Mitigation of magnetic particle hyperthermia side effects by magnetic field controls

Abstract

Objective: In magnetic particle hyperthermia, a promising least-invasive cancer treatment, malignant regions in proximity with magnetic nanoparticles undergo heat stress, while unavoidably surrounding healthy tissues may also suffer from heat either directly or indirectly by the induced eddy currents, due to the developed electric fields as well. Here, we propose a facile upgrade of a typical magnetic particle hyperthermia protocol, to selectively mitigate eddy currents' heating without compromising the beneficial role of heating in malignant regions. Method:The key idea is to apply the external magnetic field intermittently (in an ON/OFF pulse mode), instead of the continuous field mode typically applied. The parameters of the intermittent field mode, such as time intervals (ON time: 25-100 s, OFF time: 50-200 s, Duty Cycle:16-100%) and field amplitude (30-70 mT) are optimized based on evaluation on healthy tissue and cancer tissue phantoms. The goal is to sustain in cancer tissue phantom the maximum temperature increase (preferably within 4-8 C above body temperature of 37 C), while in the healthy tissue phantom temperature variation is suppressed far below the 4 C dictating the eddy current mitigation. Results: Optimum conditions of intermittent field (ON/OFF: 50/100 in s, Duty Cycle: 33%, magnetic field: 45mT) are then examined in ex-vivo samples verifying the successful suppression of eddy currents. Simultaneously, a well-elaborated theoretical approach provides a rapid calculation of temperature increase and, furthermore, the ability to quickly simulate a variety of duty cycle times and field controls may save experimental time. Conclusion: Eventually, the application of an intermittent field mode in a magnetic particle hyperthermia protocol, succeeds in eddy current mitigation in surrounding tissues and allows for the application of larger field amplitudes that may augment hyperthermia efficiency without objecting typical biomedical applicability field constraints such as Brezovich criterion.

Numerical Simulation of Temperature Variations during the Application of Safety Protocols in Magnetic Particle Hyperthermia

“…In order to test the reliability of the proposed strategy, the numerical results were compared to the corresponding experimental ones, as obtained in [ 23 ] after temperature measurements, by applying either a continuous AMF or a PMF of 45 mT, as shown in Figure 11 .…”

“…One way to express the ratio between ON and OFF times is the Duty Cycle, shown in Equation (1). The role of pulsed AMF—that is, Duty Cycles—to reducing eddy current heating was based on our previously reported study [ 23 ]. This quantity is defined as the percentage of the time the coil is in operation (ON) to the total time of a cycle (ON + OFF).…”

“…The device used to conduct the MPH experiments consisted of a common coil (1.2 kW Ambrell Easyheat 0112, New York, United States), which induces an alternating magnetic field of frequency 375 kHz and amplitude 30–70 mT, according to the applied AC current. The magnetic field calibration for the various AC amplitudes had been achieved in our previous work by employing electromagnetic simulations with a suitable finite elements method (FEM) model of the used experimental setup [ 23 ], as shown in Figures S1 and S2 of the Supplementary Materials . As shown in Figure 2 , an optical fiber was positioned in the center of the phantom, which is placed in a beaker, and the temperature was measured at this point with a time step of 0.4 s. The measurements were recorded with appropriate software.…”

“…Pulsed AMF—that is, reduced Duty Cycle—dissipates heat generated by eddy currents as demonstrated in literature. In Tsiapla et al [ 23 ] the role of an intermittently applied AMF was evaluated on the thermal response of iron oxide (Fe 3 O 4 ) MNPs dispersed in phantom and ex vivo samples with respect to field parameters and in direct comparison with the corresponding continuously applied AMF. The parameters of the intermittent field mode, such as time intervals (ON time: 25–100 s, OFF time: 50–200 s, Duty Cycle: 16–100%) and field amplitude (30–70 mT) were optimized based on computations with healthy tissue and cancer tissue phantoms.…”

Theoretical Analysis for Using Pulsed Heating Power in Magnetic Hyperthermia Therapy of Breast Cancer

“…Temperature was regulated by varying the pulse for a specific amplitude and duty combination and finally the choice of the duty and cycle at amplitudes greater than 700 Oe was considered to prevent damage to the healthy tissues. Similarly, the optimum condition of intermittent field was also considered in [32]. The duty cycle of 33% with the ON/OFF condition of 50/100 in second for the intermittent magnetic field mode was shown to mitigate the eddy current in normal tissues.…”