On the Foundations of Plasma Electromagnetic Field Therapy
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Glioblastoma multiforme (GBM) is one of the most lethal forms of cancer, with a mediansurvival of 15 months despite extensive developments in modern approaches to treatment. Non-ionizing electromagnetic field therapies represent an emerging treatment paradigm, first clinically shown by Tumor Treating Fields (TTFields), demonstrating improved overall survival in clinical trials. The use of electromagnetic fields generated by plasma, coined Plasma Electromagnetic Field Therapy (PFT), has shown promise as a novel non-ionizing field-based therapy in the treatment of GBM. However, the systematic application of PFT requires quantitative dosimetry tools that relate physical exposure to biological outcome. This dissertation establishes the scientific foundations for plasma electromagnetic field therapy (PFT) for non-ionizing cancer treatment. The plasma discharge tube (PDT) delivers broadband electromagnetic fields in the kilohertz to gigahertz frequencies range without direct plasma-tissue contact. This work includes three novel contributions to the field, demonstrating a translational pathway from computational modeling to biological validation to treatment optimization. First, a broadband dosimetry framework using hybrid electroquasistatic and radiofrequency (EQS/RF) methods is developed for computing electromagnetic exposure in patient specific head anatomy. The Field-Intensity Exposure Index (FIEI) is introduced as the dosimetric quantity derived from field magnitude. Multi-source optimization demonstrates that increasing the number of PDT sources improves tumor coverage with diminishing returns beyond four sources. Second, in vitro validation establishes that delivered dose (FIEI integrated over exposure time) predicts biological response. Dose-response experiments using glioblastoma cells vi demonstrate a monotonic relationship between delivered dose and cytotoxicity under nonthermal conditions, validating the computational exposure metric with measured biological outcome. Finally, in vitro experiments with immortalized healthy glial cells demonstrate that this dose delivered is selective for cancer cells while leaving healthy cells unharmed. Third, multi-source synergy is demonstrated through dual-PDT configurations. Spatial mapping of cell death under dual-device exposure shows greater than expected cell death. In phase operation produces supra-additive cytotoxic enhancement, with a combination index below unity (CI <1) and intracellular reactive oxygen species correlating with enhanced cell death. These results validate that electromagnetic field superposition translates to biological outcome. These contributions establish PFT as a controllable therapeutic system with validated dosimetry. The computational, experimental, and optimization methods developed here provide the foundation for further studies, treatment planning and eventual clinical translation of plasma electromagnetic field therapy in neuro-oncology. vii
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