Validation of a Temperature-Feedback Controlled Automated Magnetic Hyperthermia Therapy Device

SIMPLE SUMMARY: Magnetic hyperthermia therapy (MHT) is a promising nanotechnology-based treatment for cancer. Its widespread adoption is hampered by the imprecise control of tumor temperature during treatment and by a lack of automatic shutdown to avoid adverse events. Here, we verify the functionality and validate performance of an automated temperature controller, and the functionality of automated safety shutdowns. Experiments were performed ex vivo in liver tissue and in vivo in the brain of a healthy live research subject to demonstrate the potential for superior energy control with temperature stability using user-defined inputs, and real-time temperature monitoring for feedback. Performance of this device was validated against design criteria using FDA guidelines. It will be used to treat canine glioblastoma tumors in a future study. ABSTRACT: We present in vivo validation of an automated magnetic hyperthermia therapy (MHT) device that uses real-time temperature input measured at the target to control tissue heating. MHT is a thermal therapy that uses heat generated by magnetic materials exposed to an alternating magnetic field. For temperature monitoring, we integrated a commercial fiber optic temperature probe containing four gallium arsenide (GaAs) temperature sensors. The controller device used temperature from the sensors as input to manage power to the magnetic field applicator. We developed a robust, multi-objective, proportional-integral-derivative (PID) algorithm to control the target thermal dose by modulating power delivered to the magnetic field applicator. The magnetic field applicator was a 20 cm diameter Maxwell-type induction coil powered by a 120 kW induction heating power supply operating at 160 kHz. Finite element (FE) simulations were performed to determine values of the PID gain factors prior to verification and validation trials. Ex vivo verification and validation were conducted in gel phantoms and sectioned bovine liver, respectively. In vivo validation of the controller was achieved in a canine research subject following infusion of magnetic nanoparticles (MNPs) into the brain. In all cases, performance matched controller design criteria, while also achieving a thermal dose measured as cumulative equivalent minutes at 43 °C (CEM43) 60 ± 5 min within 30 min.