Design, Implementation, Evaluation and Application of a 32-Channel Radio Frequency Signal Generator for Thermal Magnetic Resonance Based Anti-Cancer Treatment

Abstract

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.

Multi-Channel RF Supervision Module for Thermal Magnetic Resonance Based Cancer Therapy

“…The schematic of the experimental setup is illustrated in Figure 3 B. Two coherent RF signals generated from the custom-built RF signal generator [ 15 ] were fed to the same two RFPAs that were characterized with the supervision module. The amplified signals were connected to two wideband self-grounded bow-tie (SGBT) antennas [ 14 ] through two directional couplers (BDC0810-50/1500, BONN Elektronik, Holzkirchen, Germany) and the feed-through penetration panel of the MR scanner room.…”

“…The amplified signals were connected to two wideband self-grounded bow-tie (SGBT) antennas [ 14 ] through two directional couplers (BDC0810-50/1500, BONN Elektronik, Holzkirchen, Germany) and the feed-through penetration panel of the MR scanner room. The antennas were positioned opposite to each other and applied to a muscle-mimicking agarose phantom (length = 160 mm, width = 116 mm, height = 178 mm; ε r = 54.32, and σ = 0.25 S/m [ 15 ]). The phantom was placed in the isocenter of a 7.0 T human MR scanner (Magnetom, Siemens Healthineers, Erlangen, Germany).…”

“…MR thermometry utilizing the proton-resonance-frequency-shift (PRFS) approach [ 36 , 37 ] (TR = 99 ms, TE1 = 2.73 ms, TE2 = 6.71 ms, and voxel size = 1.0 × 1.0 × 5.0 mm 3 [ 15 ]) at 297.2 MHz was conducted before and after each experiment. Vegetable oil was used as a reference to correct the magnetic field drifts [ 15 , 38 ]. Fiber optic temperature sensors (Neoptix, Quebec, QC, Canada) were used to validate the MRT results [ 15 ].…”

“…Vegetable oil was used as a reference to correct the magnetic field drifts [ 15 , 38 ]. Fiber optic temperature sensors (Neoptix, Quebec, QC, Canada) were used to validate the MRT results [ 15 ]. For benchmarking experimental data with numerical simulations, temperature simulations using the same frequency, power, and phase settings (400 MHz, 42.5 dBm, and ϕ = 0° for both channels at the feeding port of the SGBT antenna) were performed in CST Microwave Studio 2018 (Computer Simulation Technology GmbH, Darmstadt, Germany).…”

“…A significant improvement of survival was reported for GBM patients receiving chemotherapy together with RF-induced HT [ 10 ]. Thermal magnetic resonance (ThermalMR) is an HT variant that integrates RF-induced heating [ 11 , 12 , 13 , 14 , 15 ], in vivo temperature mapping using MR thermometry (MRT) [ 16 , 17 , 18 , 19 ], anatomic and functional MR imaging (MRI), and the option for x-nuclei MRI in a single, multi-purpose RF applicator that permits supervised targeted temperature modulation.…”