Estimation of Irreversible Electroporation (IRE) Electric Field Threshold (EFT), Area and associated Adiabatic Heating (AH) dependent on Pulsed Electric Field (PEF) waveform parameters

PFA Calculator Program

Instructions

  1. For details on how to use the hiPSC-CMs PFA Tool, read the Context of Use (CoU),which includes limitations of use.
  2. Insert the Pulsed Field Ablation (PFA) input parameters in the “PFA input parameters” table. Hover the information icons next to each section header for parameters definition and range of use. Check the changes you make to the “PFA input parameters” table in the waveform parameter interactive visual.
  3. Read the outputs in the “Program outputs” table to obtain the estimated lethal Electric Field Threshold (EFT), Absorbed Dose (AD), and Adiabatic Heating (AH) produced by the set of input parameter selected.
  4. For an estimate of the cell death area due to irreversible electroporation (IRE), insert the phase volage, $V_p$, in “Electric field distribution and cell-death area estimation” section. The electric field map will change accordingly showing the estimated cell death area for the set of pulse parameter selected and the specific electrode geometry used in this tool.

PFA input parameters

No. of Pulsesinfo Number of biphasic pulses in a train (50-400).
Phase durationinfo Duration of one phase in $[\mu s]$ composing the biphasic pulse $(0.2-10 \mu s)$. [$\mu s$]
PRFinfo Pulse Repetition Frequency in $[kHz]$: inverse of the time between the beginning of two consecutive pulses $(2-200 kHz)$. [$kHz$]
Interphase durationinfo Time between the two phases with opposing polarities in a single pulse $(=1 \mu s)$. [$\mu s$]
Densityinfo Mass density of the sample under test measured in $[g/cm^3]$. Use values from your experimental settings. If measurements are not available consider using literature, e.g, IT'IS density database. [$g/cm^3$]
Electrical Conductivityinfo Electrical conductivity of the sample under test measured in $[mS/cm]$. Use values from your experimental settings. If measurements are not available consider using literature, e.g. the dialectric properties database from IT'IS [$mS/cm$]

Ideal waveform parameter description and interactive visual representation

The schematic above, graphically displays how the parameters of a train of biphasic pulses are defined.

Program outputs

Lethal EFTinfo Lethal Electric Field Threshold estimated from in vitro experiments on hiPSC-CMs measured in $[kV/cm]$. [$kV/cm$]
ADinfo Absorbed Dose at the lethal EFT, measured in $[mJ/g]$, computed using the analytical Eq (1) presented in the CoU. [$mJ/g$]
AHinfo Adiabatic Heating at the lethal EFT, measured in $[C]$, computed using the analytical Eq (2) presented in the CoU. [$C$]

Electric field distribution and cell-death area estimation

Here, we have used the estimated lethal EFTs from this program, and combined the results with numerical simulations of the electric field, to estimate the cell-death area as an examplar.

Input: $V_p$info Input phase amplitude measured in [$V$] (100-1000 V, in increments of 10 V. $[V]$
Output: Est. cell death areainfo Esitmated cell death area based on the calculated lethal EFTs measured in $mm^2$. The min and max value are calculated based on the isolines obtained using the max and min value of lethal EFT, respectively. $[mm^2]$
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0 14.622 [kV/cm]

The map above displays the norm of the electric field in grayscale. The predicted cell-death region is highlighted in red, green, and blue, based on the estimated lethal EFT and the stregth of the electric field at the same point.