Physical electrode and mesh visualization for the extremely fine setting used in the numerical modeling software.

<p>Photograph of the physical bipolar electrode (left) and the electrode domain (right) geometry with the corresponding mesh employed in the computational modeling of the bipolar probe used in irreversible electroporation of liver tissue. The points P1, P2, and P3 depict the arbitrary locations at which the temperature was evaluated to determine the length required for thermal equilibration post-treatment.</p

Statistical model of the probability of cell kill due to pulse number in irreversible electroporation procedures.

<p>The results demonstrate that cell kill due to irreversible electroporation is a function of electric field strength and pulse number as depicted in the 2D contour plot. Note: The data for these plots was adapted from Golberg <i>et al.</i> and demonstrate that there is a minimum electric field and pulse number needed to achieve a 99.9% probability of cell kill due to electroporation <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103083#pone.0103083-Golberg1" target="_blank">[43]</a>.</p

Effect of pulse number on probability of electric damage during irreversible electroporation in liver tissue.

<p>Percentage cell kill due to electroporation after A) thirty, B) fifty, C) seventy, and D) ninety 100-µs pulses using a bipolar probe with an applied voltage of 3000 V. The solid isocontours represents the 50%, 90%, and 99.9% levels from the statistical model of cell kill due to irreversible electroporation, respectively.</p

Electrical conductivity response of liver tissue during irreversible electroporation.

<p>Numerical simulation of the A) electric field and C) electric conductivity distributions during irreversible electroporation procedures with a bipolar probe and an applied voltage of 3000 V. These results employ the B) non-linear electric field dependent liver tissue properties that result immediately after the end of each electroporation pulse and was scaled by 1.25×, 1.50×, and 1.75× in order to study potential organ-to-organ variability (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103083#pone-0103083-t002" target="_blank"><b>Table 2</b></a>).</p

Volumes of cell kill due to irreversible electroporation and thermal damage in liver tissue.

<p>Panel A displays the computed volumes of cell kill due to electroporation and thermal damage for each of the four baseline electrical conductivities investigated. Panels B shows the curves quantifying the ratio of cell kill due to thermal damage and electroporation as a function of conductivity as well. The results in panels A and B were computed during and after the delivery of a ninety 100-µs pulse electroporation protocol with an applied voltage of 3000 V at a pulse repetition frequency of 1 Hz.</p

Probability of cell kill due the cumulative effects of electroporation and thermal damage.

<p>Cell kill due to A) electroporation only, B) thermal damage only, and C) combined damage effects 10 minutes after the completion of the ninety 100-µs pulses delivered at a pulse repetition frequency of 1 Hz. Note: The solid black curves correspond to the 50%, 90%, and 99.9% cell kill isocontours.</p

Effect of pulse number on probability of thermal damage during irreversible electroporation in liver tissue.

<p>Percentage cell kill due to thermal damage after A) thirty, B) fifty, C) seventy, and D) ninety 100-µs pulses using a bipolar probe with an applied voltage of 3000 V. The solid isocontours represents the 50%, 90%, and 99.9% levels from the statistical model of cell kill due to thermal damage, respectively.</p

7.0-T Magnetic Resonance Imaging Characterization of Acute Blood-Brain-Barrier Disruption Achieved with Intracranial Irreversible Electroporation

<div><p>The blood-brain-barrier (BBB) presents a significant obstacle to the delivery of systemically administered chemotherapeutics for the treatment of brain cancer. Irreversible electroporation (IRE) is an emerging technology that uses pulsed electric fields for the non-thermal ablation of tumors. We hypothesized that there is a minimal electric field at which BBB disruption occurs surrounding an IRE-induced zone of ablation and that this transient response can be measured using gadolinium (Gd) uptake as a surrogate marker for BBB disruption. The study was performed in a Good Laboratory Practices (GLP) compliant facility and had Institutional Animal Care and Use Committee (IACUC) approval. IRE ablations were performed <em>in vivo</em> in normal rat brain (n = 21) with 1-mm electrodes (0.45 mm diameter) separated by an edge-to-edge distance of 4 mm. We used an ECM830 pulse generator to deliver ninety 50-μs pulse treatments (0, 200, 400, 600, 800, and 1000 V/cm) at 1 Hz. The effects of applied electric fields and timing of Gd administration (−5, +5, +15, and +30 min) was assessed by systematically characterizing IRE-induced regions of cell death and BBB disruption with 7.0-T magnetic resonance imaging (MRI) and histopathologic evaluations. Statistical analysis on the effect of applied electric field and Gd timing was conducted via Fit of Least Squares with α = 0.05 and linear regression analysis. The focal nature of IRE treatment was confirmed with 3D MRI reconstructions with linear correlations between volume of ablation and electric field. Our results also demonstrated that IRE is an ablation technique that kills brain tissue in a focal manner depicted by MRI (n = 16) and transiently disrupts the BBB adjacent to the ablated area in a voltage-dependent manner as seen with Evan's Blue (n = 5) and Gd administration.</p> </div

Morphologic characteristics of IRE-induced BBB disruption on 7.0-T MRI and Evan's Blue brain sections.

<p>The zones of ablation were achieved with ninety 50-μs pulses at a rate of one pulse per second. The Gadolinium (Gd) and Evan's Blue dyes were administered IP 5 minutes before the delivery of the pulses. The positive correlation between the applied voltage-to-distance ratios and the extent of BBB disruption induced by IRE is indicated by the uniformly contrast-enhancing zones of ablation on the T1W+Gd MR images and corresponding Evan's Blue brain slices. IRE-induced zones of ablation are sharply demarcated from the surrounding brain parenchyma. Linear hypointensities in the center of the zones of ablation, corresponding to the electrode insertions, are evident in the MR images from the 600, 800, and 1000 V/cm treatments.</p

Pulse parameters and Evan's Blue/Gd administration schedule used in IRE study.

†<p> <b> =  Evan's Blue (n = 5); *  =  Gadolinium (n = 16) (Magnevist®). A separate animal was used to assess each time point and electric field (n = 21).</b></p