Mitigation of eddy current heating during magnetic nanoparticle hyperthermia therapy

Abstract

Magnetic nanoparticle hyperthermia therapy is a promising technology for cancer treatment. The technique involves delivering magnetic nanoparticles (MNPs) into tumors, then activating the MNPs using an alternating magnetic field (AMF). The AMF generating system produces not only a magnetic field, but also an electric field. The electric field penetrates normal tissue and induces eddy currents, which result in unwanted heating of normal tissues. The magnitude of the eddy current depends, in part, on the AMF source and the size of the tissue exposed to the field. The majority of in vivo MNP hyperthermia therapy studies have been performed in small animals, which, due to the spatial distribution of the AMF relative to the size of the animals, do not reveal the potential toxicity of eddy current heating in larger tissues. This limitation has posed a nontrivial challenge for researchers who have attempted to scale up from a small animal model to clinically relevant volumes of tissue. For example, the efficacy limiting nature of eddy current heating has been observed in a recent clinical trial, where patient discomfort was reported. Until now, much of the literature regarding increasing the efficacy of MNP hyperthermia therapy has focused on increasing MNP specific absorption rate or increasing the concentration of MNPs in the tumor; i.e. - improving efficacy at what is thought to be the maximum safe field strength and frequency. There has been a relative dearth of studies focused on decreasing the maximum temperature resulting from eddy current heating, to increase therapeutic ratio. This paper presents two simple and clinically applicable techniques for decreasing maximum temperature induced by eddy currents. Computational and experimental results are presented to understand the underlying physics of eddy currents induced in conducting, biological tissues and to leverage these insights for the mitigation of eddy current heating during MNP hyperthermia therapy. Phantom studies show that these techniques, termed the displacement and motion techniques, reduce maximum temperature due to eddy currents by 74% and 19% in simulation, and by 77% and 33% experimentally. Further study is required to optimize these methods for particular scenarios; however, these results suggest larger volumes of tissue could be treated, and/or higher field strengths and frequencies could be used to attain increased MNP heating, when these eddy current mitigation techniques are employed.

Biocompatible Nanoclusters with High Heating Efficiency for Systemically Delivered Magnetic Hyperthermia

“…1,10,58 Notably, the maximum allowed frequency and strength of AMF that can be considered safe and tolerable is not completely agreed upon by the magnetic hyperthermia community, and the main requirement is to minimize non-specific heating to tissue due to eddy currents generated by AMF alone. 31,59 Currently, several groups work on the development of different strategies to decrease eddy current heating during magnetic hyperthermia 57 and, therefore the suggested upper limit for the product of frequency and field strength may be reconsidered in the future. Consequently, clinical safety studies will be needed for each developed magnetic hyperthermia regimen achieved with the specific AMF system.…”

Design and construction of a Maxwell-type induction coil for magnetic nanoparticle hyperthermia

“…fields having amplitude that rapidly decays with distance normal to the coil plane. Such coils are able to provide sufficient field amplitude to generate effective heating for nearsurface tumors ($2 cm) [12,19,54].…”

Therapeutic Efficiency of Multiple Applications of Magnetic Hyperthermia Technique in Glioblastoma Using Aminosilane Coated Iron Oxide Nanoparticles: In Vitro and In Vivo Study

“…The highest SAR value was obtained by the combination of 557 kHz oscillation frequency with 300 Gauss magnetic field and it was the parameter chosen for the in vitro studies. Considering the fact that high frequencies can cause undesirable electric currents [66], another parameter with high SAR but low-frequency values, such as a combination between 309 kHz and 300 Gauss, was also chosen. Thus, two combinations of AMF were included for in vitro MHT evaluation in multiple applications: 557 kHz, 300 Gauss, and 309 kHz, 300 Gauss.…”