In silico evaluation of adverse eddy current effects in preclinical tests of magnetic hyperthermia. (August 2022)

• Record Type: Journal Article
• Authors: Vicentini, Marta; Vassallo, Marta; Ferrero, Riccardo; Androulakis, Ioannis; Manzin, Alessandra
• Is Part Of: Computer methods and programs in biomedicine. Volume 223(2022)
• Publication Date: 2022-08
• Subjects: Bio-heat transfer model -- Magnetic hyperthermia -- Magnetic nanoparticles -- Magnetic field applicators -- Numerical simulations -- Specific absorption rate -- In silico modelling -- Computational animal models -- Preclinical tests; Medicine -- Computer programs -- Periodicals; Biology -- Computer programs -- Periodicals; Computers -- Periodicals; Medicine -- Periodicals; Médecine -- Logiciels -- Périodiques; Biologie -- Logiciels -- Périodiques; Biology -- Computer programs; Medicine -- Computer programs; Periodicals; Electronic journals; 610.28
• DOI: 10.1016/j.cmpb.2022.106975
• Languages: English
• ISSNs: 0169-2607

Abstract

Highlights: Development and validation of in silico models, as a tool to investigate adverse eddy current effects during magnetic hyperthermia tests on mice and rats and to define safe EM field exposure levels. Weak eddy current effects observed in mice for a large range of AC magnetic field parameters: maximum temperature increase of 0.25 °C and 0.8 °C in proximity to Hergt-Dutz limit and 4 W/kg SAR threshold, respectively. Important eddy current effects observed in rats: maximum temperature increase around 7 °C found at the Hergt-Dutz limit, for magnetic fields applied along the body longitudinal axis. Stronger eddy current effects when the magnetic field is applied transversally: maximum temperature increase around 14 °C found in rats at the Hergt-Dutz limit. Mitigation of eddy current heating with the introduction of water boluses and the use of applicators targeted to tumour region size and position in the body. Abstract: Background and Objective: 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. Methods: 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. Results: 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 9 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. Conclusions: 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.