A Numerical Investigation of the Electric and Thermal Cell Kill Distributions in Electroporation-Based Therapies in Tissue

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dc.contributor.authorGarcia, Paulo A.en
dc.contributor.authorDavalos, Rafael V.en
dc.contributor.authorMiklavčič, Damijanen
dc.contributor.departmentSchool of Biomedical Engineering and Sciencesen
dc.date.accessioned2016-11-04T18:35:50Zen
dc.date.available2016-11-04T18:35:50Zen
dc.date.issued2014-08-12en
dc.description.abstractElectroporation-based therapies are powerful biotechnological tools for enhancing the delivery of exogeneous agents or killing tissue with pulsed electric fields (PEFs). Electrochemotherapy (ECT) and gene therapy based on gene electrotransfer (EGT) both use reversible electroporation to deliver chemotherapeutics or plasmid DNA into cells, respectively. In both ECT and EGT, the goal is to permeabilize the cell membrane while maintaining high cell viability in order to facilitate drug or gene transport into the cell cytoplasm and induce a therapeutic response. Irreversible electroporation (IRE) results in cell kill due to exposure to PEFs without drugs and is under clinical evaluation for treating otherwise unresectable tumors. These PEF therapies rely mainly on the electric field distributions and do not require changes in tissue temperature for their effectiveness. However, in immediate vicinity of the electrodes the treatment may results in cell kill due to thermal damage because of the inhomogeneous electric field distribution and high current density during the electroporation-based therapies. Therefore, the main objective of this numerical study is to evaluate the influence of pulse number and electrical conductivity in the predicted cell kill zone due to irreversible electroporation and thermal damage. Specifically, we simulated a typical IRE protocol that employs ninety 100-ms PEFs. Our results confirm that it is possible to achieve predominant cell kill due to electroporation if the PEF parameters are chosen carefully. However, if either the pulse number and/or the tissue conductivity are too high, there is also potential to achieve cell kill due to thermal damage in the immediate vicinity of the electrodes. Therefore, it is critical for physicians to be mindful of placement of electrodes with respect to critical tissue structures and treatment parameters in order to maintain the non-thermal benefits of electroporation and prevent unnecessary damage to surrounding healthy tissue, critical vascular structures, and/or adjacent organs.en
dc.description.versionPublished versionen
dc.format.extent? - ? (12) page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0103083en
dc.identifier.issn1932-6203en
dc.identifier.issue8en
dc.identifier.urihttp://hdl.handle.net/10919/73378en
dc.identifier.volume9en
dc.language.isoenen
dc.publisherPLOSen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000341230400011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectpercutaneous irreversible electroporationen
dc.subjectin-vivoen
dc.subjectpancreatic adenocarcinomaen
dc.subjectfield distributionen
dc.subjecttumor ablationen
dc.subjectelectrochemotherapyen
dc.subjectdamageen
dc.subjectsafetyen
dc.subjectmetastasesen
dc.subjectmembraneen
dc.titleA Numerical Investigation of the Electric and Thermal Cell Kill Distributions in Electroporation-Based Therapies in Tissueen
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Engineeringen
pubs.organisational-group/Virginia Tech/Engineering/Biomedical Engineering and Mechanicsen
pubs.organisational-group/Virginia Tech/Engineering/COE T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen

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