An Investigation of Thermal Mitigation Strategies for Electroporation-Based Therapies
| Autor: | O'Brien, Timothy J. |
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| Rok vydání: | 2019 |
| Předmět: | |
| Druh dokumentu: | Dissertation |
| Popis: | Irreversible electroporation (IRE) is an energy directed focal ablation technique. This procedure typically involves the placement of two or more electrodes into, or around, a region of interest within the tissue and administering a sequence of short, intense, pulsed electric fields (PEFs). The application of these PEFs results in an increase in the transmembrane potential of all cells within the electric field above a critical value, destabilizing the lipid bilayer of the cellular membrane and increasing the cell-tissue permeability. For years, many have used this phenomenon to assist the transport of macromolecules typically unable to penetrate the cell membrane with the intent of avoiding cell necrosis or irreversible electroporation. More recently, however, irreversible electroporation has proven to be a successful alternative for the treatment of cancer. Proper tuning of the pulse parameters has allowed for a targeted treatment of localized tumors, and has shown immense value in the treatment of surgically inoperable tumors located near major blood vessels and nerves. While it is critical to ensure sufficient treatment of the target tissue, it can be equally vital to the treatment and patients overall outcome that the pulsing conditions are set to moderate the associated thermal effects with the electroporation of biological tissue. The development of thermal mitigation strategies for IRE treatment is the focus of this dissertation. Herein, the underlying theory and thermal considerations of tissue electroporation in various scenarios are described. Additionally, new thermal mitigation approaches with the intention of maintaining tissue temperature below a thermally damaging threshold, while also preserving or improving IRE lesion volume are detailed. Further, numerical models were developed and ex vivo tissue experiments performed using a perfused organ model to examine three thermal mitigation strategies in their ability to moderate temperature. Tests conducted using thermally mitigating treatment delivery on live tissue confirm the capacity to deliver more energy to the tissue at a thermally acceptable temperature, and provide the potential for a replete IRE lesion. Doctor of Philosophy Irreversible electroporation (IRE) is a minimally invasive therapy utilized to treat a variety of cancers. This procedure involves the delivery energy in the form of pulsed electric fields (PEFs) through two or more needle electrodes. These PEFs destabilize the cell membrane, increase the cell-tissue permeability, and ultimately induce cell death for any given cell within the targeted treatment region. Over the years, this treatment modality has shown a great deal of promise in the treatment of unresectable tumors in which the tumor is positioned near or around sensitive regions making the surgical removal of the tumor impossible and thermal ablation techniques limited in their ability to treat without irrevocably damaging the underlying tissue architecture and other critical surrounding structures. Thus, it can be vital to the treatment and patients overall outcome that the IRE therapy is set to moderate any associated thermal effects with the electroporation of biological tissue. However, the design of an electric field that simultaneously maps the entire region of interest for a single treatment and avoids undesirable thermal effects can be challenging when treating larger or irregularly shaped volumes of tissue. Thus, in this dissertation, we demonstrate various treatment delivery methods/ enhancements to reduce temperature rise during IRE therapy. The underlying theory of tissue electroporation and associated thermal considerations are described to provide a foundation and general context. Additionally, novel approaches to tissue electroporation therapy with the intention of maintaining tissue temperature below a thermally damaging threshold throughout treatment are detailed. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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