Iredale Erin, Elsaleh Abdulla, Xu Hu, Christiaans Paul, Deweyert Andrew, Ronald John, Schmid Susanne, Hebb Matthew O, Peters Terry M, Wong Eugene
Department of Medical Biophysics, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
Phys Med Biol. 2023 Apr 5;68(8). doi: 10.1088/1361-6560/acc308.
. The treatment of glioblastoma (GBM) using low intensity electric fields (∼1 V cm) is being investigated using multiple implanted bioelectrodes, which was termed intratumoral modulation therapy (IMT). Previous IMT studies theoretically optimized treatment parameters to maximize coverage with rotating fields, which required experimental investigation. In this study, we employed computer simulations to generate spatiotemporally dynamic electric fields, designed and purpose-built an IMT device forexperiments, and evaluated the human GBM cellular responses to these fields.. After measuring the electrical conductivity of theculturing medium, we designed experiments to evaluate the efficacy of various spatiotemporally dynamic fields: (a) different rotating field magnitudes, (b) rotating versus non-rotating fields, (c) 200 kHz versus 10 kHz stimulation, and (d) constructive versus destructive interference. A custom printed circuit board (PCB) was fabricated to enable four-electrode IMT in a 24-well plate. Patient derived GBM cells were treated and analyzed for viability using bioluminescence imaging.. The optimal PCB design had electrodes placed 6.3 mm from the center. Spatiotemporally dynamic IMT fields at magnitudes of 1, 1.5, and 2 V cmreduced GBM cell viability to 58%, 37% and 2% of sham controls respectively. Rotating versus non-rotating, and 200 kHz versus 10 kHz fields showed no statistical difference. The rotating configuration yielded a significant reduction (< 0.01) in cell viability (47 ± 4%) compared to the voltage matched (99 ± 2%) and power matched (66 ± 3%) destructive interference cases.. We found the most important factors in GBM cell susceptibility to IMT are electric field strength and homogeneity. Spatiotemporally dynamic electric fields have been evaluated in this study, where improvements to electric field coverage with lower power consumption and minimal field cancellations has been demonstrated. The impact of this optimized paradigm on cell susceptibility justifies its future use in preclinical and clinical trial investigations.
目前正在研究使用多个植入式生物电极，利用低强度电场（约1 V/cm）治疗胶质母细胞瘤（GBM），这一疗法被称为瘤内调制疗法（IMT）。此前的IMT研究在理论上优化了治疗参数，以通过旋转场实现最大覆盖范围，这需要进行实验研究。在本研究中，我们采用计算机模拟来生成时空动态电场，设计并专门制造了用于实验的IMT设备，并评估了人GBM细胞对这些电场的反应。在测量了培养基的电导率后，我们设计实验来评估各种时空动态电场的疗效：（a）不同的旋转场强度，（b）旋转场与非旋转场，（c）200 kHz与10 kHz刺激，以及（d）相长干涉与相消干涉。制作了定制印刷电路板（PCB），以在24孔板中实现四电极IMT。使用生物发光成像对患者来源的GBM细胞进行处理并分析其活力。最佳的PCB设计是电极距离中心6.3 mm。强度为1、1.5和2 V/cm的时空动态IMT场分别将GBM细胞活力降低至假对照的58%、37%和2%。旋转场与非旋转场以及200 kHz与10 kHz场之间没有统计学差异。与电压匹配（99±2%）和功率匹配（66±3%）的相消干涉情况相比，旋转配置使细胞活力显著降低（<0.01）（47±4%）。我们发现GBM细胞对IMT敏感性的最重要因素是电场强度和均匀性。本研究对时空动态电场进行了评估，结果表明通过更低的功耗和最小的场抵消实现了电场覆盖范围的改善。这种优化模式对细胞敏感性的影响证明了其在临床前和临床试验研究中的未来应用价值。
