Search Results
Design, implementation, evaluation and application of a 32-channel radio frequency signal generator for thermal magnetic resonance based anti-cancer treatment
Thermal Magnetic Resonance (ThermalMR) leverages radio frequency (RF)-induced heating to examine the role of temperature in biological systems and disease. To advance RF heating with multi-channel RF antenna arrays and overcome the shortcomings of current RF signal sources, this work reports on a 32-channel modular signal generator (SGPLL). The SGPLL was designed around phase-locked loop (PLL) chips and a field-programmable gate array chip. To examine the system properties, switching/settling times, accuracy of RF power level and phase shifting were characterized. Electric field manipulation was successfully demonstrated in deionized water. RF heating was conducted in a phantom setup using self-grounded bow-tie RF antennae driven by the SGPLL. Commercial signal generators limited to a lower number of RF channels were used for comparison. RF heating was evaluated with numerical temperature simulations and experimentally validated with MR thermometry. Numerical temperature simulations and heating experiments controlled by the SGPLL revealed the same RF interference patterns. Upon RF heating similar temperature changes across the phantom were observed for the SGPLL and for the commercial devices. To conclude, this work presents the first 32-channel modular signal source for RF heating. The large number of coherent RF channels, wide frequency range and accurate phase shift provided by the SGPLL form a technological basis for ThermalMR controlled hyperthermia anti-cancer treatment. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Differences of the immune phenotype of breast cancer cells after ex vivo hyperthermia by warm-water or microwave radiation in a closed-loop system alone or in combination with radiotherapy
The treatment of breast cancer by radiotherapy can be complemented by hyperthermia. Little is known about how the immune phenotype of tumor cells is changed thereby, also in terms of a dependence on the heating method. We developed a sterile closed-loop system, using either a warm-water bath or a microwave at 2.45 GHz to examine the impact of ex vivo hyperthermia on cell death, the release of HSP70, and the expression of immune checkpoint molecules (ICMs) on MCF-7 and MDA-MB-231 breast cancer cells by multicolor flow cytometry and ELISA. Heating was performed between 39 and 44◦C. Numerical process simulations identified temperature distributions. Additionally, irradiation with 2 × 5 Gy or 5 × 2 Gy was applied. We observed a release of HSP70 after hyperthermia at all examined temperatures and independently of the heating method, but microwave heating was more effective in cell killing, and microwave heating with and without radiotherapy increased subsequent HSP70 concentrations. Adding hyperthermia to radiotherapy, dynamically or individually, affected the expression of the ICM PD-L1, PD-L2, HVEM, ICOS-L, CD137-L, OX40-L, CD27-L, and EGFR on breast cancer cells. Well-characterized pre-clinical heating systems are mandatory to screen the immune phenotype of tumor cells in clinically relevant settings to define immune matrices for therapy adaption. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.