This project included a completely multidisciplinary approach to give response to the different scientific questions presented in the proposal of the project.
During the project, purely engineering tasks were developed. An equipment for performing experiments was an electric field generator with a high flexibility for delivering arbitrary and high-frequency electric field waveforms was developed. As the equipment needed to be robust and safe for performing the subsequent experiments in proper safety conditions, the generator was developed with an external company expert in power electronics design. Additional to the electric field delivery system, an impedance sensing system was developed to be used in synchronization with the generator. Also, proper electrical isolation was provided to the system. A high speed temperature measuring system based on optical fibers was also integrated in the experimental setup to enable temperature recordings during electric field delivery.
Another important aspect covered during this project, was the development of numerical models for finite element simulations. These models enable to calculate the electric field distribution in the target tissue for any catheter topology and predict the shape and size of the lesion area created by Pulsed Field Ablation (PFA) therapies. Additionally, the models enabled to estimate the temperature gradients during treatments. The models were also used to compare PFA to the standard radiofrequency ablation technique. The numerical comparison of both techniques was published in a journal article (
https://www.nature.com/articles/s41598-022-20212-9(odnośnik otworzy się w nowym oknie)) and presented in international conferences. Also, in the framework of a collaboration with cardiologists from the Mayo Clinic in United States, numerical models based on MRI reconstructions of real animal cases were used to estimate the electric field lethal thresholds necessary to create damage to cardiac tissue. This was presented in a high-impact international medical conference (
https://doi.org/10.1093/eurheartj/ehac544.475(odnośnik otworzy się w nowym oknie)).
Regarding the biological experimentation performed along the project, different levels of complexity were implemented. First, in vitro experiments with cells in culture were used to establish the basic dependencies of different electric field waveform parameters (amplitude, frequency, number of applications) on efficacy. Subsequently, a complete study was performed in small animals (rats) with the goal of performing a first in vivo validation and optimization of the therapy previous to transferring the experiments to bigger animals. These studies demonstrated the strong dependency of PFA efficacy with the frequency of the applied waveform. The main results were published in a journal article in a relevant electrophysiology journal (
https://doi.org/10.1161/CIRCEP.122.010992(odnośnik otworzy się w nowym oknie)). At the final stage of the project, preclinical studies were performed in swine. The first study consisted in the validation of the PFA efficacy on the ventricular epicardium and a detailed characterization of the changes in the local electrograms produced as a consequence of the therapy both in reversible and irreversible electroporation areas. The results of this study could have important implications in the routine practice of the electrophysiologists using this ablation modality. The main results were published in a relevant electrophysiology journal (
https://doi.org/10.1161/CIRCEP.123.011914(odnośnik otworzy się w nowym oknie)). The second study consisted in a proof of concept of a novel idea which would use a new catheter design capable of injecting substances to cardiac tissue and applying PFA at the same time. The results of this proof of concept are being prepared for publication.
