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Numerical modeling in electroporation-based biomedical applications

机译:基于电穿孔的生物医学应用中的数值建模

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Background. Numerous experiments have to be performed before a biomedical application is put to practical use in clinical environment. As a complementary work to in vitro, in vivo and medical experiments, we can use analytical and numerical models to represent, as realistically as possible, real biological phenomena of, in our case, electroporation. In this way we can evaluate different electrical parameters in advance, such as pulse amplitude, duration, number of pulses, or different electrode geometries. Such numerical models can contribute significantly to the understanding of an experiment and treatment planning as well as to the design of new electroporation devices and electrodes.Methods. We used commercially available modeling software, based on finite element method. We constructed a model of a subcutaneous tumor during electrochemotherapy (EMAS) and a model of skin during gene electrotransfer (COMSOL Multiphysics). Tissue-electrode geometries, pulse parameters and currentvoltage measurements from in vivo experiments were used to develop and validate the models.Results. To describe adequately our in vivo observations, a tissue conductivity increase during electroporation was included in our numerical models. The output currents of the models were compared to the currents and the voltages measured during in vivo experiments and a good agreement was obtained. Also, when comparing the voltages needed for a successful electropermeabilization as suggested by the models, to voltages applied in experiments and achieving a successful electrochemotherapy or in vivo gene electrotransfer, good agreement can be observed.Conclusions. Modeling of electric current and electric field distribution during cell and tissue electroporation proves to be helpful in describing different aspects of the process and allowing us to design electrodes and electroporation protocols as a part of treatment planning.
机译:背景。在生物医学应用在临床环境中投入实际使用之前,必须进行大量实验。作为体外,体内和医学实验的补充工作,我们可以使用分析模型和数值模型来尽可能现实地表示电穿孔的真实生物学现象。通过这种方式,我们可以预先评估不同的电参数,例如脉冲幅度,持续时间,脉冲数或不同的电极几何形状。这样的数值模型可以极大地有助于对实验和治疗计划的理解以及新的电穿孔设备和电极的设计。我们使用了基于有限元方法的市售建模软件。我们构建了电化学疗法(EMAS)期间的皮下肿瘤模型和基因电转移(COMSOL Multiphysics)期间的皮肤模型。通过体内实验的组织电极几何形状,脉冲参数和电流电压测量值来开发和验证模型。为了充分描述我们的体内观察,我们的数字模型包括电穿孔过程中组织电导率的增加。将模型的输出电流与在体内实验期间测量的电流和电压进行比较,并获得了良好的一致性。此外,当将模型建议的成功电透化所需的电压与实验中施加的电压以及实现成功的电化学疗法或体内基因电转移的电压进行比较时,可以观察到良好的一致性。在细胞和组织电穿孔过程中对电流和电场分布进行建模被证明有助于描述过程的不同方面,并允许我们设计电极和电穿孔方案作为治疗计划的一部分。

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