Predicting the electroporated tissue area trajectory in Electroporation-based protocol optimization

TL;DR

This paper introduces a novel method to predict the electroporated tissue area trajectory over time using a single measurement, simplifying protocol optimization in electroporation-based treatments.

Contribution

It presents a new nonlinear dynamic analysis approach that links the EP threshold trajectory to the tissue area trajectory, enabling predictions without measuring the threshold directly.

Findings

The EP threshold trajectory is the time gradient of the electric field.

The tissue area trajectory can be predicted from a single measurement.

The method explains the exponential decrease of EP threshold and logarithmic increase of tissue area.

Abstract

Electroporation (EP), the temporary or permanent permeabilization of the cell membrane induced by an electric field, is the basis of various applications in medicine and food processing. In EP-based protocol optimization in terms of pulse number, such as in electrochemotherapy (ECT), irreversible electroporation (IRE), and gene electrotransfer (GET), it is essential to reach an optimal dose-response, that is, the pulse dose that maximizes the electroporated tissue area while minimizing damage. Predicting the electroporated tissue area variation in time, i.e., its trajectory, requires measuring the EP threshold trajectory and understanding the interaction between both trajectories and the damaged tissue area trajectory. Here we introduce a new methodology, based on the analysis of the nonlinear dynamic interaction of the EP threshold and damaged tissue area trajectories, that shows that the EP threshold trajectory is the time gradient of the electric field. This allows predicting the electroporated area trajectory with a single electroporated area measurement at the last pulse, thus avoiding the need to measure the EP threshold trajectory, a rather cumbersome task. Also, it makes it possible to explain at the macroscopic level why the EP threshold trajectory has an approximate exponential time decrease while the EP threshold isoline trajectory, aka the electroporated tissue area trajectory, has an approximate logarithmic time increase. Further, it permits predicting an optimal dose response in terms of pulse number in an EP-based protocol, with a single electroporated tissue area measurement. Examples of its application to an in vitro vegetal model, and to an in vivo skinfold chamber shed new light on the nonlinear dynamic behavior of electroporated tissue area, EP threshold, and damaged tissue area trajectories, paving the way for optimal treatment planning in EP-based protocols.