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 (SG(PLL)). The SG(PLL) 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 SG(PLL). 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 SG(PLL) revealed the same RF interference patterns. Upon RF heating similar temperature changes across the phantom were observed for the SG(PLL) 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 SG(PLL) form a technological basis for ThermalMR controlled hyperthermia anti-cancer treatment

Radiofrequency antenna concepts for human cardiac MR at 14.0 T

OBJECTIVE: To examine the feasibility of human cardiac MR (CMR) at 14.0 T using high-density radiofrequency (RF) dipole transceiver arrays in conjunction with static and dynamic parallel transmission (pTx). MATERIALS AND METHODS: RF arrays comprised of self-grounded bow-tie (SGBT) antennas, bow-tie (BT) antennas, or fractionated dipole (FD) antennas were used in this simulation study. Static and dynamic pTx were applied to enhance transmission field (B(1)(+)) uniformity and efficiency in the heart of the human voxel model. B(1)(+) distribution and maximum specific absorption rate averaged over 10 g tissue (SAR(10g)) were examined at 7.0 T and 14.0 T. RESULTS: At 14.0 T static pTx revealed a minimum B(1)(+)(ROI) efficiency of 0.91 μT/√kW (SGBT), 0.73 μT/√kW (BT), and 0.56 μT/√kW (FD) and maximum SAR(10g) of 4.24 W/kg, 1.45 W/kg, and 2.04 W/kg. Dynamic pTx with 8 kT points indicate a balance between B(1)(+)(ROI) homogeneity (coefficient of variation  1.11 µT/√kW) at 14.0 T with a maximum SAR(10g) < 5.25 W/kg. DISCUSSION: MRI of the human heart at 14.0 T is feasible from an electrodynamic and theoretical standpoint, provided that multi-channel high-density antennas are arranged accordingly. These findings provide a technical foundation for further explorations into CMR at 14.0 T

Multi-channel RF supervision module for thermal magnetic resonance based cancer therapy

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

Radiofrequency applicator concepts for thermal magnetic resonance of brain tumors at 297 MHz (7.0 Tesla)

PURPOSE: Thermal intervention is a potent sensitizer of cells to chemo- and radiotherapy in cancer treatment. Glioblastoma multiforme (GBM) is a potential clinical target, given the cancer's aggressive nature and resistance to current treatment options. The annular phased array (APA) technique employing electromagnetic waves in the radiofrequency (RF) range allows for localized temperature increase in deep seated target volumes (TVs). Reports on clinical applications of the APA technique in the brain are still missing. Ultrahigh field magnetic resonance (MR) employs higher frequencies than conventional MR and has potential to provide focal temperature manipulation, high resolution imaging and noninvasive temperature monitoring using an integrated RF applicator (ThermalMR). This work examines the applicability of RF applicator concepts for ThermalMR of brain tumors at 297 MHz (7.0 Tesla). METHODS: Electromagnetic field (EMF) simulations are performed for clinically realistic data based on GBM patients. Two algorithms are used for specific RF energy absorption rate based thermal intervention planning for small and large TVs in the brain, aiming at maximum RF power deposition or RF power uniformity in the TV for 10 RF applicator designs. RESULTS: For both TVs , the power optimization outperformed the uniformity optimization. The best results for the small TV are obtained for the 16 element interleaved RF applicator using an elliptical antenna arrangement with water bolus. The two row elliptical RF applicator yielded the best result for the large TV. DISCUSSION: This work investigates the capacity of ThermalMR to achieve targeted thermal interventions in model systems resembling human brain tissue and brain tumors

Simultaneous T(2) and T(2)* mapping of multiple sclerosis lesions with radial RARE-EPI

PURPOSE: The characteristic MRI features of multiple sclerosis (MS) lesions make it conceptually appealing to pursue parametric mapping techniques that support simultaneous generation of quantitative maps of 2 or more MR contrast mechanisms. We present a modular rapid acquisition with relaxation enhancement (RARE)‐EPI hybrid that facilitates simultaneous T(2) and T(2)* mapping (2in1‐RARE‐EPI). METHODS: In 2in1‐RARE‐EPI the first echoes in the echo train are acquired with a RARE module, later echoes are acquired with an EPI module. To define the fraction of echoes covered by the RARE and EPI module, an error analysis of T(2) and T(2)* was conducted with Monte Carlo simulations. Radial k‐space (under)sampling was implemented for acceleration (R = 2). The feasibility of 2in1‐RARE‐EPI for simultaneous T(2) and T(2)* mapping was examined in a phantom study mimicking T(2) and T(2)* relaxation times of the brain. For validation, 2in1‐RARE‐EPI was benchmarked versus multi spin‐echo (MSE) and multi gradient‐echo (MGRE) techniques. The clinical applicability of 2in1‐RARE‐EPI was demonstrated in healthy subjects and MS patients. RESULTS: There was a good agreement between T(2)/T(2)* values derived from 2in1‐RARE‐EPI and T(2)/T(2)* reference values obtained from MSE and MGRE in both phantoms and healthy subjects. In patients, MS lesions in T(2) and T(2)* maps deduced from 2in1‐RARE‐EPI could be just as clearly delineated as in reference maps calculated from MSE/MGRE. CONCLUSION: This work demonstrates the feasibility of radially (under)sampled 2in1‐RARE‐EPI for simultaneous T(2) and T(2)* mapping in MS patients

Toward (19)F magnetic resonance thermometry: spin-lattice and spin-spin-relaxation times and temperature dependence of fluorinated drugs at 9.4 T

OBJECTIVE: This study examines the influence of the environmental factor temperature on the (19)F NMR characteristics of fluorinated compounds in phantom studies and in tissue. MATERIALS AND METHODS: (19)F MR mapping and MR spectroscopy techniques were used to characterize the (19)F NMR characteristics of perfluoro-crown ether (PFCE), isoflurane, teriflunomide, and flupentixol. T(1) and T(2) mapping were performed, while temperature in the samples was changed (T = 20-60 °C) and monitored using fiber optic measurements. In tissue, T(1) of PFCE nanoparticles was determined at physiological temperatures and compared with the T(1)-measured at room temperature. RESULTS: Studies on PFCE, isoflurane, teriflunomide, and flupentixol showed a relationship between temperature and their physicochemical characteristics, namely, chemical shift, T(1) and T(2). T(1) of PFCE nanoparticles was higher at physiological body temperatures compared to room temperature. DISCUSSION: The impact of temperature on the (19)F NMR parameters of fluorinated compounds demonstrated in this study not only opens a trajectory toward (19)F MR-based thermometry, but also indicates the need for adapting MR sequence parameters according to environmental changes such as temperature. This will be an absolute requirement for detecting fluorinated compounds by (19)F MR techniques in vivo

Radiofrequency antenna helmet array for thermal magnetic resonance of brain tumours at 297 MHz

Thermal magnetic resonance (Thermal MR) uses an RF-applicator to add a thermal intervention dimension to a diagnostic imaging device. Optimizing the performance of RF applicator configurations can eventually improve the performance of Themal MR. Recognizing this opportunity this work examines the feasibility of multi-channel RF applicators using broadband Self-Grounded Bow-Tie (SGBT) antenna building blocks. The focus is on enhancing focal RF power deposition in a target volume by using a multi-channel helmet RF array configuration versus conventional annular RF arrays. A 10-channel helmet RF applicator was designed for Thermal MR, evaluated in EMF simulations and benchmarked against an annular RF array using the same number of RF-elements. Our phantom studies demonstrate that the helmet RF applicator affords an ~10%- 30% improvement in maximum SAR10g in the TV over the conventional annular RF array. Our preliminary findings obtained for the human head voxel model Duke show improved target coverage of high SAR10g for the helmet RF applicator

Cardiorenal sodium MRI at 7.0 Tesla using a 4/4 channel (1)H/(23)Na radiofrequency antenna array

PURPOSE: Cardiorenal syndrome describes disorders of the heart and the kidneys in which a dysfunction of 1 organ induces a dysfunction in the other. This work describes the design, evaluation, and application of a 4/4-channel hydrogen-1/sodium ((1)H/(23)Na) RF array tailored for cardiorenal MRI at 7.0 Tesla (T) for a better physiometabolic understanding of cardiorenal syndrome. METHODS: The dual-frequency RF array is composed of a planar posterior section and a modestly curved anterior section, each section consisting of 2 loop elements tailored for (23)Na MR and 2 loopole-type elements customized for (1)H MR. Numerical electromagnetic field and specific absorption rate simulations were carried out. Transmission field (B(1)(+)) uniformity was optimized and benchmarked against electromagnetic field simulations. An in vivo feasibility study was performed. RESULTS: The proposed array exhibits sufficient RF characteristics, B(1)(+) homogeneity, and penetration depth to perform (23)Na MRI of the heart and kidney at 7.0 T. The mean B(1)(+) field for sodium in the heart is 7.7 ± 0.8 µT/√kW and in the kidney is 6.9 ± 2.3 µT/√kW. The suitability of the RF array for (23)Na MRI was demonstrated in healthy subjects (acquisition time for (23)Na MRI: 18 min; nominal isotropic spatial resolution: 5 mm [kidney] and 6 mm [heart]). CONCLUSION: This work provides encouragement for further explorations into densely packed multichannel transceiver arrays tailored for (23)Na MRI of the heart and kidney. Equipped with this technology, the ability to probe sodium concentration in the heart and kidney in vivo using (23)Na MRI stands to make a critical contribution to deciphering the complex interactions between both organs