Experimental characterization of intrapulse tissue conductivity changes for electroporation

Abstract

Cells exposed to short electric pulses experience a change in their transmembrane potential, which can lead to increased membrane permeability of the cell. When the energy of the pulses surpasses a threshold, the cell dies in a non-thermal manner known as irreversible electroporation (IRE). IRE has shown promise in the focal ablation of pathologic tissues. Its non-thermal mechanism spares sensitive structures and facilitates rapid lesion resolution. IRE effects depend on the electric field distribution, which can be predicted with numerical modeling. When the cells become permeabilized, the bulk tissue properties change, affecting this distribution. For IRE to become a reliable and successful treatment of diseased tissues, robust predictive treatment planning methods must be developed. It is vital to understand the changes in tissue properties undergoing the electric pulses to improve numerical models and predict treatment volumes. We report on the experimental characterization of these changes for kidney tissue. Tissue samples were pulsed between plate electrodes while intrapulse voltage and current data were measured to determine the conductivity of the tissue during the pulse. Conductivity was then established as a function of the electric field to which the tissue is exposed. This conductivity curve was used in a numerical model to demonstrate the impact of accounting for these changes when modeling electric field distributions to develop treatment plans.

Irreversible Electroporation: Treatment Effect is Susceptible to Local Environment and Tissue Properties

“…For the kidney, Neal et al noted (11) that electrical current values reached a plateau; whereas, we observed a decrease in current during the course of IRE treatment of the kidney. This discrepancy may be attributed to the difference in study design including our use of more clinically relevant in-vivo tissue with multiple repetitive IRE pulses compared with their treatment of ex-vivo tissue with a single IRE pulse.…”

“…This predictability, compared with that of radiofrequency ablation, has been attributed, at least in part, to the lack of perfusionmediated tissue cooling. Yet, as early studies of radiofrequency ablation have shown (10), tissue characteristics such as electrical conductivity may also influence IRE application, with effects on ablation shape and size that have not been completely characterized (11,12). Thus, because IRE is now being applied experimentally and clinically in a wide range of tissue including the kidney (13,14), pancreas (3,4), muscle, and soft tissue Implications for Patient Care n Use of IRE to ablate tumors in different organs may result in different ablation zone sizes for a given set of parameters based on tissue-specific characteristics.…”

Induction of rapid, reproducible hepatic ablations using next-generation, high frequency irreversible electroporation (H-FIRE) in vivo

“…In terms of electrode configuration, increasing number of electrodes, electrode exposure, and electrode separation should all result in larger ablation volumes, provided the optimal settings characterized in this study are implemented and the voltage-separation ratio is not reduced. [24][25][26] Other possibilities for maximizing ablation volume using H-FIRE, such as the number of cycles or number of bursts, requires further study, but could result in thermal effects if not performed correctly. 24 In addition to physical limitations, using multiple [2][3][4][5][6] electrode arrangements raises other clinical considerations.…”

“…[24][25][26] Other possibilities for maximizing ablation volume using H-FIRE, such as the number of cycles or number of bursts, requires further study, but could result in thermal effects if not performed correctly. 24 In addition to physical limitations, using multiple [2][3][4][5][6] electrode arrangements raises other clinical considerations. A notable disadvantage of current IRE technology is increased operative time and complexity associated with placing multiple electrodes, particularly if the tumor is located near a critical structure or deep within the parenchyma, and the need to do so using an open approach.…”

“…That is, as cells within the electrical field undergo IRE, tissue conductivity changes and affects the flow of electrical current, and the presence of connective tissue and cell-cell interactions can further distort electric field distribution. 24 As a result, ablation geometries that differ from predicted models can arise. 16 By operating at higher frequencies, H-FIRE minimizes the effect of changing conductivities from electroporation and undermines electrical heterogeneities of surrounding tissue to dramatically increase ablation predictability.…”