Measurement and simulation of Joule heating during treatment of B-16 melanoma tumors in mice with nanosecond pulsed electric fields
Measurement and simulation of Joule heating during treatment of B-16 melanoma tumors in mice with nanosecond pulsed electric fields
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DOI：
10.1016/j.bioelechem.2014.03.001
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发表时间：
2014-12-01
影响因子：
5
通讯作者：
Nuccitelli, Richard
中科院分区：
文献类型：
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作者：
Pliquett, Uwe;Nuccitelli, Richard
实验证据表明，纳秒脉冲电场（nsPEF）触发皮肤肿瘤细胞凋亡。我们假设nsPEF提供的能量不足以对治疗组织产生显着加热。为了验证这一假设，我们采用直接测量和理论建模的方法对焦耳加热进行了验证。对于温度测量，使用热敏液晶（TLC）来确定表面温度，而使用微型热电偶（由30 μ m的导线制成）来测量组织内部的温度。温度分布的计算使用渐进方法，重复计算电场、焦耳加热和热传递，以及随后重新调整组织电导率。这就产生了空间和时间上的温度分布。可以表明，对于所测量的温度升高，需要组织的出乎意料的高电导率，这确实是通过在实验期间使用电压和电流监测发现的。在t（后）= 50 μ s的脉冲后使用阻抗测量揭示了一个快速下降的高电导率状态时，电场停止。实验测量的板电极之间的皮肤褶皱（小鼠）的高电导率比由于完全电穿孔的膜结构（G（max）/G（电穿孔的））接近5而导致的最大预期电导率高约5倍。完全电穿孔的膜结构假定100%的膜是导电的，这是从10 MHz下的阻抗测量估计的，其中膜是电容性短路的。由于在B-16小鼠黑色素瘤肿瘤中由于E = 40 kV/cm的等间隔（Δ t = 2 s）的300 ns脉冲引起的温度升高在电极之间的皮肤褶皱的所有部分处通常不超过Δ T= 3 K，所以可以排除对组织的过热效应。(C)2014爱思唯尔有限公司版权所有。
Experimental evidence shows that nanosecond pulsed electric fields (nsPEF) trigger apoptosis in skin tumors. We have postulated that the energy delivered by nsPEF is insufficient to impart significant heating to the treated tissue. Here we use both direct measurements and theoretical modeling of the Joule heating in order to validate this assumption.For the temperature measurement, thermo-sensitive liquid crystals (TLC) were used to determine the surface temperature while a micro-thermocouple (made from 30 mu m wires) was used for measuring the temperature inside the tissue. The calculation of the temperature distribution used an asymptotic approach with the repeated calculation of the electric field, Joule heating and heat transfer, and the subsequent readjustment of the electrical tissue conductivity. This yields a temperature distribution both in space and time.It can be shown that for the measured increase in temperature an unexpectedly high electrical conductivity of the tissue would be required, which was indeed found by using voltage and current monitoring during the experiment. Using impedance measurements within t(after) = 50 mu s after the pulse revealed a fast decline of the high conductivity state when the electric field ceases. The experimentally measured high conductance of a skin fold (mouse) between plate electrodes was about 5 times higher than those of the maximally expected conductance due to fully electroporated membrane structures (G(max)/G(electroporated)) approximate to 5. Fully electroporated membrane structure assumes that 100% of the membranes are conductive which is estimated from an impedance measurement at 10 MHz where membranes are capacitively shorted. Since the temperature rise in B-16 mouse melanoma tumors due to equally spaced (Delta t = 2 s) 300 ns-pulses with E = 40 kV/cm usually does not exceed Delta T= 3 K at all parts of the skin fold between the electrodes, a hyperthermic effect on the tissue can be excluded. (C) 2014 Elsevier B.V. All rights reserved.