermann Michael Moche

Supplementary data for 18 cases of hepatic tumors, treated with percutaneous irreversible electroporation ablation.
- segmentation.nii (NIfTI format):Tissue masks, segmented from pre-interventional CECT.
- liver_interv.vtk (VTK format):Liver surface model, obtained from pre-interventional CT segmentation, registered to computation domain
- tumor_interv.vtk (VTK format):Tumor surface model, obtained from pre-interventional CT segmentation, registered to computation domain
- liver_follow_trans.vtk (VTK format):Liver surface model, obtained from 6-week follow-up MRI, registered to computation domain
- segmented_lesion_trans.vtk (VTK format):Ablation zone surface model, obtained from 6-week follow-up MRI, registered to computation domain
- field400-field900.vtk (VTK format):Computed electric field surfaces obtained by thresholding the volumetric data with 400, 500, 600, 700, 800, 900 V/cm

Irreversible Electroporation

10.6084/m9.figshare.12961646

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Ireverzibilna elektroporacija kot metoda ablacije mehkih tkiv: pregled in izzivi pri uporabi v kliničnem okolju

Slovenian Medical Journal (2021)

Helena Cindrič Bor Kos Damijan Miklavčič

Koncept ireverzibilne elektroporacije kot samostojne ablacijske metode je bil prvič predstavljen pred petnajstimi leti. Ireverzibilna elektroporacija predstavlja alternativo uveljavljenim termičnim ablacijskim metodam, saj mehanizem uničevanja celic ni pogojen z dvigom temperature. Zaradi ne-termičnega načina delovanja se zaenkrat uporablja predvsem v primerih, kjer uporaba termične ablacije ni mogoča zaradi nevarnosti poškodovanja bližnjih občutljivih anatomskih struktur ali kjer je učinkovitost ablacije zmanjšana zaradi odvajanja toplote (t. i. heat sink učinek). Trenutno se ireverzibilna elektroporacija v medicini uporablja predvsem za odstranjevanje globlje ležečih tumorjev, na primer v jetrih, prostati in ledvicah. V zadnjih letih je veliko zanimanja vzbudila tudi uporaba v srcu, in sicer za zdravljenje različnih motenj srčnega ritma. Ker je ablacija z ireverzibilno elektroporacijo relativno nova tehnologija, še vedno ni vzpostavljenih standardnih protokolov zdravljenja in postopkov načrtovanja zdravljenja. Numerične metode so nepogrešljivo orodje pri preučevanju fenomena elektroporacije in pri pripravi bolnikom prilagojenih načrtov zdravljenja. Prispevek obsega kratek pregled dosedanje uporabe ireverzibilne elektroporacije v kliničnem okolju, povzema prednosti in osvetljuje glavne izzive pri vpeljavi te obetavne ablacijske metode v klinično prakso.

10.6016/zdravvestn.2954

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Electrodes and Electric Field Distribution in Clinical Practice

Springer eBooks (2021)

Helena Cindrič Bor Kos Damijan Miklavčič

Electrochemotherapy

Irreversible Electroporation

Biological tissue

10.1007/978-3-030-80668-2_2

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Treatment Planning for Electrochemotherapy of Spinal Metastases

IFMBE proceedings (2024)

Helena Cindrič Damijan Miklavčič Bor Kos

Electrochemotherapy

Medical treatment

10.1007/978-3-031-49068-2_5

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Numerical mesoscale tissue model of electrochemotherapy in liver based on histological findings

Scientific Reports (2022)

Helena Cindrič Gorana Gašljević Ibrahim Edhemović Erik Brecelj Jan Žmuc

Abstract Electrochemotherapy (ECT) and irreversible electroporation (IRE) are being investigated for treatment of hepatic tumours. The liver is a highly heterogeneous organ, permeated with a network of macro- and microvasculature, biliary tracts and connective tissue. The success of ECT and IRE depends on sufficient electric field established in whole target tissue; therefore, tissue heterogeneity may affect the treatment outcome. In this study, we investigate electroporation in the liver using a numerical mesoscale tissue model. We numerically reconstructed four ECT experiments in healthy porcine liver and computed the electric field distribution using our treatment planning framework. We compared the computed results with histopathological changes identified on microscopic images after treatment. The mean electric field threshold that best fitted the zone of coagulation necrosis was 1225 V/cm, while the mean threshold that best fitted the zone of partially damaged liver parenchyma attributed to IRE was 805 V/cm. We evaluated how the liver macro- and microstructures affect the electric field distribution. Our results show that the liver microstructure does not significantly affect the electric field distribution on the level needed for treatment planning. However, major hepatic vessels and portal spaces significantly affect the electric field distribution, and should be considered when planning treatments.

Electrochemotherapy

Irreversible Electroporation

Liver tissue

10.1038/s41598-022-10426-2

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Citations (8)