Browsing by Author "Arena, Christopher B."

Now showing 1 - 20 of 21
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    Bursts of Bipolar Microsecond Pulses Inhibit Tumor Growth
    Sano, Michael B.; Arena, Christopher B.; Bittleman, Katelyn Rose; DeWitt, Matthew R.; Cho, Hyung J.; Szot, Cchristopher S.; Saur, Dieter; Cissell, James M.; Robertson, John L.; Lee, Yong Woo; Davalos, Rafael V. (Nature Publishing Group, 2015-10-13)
    Irreversible electroporation (IRE) is an emerging focal therapy which is demonstrating utility in the treatment of unresectable tumors where thermal ablation techniques are contraindicated. IRE uses ultra-short duration, high-intensity monopolar pulsed electric fields to permanently disrupt cell membranes within a well-defined volume. Though preliminary clinical results for IRE are promising, implementing IRE can be challenging due to the heterogeneous nature of tumor tissue and the unintended induction of muscle contractions. High-frequency IRE (H-FIRE), a new treatment modality which replaces the monopolar IRE pulses with a burst of bipolar pulses, has the potential to resolve these clinical challenges. We explored the pulse-duration space between 250 ns and 100 μs and determined the lethal electric field intensity for specific H-FIRE protocols using a 3D tumor mimic. Murine tumors were exposed to 120 bursts, each energized for 100 μs, containing individual pulses 1, 2, or 5 μs in duration. Tumor growth was significantly inhibited and all protocols were able to achieve complete regressions. The H-FIRE protocol substantially reduces muscle contractions and the therapy can be delivered without the need for a neuromuscular blockade. This work shows the potential for H-FIRE to be used as a focal therapy and merits its investigation in larger pre-clinical models.
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    Deactivation of Ascaris suum eggs using electroporation and sequential inactivation with chemical disinfection
    Niven, C.; Parker, C. B.; Wolter, S. D.; Dryzer, M. H.; Arena, Christopher B.; Stoner, B. R.; Ngaboyamahina, E. (2020-09)
    Electroporation has been evaluated as a potential backend wastewater treatment for deactivation ofAscaris suumeggs in buffer solution. Initial results indicate that eggshell permeability is affected by the pulse train electric field strength and duration. Coupling electroporation with chemical exposure, using low concentrations of commercially available disinfectants, allows oxidizing agents to pass through the complex strata of theA. suumeggshell, specifically reaching the innermost embryonic environment, which leads to successful deactivation compared to either method used separately. The aim of this work is to identify and develop an alternative technique that efficiently inactivates helminth eggs present in wastewater.
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    Devices, systems, and methods for real-time monitoring of electrophysical effects during tissue treatment
    (United States Patent and Trademark Office, 2020-06-30)
    Provided herein are devices, systems, and methods for monitoring lesion or treated area in a tissue during focal ablation or cell membrane disruption therapy. Provided herein are embodiments of an electrical conductivity sensor having an impedance sensor, where the impedance sensor can be configured to measure a low-frequency and a high-frequency impedance and a substrate, where the impedance sensor is coupled to the substrate. The substrate can be flexible. In embodiments, the impedance sensor can contain two or more electrical conductors. The electrical conductors can be in a bipolar configuration. The electrical conductors can be in a tetrapolar configuration. In embodiments, the electrical conductivity sensor can have two impedance sensors that can be coupled to the substrate such that they are orthogonal to each other.
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    Electropermeabilization of nematode eggs for parasite deactivation
    Dryzer, M. H.; Niven, C.; Wolter, S. D.; Arena, Christopher B.; Ngaboyamahina, E.; Parker, C. B.; Stoner, B. R. (2019-03)
    The eggs of parasitic helminth worms are incredibly resilient - possessing the ability to survive changing environmental factors and exposure to chemical treatments - which has restricted the efficacy of wastewater sanitation. This research reports on the effectiveness of electroporation to permeabilize ova of Caenorhabditis elegans (C. elegans), a helminth surrogate, for parasite deactivation. This technique utilizes electric pulses to increase cell membrane permeability in its conventional application, but herein is used to open pores in nonparasitic nematode eggshells - the first report of such an application to the best knowledge of the authors. A parametric evaluation of electric field strength and total electroporation duration of eggs and worms in phosphate-buffered saline was performed using a 1 Hz pulse train of 0.01% duty cycle. The extent of pore formation was determined using a fluorescent label, propidium iodide, targeting C. elegans embryonic DNA. The results of this research demonstrate that electroporation increases eggshell permeability. This treatment, coupled with existing methods of electrochemical disinfection, could improve upon current attempts at the deactivation of helminth eggs. We discuss electroporation treatment conditions and likely modification of the lipid-rich permeability barrier within the eggshell strata.
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    Folate Conjugated Cellulose Nanocrystals Potentiate Irreversible Electroporation-induced Cytotoxicity for the Selective Treatment of Cancer Cells
    Colacino, Katelyn R.; Arena, Christopher B.; Dong, Shuping; Roman, Maren; Davalos, Rafael V.; Lee, Yong Woo (Adenine Press, 2014-04-16)
    Cellulose nanocrystals are rod-shaped, crystalline nanoparticles that have shown prom- ise in a number of industrial applications for their unique chemical and physical properties. However, investigations of their abilities in the biomedical field are limited. The goal of this study is to show the potential use of folic acid-conjugated cellulose nanocrystals in the potentiation of irreversible electroporation-induced cell death in folate receptor (FR)-positive cancers. We optimized key pulse parameters including pulse duration, intensity, and incubation time with nanoparticles prior to electroporation. FR-positive cancer cells, KB and MDA-MB-468, were preincubated with cellulose nanocrystals (CNCs) conjugated with the targeting molecule folic acid (FA), 10 and 20 min respectively, prior to application of the optimized pulse electric field (PEF), 600 and 500 V/cm respectively. We have shown cellulose nanocrystals’ ability to potentiate a new technique for tumor ablation, irreversible electroporation. Pre-incubation with FA-conjugated CNCs (CNC-FA) has shown a significant increase in cytotoxicity induced by irreversible electroporation in FR-positive cancer cells, KB and MDA-MB-468. Non-targeted CNCs (CNC-COOH) did not potentiate IRE when preincubated at the same parameters as previously stated in these cell types. In addition, CNC-FA did not potentiate irreversible electroporation-induced cytotoxicity in a FR-negative cancer cell type, A549. Without changing irreversible electroporation parameters it is possible to increase the cytotoxic effect on FR-positive cancer cells by exploiting the specific binding of FA to the FR, while not causing further damage to FR-negative tissue.
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    High frequency electroporation for cancer therapy
    (United States Patent and Trademark Office, 2019-05-21)
    The present invention relates to the field of biomedical engineering and medical treatment of diseases and disorders. Methods, devices, and systems for in vivo treatment of cell proliferative disorders are provided. In embodiments, the methods comprise the delivery of high-frequency bursts of bipolar pulses to achieve the desired modality of cell death. More specifically, embodiments of the invention relate to a device and method for destroying aberrant cells, including tumor tissues, using high-frequency, bipolar electrical pulses having a burst width on the order of microseconds and duration of single polarity on the microsecond to nanosecond scale. In embodiments, the methods rely on conventional electroporation with adjuvant drugs or irreversible electroporation to cause cell death in treated tumors. The invention can be used to treat solid tumors, such as brain tumors.
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    High-frequency electroporation for cancer therapy
    (United States Patent and Trademark Office, 2019-10-22)
    The present invention relates to the field of biomedical engineering and medical treatment of diseases and disorders. Methods, devices, and systems for in vivo treatment of cell proliferative disorders are provided. In embodiments, the methods comprise the delivery of high-frequency bursts of bipolar pulses to achieve the desired modality of cell death. More specifically, embodiments of the invention relate to a device and method for destroying aberrant cells, including tumor tissues, using high-frequency, bipolar electrical pulses having a burst width on the order of microseconds and duration of single polarity on the microsecond to nanosecond scale. In embodiments, the methods rely on conventional electroporation with adjuvant drugs or irreversible electroporation to cause cell death in treated tumors. The invention can be used to treat solid tumors, such as brain tumors.
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    High-frequency irreversible electroporation (H-FIRE) for non-thermal ablation without muscle contraction
    Arena, Christopher B.; Sano, Michael B.; Rossmeisl, John H. Jr.; Caldwell, John L.; Garcia, Paulo A.; Rylander, M. Nichole; Davalos, Rafael V. (2011-11-21)
    Background Therapeutic irreversible electroporation (IRE) is an emerging technology for the non-thermal ablation of tumors. The technique involves delivering a series of unipolar electric pulses to permanently destabilize the plasma membrane of cancer cells through an increase in transmembrane potential, which leads to the development of a tissue lesion. Clinically, IRE requires the administration of paralytic agents to prevent muscle contractions during treatment that are associated with the delivery of electric pulses. This study shows that by applying high-frequency, bipolar bursts, muscle contractions can be eliminated during IRE without compromising the non-thermal mechanism of cell death. Methods A combination of analytical, numerical, and experimental techniques were performed to investigate high-frequency irreversible electroporation (H-FIRE). A theoretical model for determining transmembrane potential in response to arbitrary electric fields was used to identify optimal burst frequencies and amplitudes for in vivo treatments. A finite element model for predicting thermal damage based on the electric field distribution was used to design non-thermal protocols for in vivo experiments. H-FIRE was applied to the brain of rats, and muscle contractions were quantified via accelerometers placed at the cervicothoracic junction. MRI and histological evaluation was performed post-operatively to assess ablation. Results No visual or tactile evidence of muscle contraction was seen during H-FIRE at 250 kHz or 500 kHz, while all IRE protocols resulted in detectable muscle contractions at the cervicothoracic junction. H-FIRE produced ablative lesions in brain tissue that were characteristic in cellular morphology of non-thermal IRE treatments. Specifically, there was complete uniformity of tissue death within targeted areas, and a sharp transition zone was present between lesioned and normal brain. Conclusions H-FIRE is a feasible technique for non-thermal tissue ablation that eliminates muscle contractions seen in IRE treatments performed with unipolar electric pulses. Therefore, it has the potential to be performed clinically without the administration of paralytic agents.
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    High-Frequency Irreversible Electroporation for Intracranial Meningioma: A Feasibility Study in a Spontaneous Canine Tumor Model
    Latouche, Eduardo L.; Arena, Christopher B.; Ivey, Jill W.; Garcia, Paulo A.; Pancotto, Theresa E.; Pavlisko, Noah; Verbridge, Scott S.; Davalos, Rafael V.; Rossmeisl, John H. Jr. (Sage, 2018)
    High-frequency irreversible electroporation is a nonthermal method of tissue ablation that uses bursts of 0.5- to 2.0-microsecond bipolar electric pulses to permeabilize cell membranes and induce cell death. High-frequency irreversible electroporation has potential advantages for use in neurosurgery, including the ability to deliver pulses without inducing muscle contraction, inherent selectivity against malignant cells, and the capability of simultaneously opening the blood–brain barrier surrounding regions of ablation. Our objective was to determine whether high-frequency irreversible electroporation pulses capable of tumor ablation could be delivered to dogs with intracranial meningiomas. Three dogs with intracranial meningiomas were treated. Patient-specific treatment plans were generated using magnetic resonance imaging-based tissue segmentation, volumetric meshing, and finite element modeling. Following tumor biopsy, high-frequency irreversible electroporation pulses were stereotactically delivered in situ followed by tumor resection and morphologic and volumetric assessments of ablations. Clinical evaluations of treatment included pre- and posttreatment clinical, laboratory, and magnetic resonance imaging examinations and adverse event monitoring for 2 weeks posttreatment. High-frequency irreversible electroporation pulses were administered successfully in all patients. No adverse events directly attributable to high-frequency irreversible electroporation were observed. Individual ablations resulted in volumes of tumor necrosis ranging from 0.25 to 1.29 cm3. In one dog, nonuniform ablations were observed, with viable tumor cells remaining around foci of intratumoral mineralization. In conclusion, high-frequency irreversible electroporation pulses can be delivered to brain tumors, including areas adjacent to critical vasculature, and are capable of producing clinically relevant volumes of tumor ablation. Mineralization may complicate achievement of complete tumor ablation.
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    Improved Local and Systemic Anti-Tumor Efficacy for Irreversible Electroporation in Immunocompetent versus Immunodeficient Mice
    Neal, Robert E. II; Rossmeisl, John H. Jr.; Robertson, John L.; Arena, Christopher B.; Davis, Erica M.; Singh, Ravi N.; Stallings, Jonathan; Davalos, Rafael V. (PLOS, 2013-05-24)
    Irreversible electroporation (IRE) is a non-thermal focal ablation technique that uses a series of brief but intense electric pulses delivered into a targeted region of tissue, killing the cells by irrecoverably disrupting cellular membrane integrity. This study investigates if there is an improved local anti-tumor response in immunocompetent (IC) BALB/c versus immunodeficient (ID) nude mice, including the potential for a systemic protective effect against rechallenge. Subcutaneous murine renal carcinoma tumors were treated with an IRE pulsing protocol that used 60% of the predicted voltage required to invoke complete regressions in the ID mice. Tumors were followed for 34 days following treatment for 11 treated mice from each strain, and 7 controls from each strain. Mouse survival based on tumor burden and the progression-free disease period was substantially longer in the treated IC mice relative to the treated ID mice and sham controls for both strains. Treated IC mice were rechallenged with the same cell line 18 days after treatment, where growth of the second tumors was shown to be significantly reduced or prevented entirely. There was robust CD3+ cell infiltration in some treated BALB/C mice, with immunocytes focused at the transition between viable and dead tumor. There was no difference in the low immunocyte presence for untreated tumors, nude mice, and matrigel-only injections in both strains. These findings suggest IRE therapy may have greater therapeutic efficacy in immunocompetent patients than what has been suggested by immunodeficient models, and that IRE may invoke a systemic response beyond the targeted ablation region.
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    The inefficiency of open-loop fMRI experiments
    Norfleet, David George (Virginia Tech, 2023-06-29)
    The default mode network (DMN) is a highly cited neural network whose functional roles are not well understood. Until recently, event related fMRI experiments used to study the DMN could only be conducted in an open-loop format. The purpose of this study was to demonstrate the potential statistical advantages of real-time fMRI studies to conduct closed-loop experiments to directly test putative DMN functions. Using both fMRI simulations and large archival datasets, we demonstrate that open-loop designs are less statistically powerful than closed-loop experiments that can trigger stimuli at controlled levels of brain activity. When simulating event scheduling on resting state data, DMN levels were normally distributed, but the event timing proved to be ineffective in capturing the highest and lowest DMN values on average across subjects. Statistical differences in DMN levels collected by the Human Connectome Project-Aging (HCP-A) during a Go/NoGo task were also reported, along with the network's distributional effects across subjects. When examining DMN levels in 136 subjects more prone to commission errors the mean DMN levels were reported to be higher during and prior to incorrect NoGo responses. Exploring DMN levels in these same individuals reacting to a Go task also revealed differing measurement patterns when compared to all 711 subjects in the study. Additionally, the distribution of total DMN levels across all participants, as well as during a Go or NoGo trial, showed a shift in the mean towards deactivation. Furthermore, the peak at this location was greater and revealed that increased sampling occurred at the mean and under sampling at the tails. Overall, the cumulative findings in this study were successful in providing statistical arguments to support propositions for more powerful closed-loop experimentation in fMRI.
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    Integration of very short electric pulses for minimally to noninvasive electroporation
    (United States Patent and Trademark Office, 2015-01-06)
    The present invention provides methods, devices, and systems for in vivo treatment of cell proliferative disorders. The invention can be used to treat solid tumors, such as brain tumors. The methods rely on non-thermal irreversible electroporation (IRE) or supra-poration to cause cell death in treated tumors. In embodiments, the methods comprise the integration of ultra-short electric pulses, both temporally and spatially, to achieve the desired modality of cell death.
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    An Investigation for Large Volume, Focal Blood-Brain Barrier Disruption with High-Frequency Pulsed Electric Fields
    Lorenzo, Melvin F.; Campelo, Sabrina N.; Arroyo, Julio P.; Aycock, Kenneth N.; Hinckley, Jonathan; Arena, Christopher B.; Rossmeisl, John H. Jr.; Davalos, Rafael V. (MDPI, 2021-12-20)
    The treatment of CNS disorders suffers from the inability to deliver large therapeutic agents to the brain parenchyma due to protection from the blood-brain barrier (BBB). Herein, we investigated high-frequency pulsed electric field (HF-PEF) therapy of various pulse widths and interphase delays for BBB disruption while selectively minimizing cell ablation. Eighteen male Fisher rats underwent craniectomy procedures and two blunt-tipped electrodes were advanced into the brain for pulsing. BBB disruption was verified with contrast T1W MRI and pathologically with Evans blue dye. High-frequency irreversible electroporation cell death of healthy rodent astrocytes was investigated in vitro using a collagen hydrogel tissue mimic. Numerical analysis was conducted to determine the electric fields in which BBB disruption and cell ablation occur. Differences between the BBB disruption and ablation thresholds for each waveform are as follows: 2-2-2 μs (1028 V/cm), 5-2-5 μs (721 V/cm), 10-1-10 μs (547 V/cm), 2-5-2 μs (1043 V/cm), and 5-5-5 μs (751 V/cm). These data suggest that HF-PEFs can be fine-tuned to modulate the extent of cell death while maximizing peri-ablative BBB disruption. Furthermore, numerical modeling elucidated the diffuse field gradients of a single-needle grounding pad configuration to favor large-volume BBB disruption, while the monopolar probe configuration is more amenable to ablation and reversible electroporation effects.
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    Irreversible electroporation using nanoparticles
    (United States Patent and Trademark Office, 2013-06-18)
    The present invention provides methods, devices, and systems for in vivo treatment of cell proliferative disorders. The invention can be used to treat solid tumors, such as brain tumors. The methods rely on non-thermal irreversible electroporation (IRE) to cause cell death in treated tumors. In embodiments, the methods comprise the use of high aspect ratio nanoparticles with or without modified surface chemistry.
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    Irreversible electroporation using nanoparticles
    (United States Patent and Trademark Office, 2014-08-26)
    The present invention provides methods, devices, and systems for in vivo treatment of cell proliferative disorders. The invention can be used to treat solid tumors, such as brain tumors. The methods rely on non-thermal irreversible electroporation (IRE) to cause cell death in treated tumors. In embodiments, the methods comprise the use of high aspect ratio nanoparticles with or without modified surface chemistry.
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    Maximizing Local Access to Therapeutic Deliveries in Glioblastoma. Part III: Irreversible Electroporation and High-Frequency Irreversible Electroporation for the Eradication of Glioblastoma
    Lorenzo, Melvin F.; Arena, Christopher B.; Davalos, Rafael V. (2017)
    Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. Approximately 9180 primary GBM tumors are diagnosed in the United States each year, in which median survival is up to 16 months. GBM eludes and resists typical cancer treatments due to the presence of infiltrative cells beyond the solid tumor margin, heterogeneity within the tumor microenvironment, and protection from the blood-brain barrier. Conventional treatments for GBM, such as surgical resection, radiotherapy, and chemotherapy, have shown limited efficacy; therefore, alternate treatments are needed. Tumor chemoresistance and its proximity to critical structures make GBM a prime theoretical candidate for nonthermal ablation with irreversible electroporation (IRE) and high-frequency IRE (H-FIRE). IRE and H-FIRE are treatment modalities that utilize pulsed electric fields to permeabilize the cell membrane. Once the electric field magnitude exceeds a tissue-specific lethal threshold, cell death occurs. Benefits of IRE and H-FIRE therapy include, but are not limited to, the elimination of cytotoxic effects, sharp delineation from treated tissue and spared tissue, a nonthermal mechanism of ablation, and sparing of nerves and major blood vessels. Preclinical studies have confirmed the safety and efficacy of IRE and H-FIRE within their experimental scope. In this chapter, studies will be collected and information extrapolated to provide possible treatment regimens for use in high-grade gliomas, specifically in GBM.
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    Mitigation of impedance changes due to electroporation therapy using bursts of high-frequency bipolar pulses
    Bhonsle, Suyashree P.; Arena, Christopher B.; Sweeney, Daniel C.; Davalos, Rafael V. (2015-08-27)
    Background For electroporation-based therapies, accurate modeling of the electric field distribution within the target tissue is important for predicting the treatment volume. In response to conventional, unipolar pulses, the electrical impedance of a tissue varies as a function of the local electric field, leading to a redistribution of the field. These dynamic impedance changes, which depend on the tissue type and the applied electric field, need to be quantified a priori, making mathematical modeling complicated. Here, it is shown that the impedance changes during high-frequency, bipolar electroporation therapy are reduced, and the electric field distribution can be approximated using the analytical solution to Laplace's equation that is valid for a homogeneous medium of constant conductivity. Methods Two methods were used to examine the agreement between the analytical solution to Laplace's equation and the electric fields generated by 100 µs unipolar pulses and bursts of 1 µs bipolar pulses. First, pulses were applied to potato tuber tissue while an infrared camera was used to monitor the temperature distribution in real-time as a corollary to the electric field distribution. The analytical solution was overlaid on the thermal images for a qualitative assessment of the electric fields. Second, potato ablations were performed and the lesion size was measured along the x- and y-axes. These values were compared to the analytical solution to quantify its ability to predict treatment outcomes. To analyze the dynamic impedance changes due to electroporation at different frequencies, electrical impedance measurements (1 Hz to 1 MHz) were made before and after the treatment of potato tissue. Results For high-frequency bipolar burst treatment, the thermal images closely mirrored the constant electric field contours. The potato tissue lesions differed from the analytical solution by 39.7 ± 1.3 % (x-axis) and 6.87 ± 6.26 % (y-axis) for conventional unipolar pulses, and 15.46 ± 1.37 % (x-axis) and 3.63 ± 5.9 % (y-axis) for high- frequency bipolar pulses. Conclusions The electric field distributions due to high-frequency, bipolar electroporation pulses can be closely approximated with the homogeneous analytical solution. This paves way for modeling fields without prior characterization of non-linear tissue properties, and thereby simplifying electroporation procedures.
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    Selective modulation of intracellular effects of cells using pulsed electric fields
    (United States Patent and Trademark Office, 2019-11-12)
    A system and method for selectively treating aberrant cells such as cancer cells through administration of a train of electrical pulses is described. The pulse length and delay between successive pulses is optimized to produce effects on intracellular membrane potentials. Therapies based on the system and method produce two treatment zones: an ablation zone surrounding the electrodes within which aberrant cells are non-selectively killed and a selective treatment zone surrounding the ablation zone within which target cells are selectively killed through effects on intracellular membrane potentials. As a result, infiltrating tumor cells within a tumor margin can be effectively treated while sparing healthy tissue. The system and method are useful for treating various cancers in which solid tumors form and have a chance of recurrence from microscopic disease surrounding the tumor.
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    System and method for estimating tissue heating of a target ablation zone for electrical-energy based therapies
    (United States Patent and Trademark Office, 2018-11-06)
    Systems and methods are provided for modeling and for providing a graphical representation of tissue heating and electric field distributions for medical treatment devices that apply electrical treatment energy through one or a plurality of electrodes. In embodiments, methods comprise: providing one or more parameters of a treatment protocol for delivering one or more electrical pulses to tissue through a plurality of electrodes; modeling electric and heat distribution in the tissue based on the parameters; and displaying a graphical representation of the modeled electric and heat distribution. In another embodiment, a treatment planning module is adapted to generate an estimated target ablation zone based on a combination of one or more parameters for an irreversible electroporation protocol and one or more tissue-specific conductivity parameters.
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    A Three-Dimensional in Vitro Tumor Platform for Modeling Therapeutic Irreversible Electroporation
    Arena, Christopher B.; Szot, Cchristopher S.; Garcia, Paulo A.; Rylander, M. Nichole; Davalos, Rafael V. (Cell Press, 2012-06-01)
    Irreversible electroporation (IRE) is emerging as a powerful tool for tumor ablation that utilizes pulsed electric fields to destabilize the plasma membrane of cancer cells past the point of recovery. The ablated region is dictated primarily by the electric field distribution in the tissue, which forms the basis of current treatment planning algorithms. To generate data for refinement of these algorithms, there is a need to develop a physiologically accurate and reproducible platform on which to study IRE in vitro. Here, IRE was performed on a 3D in vitro tumor model consisting of cancer cells cultured within dense collagen I hydrogels, which have been shown to acquire phenotypes and respond to therapeutic stimuli in a manner analogous to that observed in in vivo pathological systems. Electrical and thermal fluctuations were monitored during treatment, and this information was incorporated into a numerical model for predicting the electric field distribution in the tumors. When correlated with Live/Dead staining of the tumors, an electric field threshold for cell death (500 V/cm) comparable to values reported in vivo was generated. In addition, submillimeter resolution was observed at the boundary between the treated and untreated regions, which is characteristic of in vivo IRE. Overall, these results illustrate the advantages of using 3D cancer cell culture models to improve IRE-treatment planning and facilitate widespread clinical use of the technology.