Electroporation is a phenomenon in which short high-voltage electric pulses are used to change the structural integrity of the cell membrane, thereby increasing membrane permeability. With appropriate choice of pulse parameters, the phenomenon can be reversible or irreversible. Both types of electroporation are used in various medical applications. Reversible electroporation is used in electrochemotherapy and gene electrotransfer, while irreversible electroporation is used for ablation of tumors and ablation in the heart to treat atrial fibrillation.
Numerical methods are an important tool for analyzing complex interactions in biological tissue during electroporation. Many aspects of the clinical applications of electroporation are still unresolved. Numerical modeling allows us to investigate new treatment approaches, test new electrode designs, and analyze different clinical scenarios for the feasibility and safety aspects. The use of numerical models also reduces the number of preclinical and clinical studies required to develop treatments based on electroporation. However, before the models can be integrated into the clinical workflow, e.g., for treatment planning, they need to be validated by experiments and (pre)clinical studies.
One of the most important applications of numerical modeling is computer-assisted treatment planning. A prerequisite for the success of all electroporation-based treatments is the complete coverage of the clinical target volume with a sufficiently high electric field. The distribution of the electric field in the tissue depends mainly on the electrode configuration and the parameters of the delivered pulse. Accurately determining the distribution of the electric field in the tissue, especially for deep-seated targets, is not a trivial task. Treatment planning based on patient-specific numerical models and optimization of treatment parameters, is advisable to ensure a successful treatment outcome. Despite the technological advances, treatment planning is still not part of the standard clinical practice for electroporation-based treatments; the major limitation stems from the fact that plans are currently generated prior to the procedure. The development of real-time treatment planning using actual electrode positions will allow real-time control of treatment parameters and outcome, and is a critical step toward introducing computer-assisted treatment planning into routine clinical practice.
The aim of this dissertation is to improve future electroporation-based treatments through numerical modeling and computer-assisted treatment planning. First, a brief introduction to the clinical application of electroporation is given; then, the fundamentals of treatment planning are described, followed by an overview of the numerical approaches used in modeling the electroporation phenomenon. The main body of the dissertation consists of six original research papers published in international journals that comprise the work performed in the dissertation. The methodology and results are discussed in detail in the papers, therefore only the discussion and conclusions of the presented papers are reproduced at the end of the dissertation.
Three original contributions to science are included within this dissertation. First, the numerical model of electroporation in the liver was validated using preclinical and clinical data. Second, the safety and efficacy aspects of electroporation-based treatments were numerically evaluated in risky clinical scenarios, such as near implanted pacemakers or in the presence of multiple metallic implants within the treatment zone. The feasibility and safety of a new treatment approach for spinal metastases was also numerically evaluated, demonstrating the utility of numerical modeling in the development of new treatments. Finally, an optimization algorithm for electrode placement was developed without using computationally intensive methods. The algorithm significantly reduces the time and expertise required to develop a treatment plan and is a step toward real-time treatment planning.
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