Objective: To evaluate the effect of a closed-loop temperature based feedback algorithm on ablative outcomes for pulsed electric field treatments. Methods: A 3D tumor model of glioblastoma was used to assess the impact of 2 μs duration bipolar waveforms on viability following exposure to open and closed-loop protocols. Closed-loop treatments evaluated transient temperature increases of 5, 10, 15, or 22 °C above baseline. Results: The temperature controlled ablation diameters were conditionally different than the open-loop treatments and closed-loop treatments generally produced smaller ablations. Closed-loop control enabled the investigation of treatments with steady state 42 °C hyperthermic conditions which were not feasible without active feedback. Baseline closed-loop treatments at 20 °C resulted in ablations measuring 9.9 ± 0.3 mm in diameter while 37 °C treatments were 20% larger (p < 0.0001) measuring 11.8 ± 0.3 mm indicating that this protocol induces a thermally mediated biological response. Conclusion: A closed-loop control algorithm which modulated the delay between successive pulse waveforms to achieve stable target temperatures was demonstrated. Algorithmic control enabled the evaluation of specific treatment parameters at physiological temperatures not possible with open-loop systems due to excessive Joule heating. Significance: Irreversible electroporation is generally considered to be a non-thermal ablation modality and temperature monitoring is not part of the standard clinical practice. The results of this study indicate ablative outcomes due to exposure to pulses on the order of one microsecond may be thermally mediated and dependent on local tissue temperatures. The results of this study set the foundation for experiments in vivo utilizing temperature control algorithms.

中文翻译：

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算法控制的电穿孔：一种闭环温度调节脉冲电场癌症消融技术

目的：评估基于闭环温度的反馈算法对脉冲电场治疗的消融结果的影响。方法：胶质母细胞瘤的 3D 肿瘤模型用于评估持续时间为 2 μs 的双极波形对暴露于开环和闭环协议后生存能力的影响。闭环治疗评估了高于基线 5、10、15 或 22°C 的瞬时温度升高。结果：温度控制的消融直径在条件上与开环治疗不同，闭环治疗通常产生较小的消融。闭环控制使研究具有稳态 42 °C 高温条件的治疗成为可能，如果没有主动反馈，这是不可行的。20 °C 的基线闭环治疗导致消融测量值为 9.9 ± 0。直径为 3 毫米，而 37 °C 处理大 20%（p < 0.0001），测量值为 11.8 ± 0.3 毫米，表明该协议诱导了热介导的生物反应。结论： 展示了一种闭环控制算法，该算法调制连续脉冲波形之间的延迟以实现稳定的目标温度。算法控制使得在生理温度下评估特定治疗参数成为可能，由于过度焦耳加热，开环系统无法实现。意义：不可逆电穿孔通常被认为是一种非热消融方式，温度监测不是标准临床实践的一部分。这项研究的结果表明，由于暴露于一微秒量级的脉冲而导致的烧蚀结果可能是热介导的，并且取决于局部组织温度。这项研究的结果为利用温度控制算法的体内实验奠定了基础。