Abstract

Simple SummaryGlioblastoma multiforme (GBM) is the most lethal brain tumor. Combining hyperthermia with chemotherapy and/or radiotherapy improves survival of GBM patients. For radio frequency (RF)-induced hyperthermia, the RF signals’ power and phase need to be supervised to achieve a precise formation of the power deposition focal point, accurate thermal dose control, and safety management. Patient position during treatment also needs to be monitored to ensure the efficiency of the treatment and to avoid adverse effects in healthy tissue. This work demonstrates the development, implementation, evaluation, validation, and application of a multi-channel RF supervision module that meets the technical requirements of hyperthermia and provides a cost-effective solution for broad-band RF signal supervision and patient monitoring. It is a key component for a hyperthermia hardware system and facilitates future thermal magnetic resonance applications that integrate RF-induced heating, in vivo temperature mapping, and anatomic and functional imaging in a single RF applicator.Glioblastoma multiforme (GBM) is the most lethal and common brain tumor. Combining hyperthermia with chemotherapy and/or radiotherapy improves the survival of GBM patients. Thermal magnetic resonance (ThermalMR) is a hyperthermia variant that exploits radio frequency (RF)-induced heating to examine the role of temperature in biological systems and disease. The RF signals’ power and phase need to be supervised to manage the formation of the energy focal point, accurate thermal dose control, and safety. Patient position during treatment also needs to be monitored to ensure the efficacy of the treatment and avoid damages to healthy tissue. This work reports on a multi-channel RF signal supervision module that is capable of monitoring and regulating RF signals and detecting patient motion. System characterization was performed for a broad range of frequencies. Monte-Carlo simulations were performed to examine the impact of power and phase errors on hyperthermia performance. The supervision module’s utility was demonstrated in characterizing RF power amplifiers and being a key part of a feedback control loop regulating RF signals in heating experiments. Electromagnetic field simulations were conducted to calculate the impact of patient displacement during treatment. The supervision module was experimentally tested for detecting patient motion to a submillimeter level. To conclude, this work presents a cost-effective RF supervision module that is a key component for a hyperthermia hardware system and forms a technological basis for future ThermalMR applications.

Highlights

  • Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, accounting for 14.6% of all primary brain tumors and 57.3% of all gliomas [1]

  • Equation (1) describes curve fitting results of the meter (ADCref represents the reading from the analog-to-digital converter (ADC) and Freq is the signal frequency in MHz)

  • The HYPERcollar [47] system, which utilizes the same power detector chip used in our work, operates at 433.92 MHz

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Summary

Introduction

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, accounting for 14.6% of all primary brain tumors and 57.3% of all gliomas [1]. Less than 5.8% of patients survive five years post diagnosis, which renders GBM the most lethal type of brain tumor [1]. Surgical resection followed by radiotherapy and chemotherapy remains the mainstay of care for GBM patients [2,3]. Adding thermal therapy to the standard treatment of GBM could improve prognosis [4]. Mild regional hyperthermia (HT; 40–44 ◦C for 60–90 min) is a clinically proven adjuvant anti-cancer treatment in conjunction with radiotherapy and/or chemotherapy that significantly improves survival [5,6,7,8,9]. Non-invasive HT modalities targeting the GBM mainly include magnetic nanoparticle hyperthermia (MNH), focused ultrasound-based hyperthermia, and radio frequency (RF)-induced hyperthermia. 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

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