Advanced Radio Frequency Applicators for Thermal Magnetic Resonance Theranostics of Brain Tumors.

Thermal Magnetic Resonance (ThermalMR) is a theranostic concept that combines diagnostic magnetic resonance imaging (MRI) with targeted thermal therapy in the hyperthermia (HT) range using a radiofrequency (RF) applicator in an integrated system. ThermalMR adds a therapeutic dimension to a diagnostic MRI device. Focused, targeted RF heating of deep-seated brain tumors, accurate non-invasive temperature monitoring and high-resolution MRI are specific requirements of ThermalMR that can be addressed with novel concepts in RF applicator design. This work examines hybrid RF applicator arrays combining loop and self-grounded bow-tie (SGBT) dipole antennas for ThermalMR of brain tumors, at magnetic field strengths of 7.0 T, 9.4 T and 10.5 T. These high-density RF arrays improve the feasible transmission channel count, and provide additional degrees of freedom for RF shimming not afforded by using dipole antennas only, for superior thermal therapy and MRI diagnostics. These improvements are especially relevant for ThermalMR theranostics of deep-seated brain tumors because of the small surface area of the head. ThermalMR RF applicators with the hybrid loop+SGBT dipole design outperformed applicators using dipole-only and loop-only designs, with superior MRI performance and targeted RF heating. Array variants with a horse-shoe configuration covering an arc (270°) around the head avoiding the eyes performed better than designs with 360° coverage, with a 1.3 °C higher temperature rise inside the tumor while sparing healthy tissue. Our EMF and temperature simulations performed on a virtual patient with a clinically realistic intracranial tumor provide a technical foundation for implementation of advanced RF applicators tailored for ThermalMR theranostics of brain tumors.

Radiofrequency induced heating of biodegradable orthopaedic screw implants during magnetic resonance imaging.

Magnesium (Mg)-based implants have re-emerged in orthopaedic surgery as an alternative to permanent implants. Literature reveals little information on how the degradation of biodegradable implants may introduce safety implications for patient follow-up using medical imaging. Magnetic resonance imaging (MRI) benefits post-surgery monitoring of bone healing and implantation sites. Previous studies demonstrated radiofrequency (RF) heating of permanent implants caused by electromagnetic fields used in MRI. Our investigation is the first to report the effect of the degradation layer on RF-induced heating of biodegradable orthopaedic implants. WE43 orthopaedic compression screws underwent in vitro degradation. Imaging techniques were applied to assess the corrosion process and the material composition of the degraded screws. Temperature measurements were performed to quantify implant heating with respect to the degradation layer. For comparison, a commercial titanium implant screw was used. Strongest RF induced heating was observed for non-degraded WE43 screw samples. Implant heating had shown to decrease with the formation of the degradation layer. No statistical differences were observed for heating of the non-degraded WE43 material and the titanium equivalent. The highest risk of implant RF heating is most pronounced for Mg-based screws prior to degradation. Amendment to industry standards for MRI safety assessment is warranted to include biodegradable materials.

Evaluating metallic artefact of biodegradable magnesium-based implants in magnetic resonance imaging.

Magnesium (Mg) implants have shown to cause image artefacts or distortions in magnetic resonance imaging (MRI). Yet, there is a lack of information on how the degradation of Mg-based implants influences the image quality of MRI examinations. In this study, Mg-based implants are analysed in vitro, ex vivo, and in the clinical setting for various magnetic field strengths with the aim to quantify metallic artefact behaviour. In vitro corroded Mg-based screws and a titanium (Ti) equivalent were imaged according to the ASTM F2119. Mg-based and Ti pins were also implanted into rat femurs for different time points and scanned to provide insights on the influence of soft and hard tissue on metallic artefact. Additionally, MRI data of patients with scaphoid fractures treated with CE-approved Mg-based compression screws (MAGNEZIX®) were analysed at various time points post-surgery. The artefact production of the Mg-based material decreased as implant material degraded in all settings. The worst-case imaging scenario was determined to be when the imaging plane was selected to be perpendicular to the implant axis. Moreover, the Mg-based implant outperformed the Ti equivalent in all experiments by producing lower metallic artefact (p < 0.05). This investigation demonstrates that Mg-based implants generate significantly lower metallic distortion in MRI when compared to Ti. Our positive findings suggest and support further research into the application of Mg-based implants including post-operative care facilitated by MRI monitoring of degradation kinetics and bone/tissue healing processes.

Patient-Specific Planning for Thermal Magnetic Resonance of Glioblastoma Multiforme.

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. This drives research into optimization algorithms for treatment planning as well as radiofrequency (RF) applicator design for treatment delivery. In this work, nine clinically realistic GBM target volumes (TVs) for thermal intervention are compared using three optimization algorithms and up to ten RF applicator designs for thermal magnetic resonance. Hyperthermia treatment planning (HTP) was successfully performed for all cases, including very small, large, and even split target volumes. Minimum requirements formulated for the metrics assessing HTP outcome were met and exceeded for all patient specific cases. Results indicate a 16 channel two row arrangement to be most promising. HTP of TVs with a small extent in the cranial-caudal direction in conjunction with a large radial extent remains challenging despite the advanced optimization algorithms used. In general, deep seated targets are favorable. Overall, our findings indicate that a one-size-fits-all RF applicator might not be the ultimate approach in hyperthermia of brain tumors. It stands to reason that modular and reconfigurable RF applicator configurations might best suit the needs of targeting individual GBM geometry.

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.

Solving the Time- and Frequency-Multiplexed Problem of Constrained Radiofrequency Induced Hyperthermia.

Targeted radiofrequency (RF) heating induced hyperthermia has a wide range of applications, ranging from adjunct anti-cancer treatment to localized release of drugs. Focal RF heating is usually approached using time-consuming nonconvex optimization procedures or approximations, which significantly hampers its application. To address this limitation, this work presents an algorithm that recasts the problem as a semidefinite program and quickly solves it to global optimality, even for very large (human voxel) models. The target region and a desired RF power deposition pattern as well as constraints can be freely defined on a voxel level, and the optimum application RF frequencies and time-multiplexed RF excitations are automatically determined. 2D and 3D example applications conducted for test objects containing pure water (rtarget = 19 mm, frequency range: 500-2000 MHz) and for human brain models including brain tumors of various size (r1 = 20 mm, r2 = 30 mm, frequency range 100-1000 MHz) and locations (center, off-center, disjoint) demonstrate the applicability and capabilities of the proposed approach. Due to its high performance, the algorithm can solve typical clinical problems in a few seconds, making the presented approach ideally suited for interactive hyperthermia treatment planning, thermal dose and safety management, and the design, rapid evaluation, and comparison of RF applicator configurations.

Absolute Quantification of Phosphor-Containing Metabolites in the Liver Using 31 P MRSI and Hepatic Lipid Volume Correction at 7T Suggests No Dependence on Body Mass Index or Age.

BACKGROUND: Hepatic disorders are often associated with changes in the concentration of phosphorus-31 (31 P) metabolites. Absolute quantification offers a way to assess those metabolites directly but introduces obstacles, especially at higher field strengths (B0 ≥ 7T). PURPOSE: To introduce a feasible method for in vivo absolute quantification of hepatic 31 P metabolites and assess its clinical value by probing differences related to volunteers' age and body mass index (BMI). STUDY TYPE: Prospective cohort. SUBJECTS/PHANTOMS: Four healthy volunteers included in the reproducibility study and 19 healthy subjects arranged into three subgroups according to BMI and age. Phantoms containing 31 P solution for correction and validation. FIELD STRENGTH/SEQUENCE: Phase-encoded 3D pulse-acquire chemical shift imaging for 31 P and single-volume 1 H spectroscopy to assess the hepatocellular lipid content at 7T. ASSESSMENT: A phantom replacement method was used. Spectra located in the liver with sufficient signal-to-noise ratio and no contamination from muscle tissue, were used to calculate following metabolite concentrations: adenosine triphosphates (γ- and α-ATP); glycerophosphocholine (GPC); glycerophosphoethanolamine (GPE); inorganic phosphate (Pi ); phosphocholine (PC); phosphoethanolamine (PE); uridine diphosphate-glucose (UDPG); nicotinamide adenine dinucleotide-phosphate (NADH); and phosphatidylcholine (PtdC). Correction for hepatic lipid volume fraction (HLVF) was performed. STATISTICAL TESTS: Differences assessed by analysis of variance with Bonferroni correction for multiple comparison and with a Student's t-test when appropriate. RESULTS: The concentrations for the young lean group corrected for HLVF were 2.56 ± 0.10 mM for γ-ATP (mean ± standard deviation), α-ATP: 2.42 ± 0.15 mM, GPC: 3.31 ± 0.27 mM, GPE: 3.38 ± 0.87 mM, Pi : 1.42 ± 0.20 mM, PC: 1.47 ± 0.24 mM, PE: 1.61 ± 0.20 mM, UDPG: 0.74 ± 0.17 mM, NADH: 1.21 ± 0.38 mM, and PtdC: 0.43 ± 0.10 mM. Differences found in ATP levels between lean and overweight volunteers vanished after HLVF correction. DATA CONCLUSION: Exploiting the excellent spectral resolution at 7T and using the phantom replacement method, we were able to quantify up to 10 31 P-containing hepatic metabolites. The combination of 31 P magnetic resonance spectroscopy imaging data acquisition and HLVF correction was not able to show a possible dependence of 31 P metabolite concentrations on BMI or age, in the small healthy population used in this study. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:597-607.

Fluorine-19 MRI at 21.1 T: enhanced spin-lattice relaxation of perfluoro-15-crown-5-ether and sensitivity as demonstrated in ex vivo murine neuroinflammation.

OBJECTIVE: Fluorine MR would benefit greatly from enhancements in signal-to-noise ratio (SNR). This study examines the sensitivity gain of 19F MR that can be practically achieved when moving from 9.4 to 21.1 T. MATERIALS AND METHODS: We studied perfluoro-15-crown-5-ether (PFCE) at both field strengths (B0), as a pure compound, in the form of nanoparticles (NP) as employed to study inflammation in vivo, as well as in inflamed tissue. Brains, lymph nodes (LNs) and spleens were obtained from mice with experimental autoimmune encephalomyelitis (EAE) that had been administered PFCE NPs. All samples were measured at both B0 with 2D-RARE and 2D-FLASH using 19F volume radiofrequency resonators together. T1 and T2 of PFCE were measured at both B0 strengths. RESULTS: Compared to 9.4 T, an SNR gain of > 3 was observed for pure PFCE and > 2 for PFCE NPs at 21.1 T using 2D-FLASH. A dependency of 19F T1 and T2 relaxation on B0 was demonstrated. High spatially resolved 19F MRI of EAE brains and LNs at 21.1 T revealed signals not seen at 9.4 T. DISCUSSION: Enhanced SNR and T1 shortening indicate the potential benefit of in vivo 19F MR at higher B0 to study inflammatory processes with greater detail.

Millimeter spatial resolution in vivo sodium MRI of the human eye at 7 T using a dedicated radiofrequency transceiver array.

PURPOSE: The aim of this study was to achieve millimeter spatial resolution sodium in vivo MRI of the human eye at 7 T using a dedicated six-channel transceiver array. We present a detailed description of the radiofrequency coil design, along with electromagnetic field and specific absorption ratio simulations, data validation, and in vivo application. METHODS: Electromagnetic field and specific absorption ratio simulations were performed. Transmit field uniformity was optimized by using a multi-objective genetic algorithm. Transmit field mapping was conducted using a phase-sensitive method. An in vivo feasibility study was carried out with 3-dimensional density-adapted projection reconstruction imaging technique. RESULTS: Measured transmit field distribution agrees well with the one obtained from simulations. The specific absorption ratio simulations confirm that the radiofrequency coil is safe for clinical use. Our radiofrequency coil is light and conforms to an average human head. High spatial resolution (nominal 1.4 and 1.0 mm isotropic) sodium in vivo images of the human eye were acquired within scan times suitable for clinical applications (∼ 10 min). CONCLUSIONS: Three most important eye compartments in the context of sodium physiology were clearly delineated in all of the images: the vitreous humor, the aqueous humor, and the lens. Our results provide encouragement for further clinical studies. The implications for research into eye diseases including ocular melanoma, cataract, and glaucoma are discussed. Magn Reson Med 80:672-684, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Development of clinical simultaneous SPECT/MRI.

There is increasing clinical use of combined positron emission tomography and MRI, but to date there has been no clinical system developed capable of simultaneous single-photon emission computed tomography (SPECT) and MRI. There has been development of preclinical systems, but there are several challenges faced by researchers who are developing a clinical prototype including the need for the system to be compact and stationary with MRI-compatible components. The limited work in this area is described with specific reference to the Integrated SPECT/MRI for Enhanced stratification in Radio-chemo Therapy (INSERT) project, which is at an advanced stage of developing a clinical prototype. Issues of SPECT/MRI compatibility are outlined and the clinical appeal of such a system is discussed, especially in the management of brain tumour treatment.