  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.
