Istituto Nazionale di Ricerca Metrologica (INRIM), Strada delle Cacce 91, 10135 Torino, Italy; Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy.
Istituto Nazionale di Ricerca Metrologica (INRIM), Strada delle Cacce 91, 10135 Torino, Italy.
Comput Methods Programs Biomed. 2022 Aug;223:106975. doi: 10.1016/j.cmpb.2022.106975. Epub 2022 Jun 25.
Magnetic hyperthermia is an oncological therapy that employs magnetic nanoparticles activated by alternating current (AC) magnetic fields with frequencies between 50 kHz and 1 MHz, to release heat in a diseased tissue and produce a local temperature increase of about 5 °C. To assess the treatment efficacy, in vivo tests on murine models (mice and rats) are typically performed. However, these are often carried out without satisfying the biophysical constraints on the electromagnetic (EM) field exposure, with consequent generation of hot spots and undesirable heating of healthy tissues. Here, we investigate possible adverse eddy current effects, to estimate AC magnetic field parameters (frequency and amplitude) that can potentially guarantee safe animal tests of magnetic hyperthermia.
The analysis is performed through in silico modelling by means of finite element simulation tools, specifically developed to study eddy current effects in computational animal models, during magnetic hyperthermia treatments. The numerical tools enable us to locally evaluate the specific absorption rate (SAR) and the produced temperature increase, under different field exposure conditions.
The simulation outcomes demonstrate that in mice with weight lower than 30 g the thermal effects induced by AC magnetic fields are very weak, also when slightly overcoming the Hergt-Dutz limit, that is the product of the magnetic field amplitude and frequency should be lower than 5·10 A/(m·s). Conversely, we observe significant temperature increases in 500 g rats, amplified when the field is applied transversally to the body longitudinal axis. A strong mitigation of side-effects can be achieved by introducing water boluses or by applying focused fields.
The developed physics-based modelling approach has proved to be a useful predictive tool for the optimization of preclinical tests of magnetic hyperthermia, allowing the identification of proper EM field conditions and the design of setups that guarantee safe levels of field exposure during animal treatments. In such contest, the obtained results can be considered as valid indicators to assess reference levels for animal testing of biomedical techniques that involve EM fields, like magnetic hyperthermia, thus complying with the Directive 2010/63/EU on the protection of animals used for scientific purposes.
磁热疗是一种利用交流（AC）磁场中频率在 50 kHz 至 1 MHz 之间的磁性纳米粒子释放病变组织热量并产生约 5°C 局部温度升高的肿瘤治疗方法。为了评估治疗效果，通常在小鼠模型（小鼠和大鼠）上进行体内测试。然而，这些测试通常不满足电磁（EM）场暴露的生物物理限制，从而产生热点和对健康组织的不良加热。在这里，我们研究了可能存在的涡流效应，以估计可能保证磁性热疗安全动物试验的 AC 磁场参数（频率和幅度）。
通过有限元模拟的计算建模来进行分析，具体使用专门开发的计算动物模型中的涡流效应研究工具，在磁热疗治疗期间进行。这些数值工具使我们能够在不同的场暴露条件下局部评估比吸收率（SAR）和产生的温升。
模拟结果表明，体重低于 30 g 的小鼠中，由 AC 磁场引起的热效应非常微弱，即使略微超过赫格特-杜茨极限，即磁场幅度和频率的乘积应低于 5·10 A/（m·s）也是如此。相反，我们观察到 500 g 大鼠的体温显著升高，当磁场沿身体纵轴横向施加时会加剧这种升高。通过引入水囊或应用聚焦场，可以实现对副作用的强烈缓解。
所开发的基于物理的建模方法已被证明是优化磁热疗临床前测试的有用预测工具，允许确定适当的 EM 场条件并设计保证动物治疗期间安全场暴露水平的设置。在这种情况下，获得的结果可以被视为评估涉及 EM 场的生物医学技术（如磁热疗）动物测试参考水平的有效指标，从而符合 2010/63/EU 号指令关于用于科学目的的动物保护。
