Development of a Clinical Head and Neck Hyperthermia Applicator

Treatment of advanced tumours in the head and neck (H&N) remains complex and the toxicity related to the currently standard treatment modalities is a major issue. For many tumour sites, the addition of hyperthermia (HT) to radiotherapy has been shown to result in improved local control rates and/or better overall survival rates. HT has a high potential to improve cancer treatment results in H&N patients as well without adding toxicity. However, an appropriate applicator that can heat both superficially and deeply located target sites in the H&N region is currently not available. This thesis describes the items that needed to be addressed to design and build such an applicator. Extensive theoretical parameters studies were performed 1) to show the feasibility of deep heating in the H&N using radiofrequency (RF) waves and 2) to guide the design of the applicator. These parameter studies were performed using electromagnetic (EM) simulation programs. The predictions were then verified by measurements and with their results we designed and build a clinical prototype (the HYPERcollar applicator). We performed treatment planning for several patients to establish the specific absorption rate (SAR) patterns that are achievable with this applicator. In a heating session of the first patient of an ongoing clinical feasibility study we showed the possibility of deep heating using the HYPERcollar applicator

An Electromagnetic Head and Neck Hyperthermia Applicator: experimental phantom verification and FDTD model

Purpose: To experimentally verify the feasibility of focused heating in the neck region by an array of two rings of six electromagnetic antennas. We also measured the dynamic specific absorption rate (SAR) steering possibilities of this setup and compared these SAR patterns to simulations. Methods and Materials: Using a specially constructed laboratory prototype head-and-neck applicator, including a neck-mimicking cylindrical muscle phantom, we performed SAR measurements by electric field, Schottkydiode sheet measurements and, using the power-pulse technique, by fiberoptic thermometry and infrared thermography. Using phase steering, we also steered the SAR distribution in radial and axial directions. All measured distributions were compared with the predictions by a finite-difference time-domain–based electromagnetic simulator. Results: A central 50% iso-SAR focus of 35 +/- 3 mm in diameter and about 100 +/- 15 mm in length was obtained for all investigated settings. Furthermore, this SAR focus could be steered toward the desired location in the radial and axial directions with an accuracy of ~5 mm. The SAR distributions as measured by all three experimental methods were well predicted by the simulations. Conclusion: The results of our study have shown that focused heating in the neck is feasible and that this focus can be effectively steered in the radial and axial directions. For quality assurance measurements, we believe that the Schottky-diode sheet provides the best compromise among effort, speed, and accuracy, although a more specific and improved design is warranted

A head and neck hyperthermia applicator: Theoretical antenna array design

Purpose: Investigation into the feasibility of a circular array of dipole antennas to deposit RF-energy centrally in the neck as a function of: (1) patient positioning, (2) antenna ring radius, (3) number of antenna rings, (4) number of antennas per ring and (5) distance between antenna rings. Materials and Methods: Power absorption (PA) distributions in realistic, head and neck, anatomy models are calculated at 433 MHz. Relative PA distributions corresponding to different set-ups were analysed using the ratio of the average PA (aPA) in the target and neck region. Results: Enlarging the antenna ring radius from 12.5cm to 25 cm resulted in a ~21% decrease in aPA. By changing the orientation of the patients with respect to the array an increase by ~11% was obtained. Increase of the amount of antenna rings led to a better focussing of the power (1 - 2 / 3: ~17%). Increase of the distance between the antenna rings resulted in a smaller (more target region conformal) focus but also a decreased power penetration. Conclusions: A single optimum array setup suitable for all patients is difficult to define. Based on the results and practical limitations a setup consisting of two rings of six antennas with a radius of 20 cm and 6 cm array spacing is considered a good choice providing the ability to heat the majority of patients

A Patch Antenna Design for Application in a Phased-Array Head and Neck Hyperthermia Applicator

In this paper, we describe a specifically designed patch antenna that can be used as the basis antenna element of a clinical phased-array head and neck hyperthermia applicator. Using electromagnetic simulations we optimized the dimensions of a probe-fed patch antenna design for operation at 433 MHz. By several optimization steps we could converge to a theoretical reflection of -38 dB and a bandwidth (-15 dB) of 20 MHz (4.6%). Theoretically, the electrical performance of the antenna was satisfactory over a temperature range of 15 C–35 C, and stable for patient-antenna distances to as low as 4 cm. In an experimental cylindrical setup using six elements of the final patch design, we measured the impedance characteristics of the antenna 1) to establish its performance in the applicator and 2) to validate the simulations. For this experimental setup we simulated and measured comparable values: -21 dB reflection at 433 MHz and a bandwidth of 18.5 MHz. On the basis of this study, we anticipate good central interference of the fields of multiple antennas and conclude that this patch antenna design is very suitable for the clinical antenna array. In future research we will verify the electrical performance in a prototype applicator

The potential of adjusting water bolus liquid properties for economic and precise MR thermometry guided radiofrequency hyperthermia

The potential of MR thermometry (MRT) fostered the development of MRI compatible radiofrequency (RF) hyperthermia devices. Such device integration creates major technological challenges and a crucial point for image quality is the water bolus (WB). The WB is located between the patient body and external sources to both couple electromagnetic energy and to cool the patient skin. However, the WB causes MRT errors and unnecessarily large field of view. In this work, we studied making the WB MRI transparent by an optimal concentration of compounds capable of modifying T2 * relaxation without an impact on the efficiency of RF heating. Three different T2 * reducing compounds were investigated, namely CuSO4, MnCl2, and Fe3 O4. First, electromagnetic properties and T2 * relaxation rates at 1.5 T were measured. Next, through multi-physics simulations, the predicted effect on the RF-power deposition pattern was evaluated and MRT precision was experimentally assessed. Our results identified 5 mM Fe3 O4 solution as optimal since it does not alter the RF-power level needed and improved MRT precision from 0.39◦ C to 0.09◦ C. MnCl2 showed a similar MRT improvement, but caused unacceptable RF-power losses. We conclude that adding Fe3 O4 has significant potential to improve RF hyperthermia treatment monitoring under MR guidance

Assessment of the local SAR Distortion by Major Anatomical Structures in a Cylindrical Neck Phantom

The objective of this work is to gain insight in the distortions on the local SAR distribution by various major anatomical structures in the neck. High resolution 3D FDTD calculations based on a variable grid are made for a semi-3D generic phantom based on average dimensions obtained from CT-derived human data and in which simplified structures representing trachea, cartilage, spine and spinal cord are inserted. In addition, phantoms with dimensions equal to maximum and minimum values within the CT-derived data are also studied. In all cases, the phantoms are exposed to a circular coherent array of eight dipoles within a water bolus and driven at 433 MHz. Comparisons of the SAR distributions due to individual structures or a combination of structures are made relative to a cylindrical phantom with muscle properties. The calculations predict a centrally located region of high SAR within all neck phantoms. This focal region, expressed as contours at either 50% or 75% of the peak SAR, changes from a circular cross-section in the case of the muscle phantom to a doughnut shaped region when the anatomical structures are present. The presence of the spine causes the greatest change in the SAR distribution, followed closely by the trachea. Global changes in the mean SAR relative to the uniform phantom are <11%, whilst local changes are as high as 2.7-fold. There is little difference in the focal dimensions between the average and smallest phantoms, but a decrease in the focal region is seen in the case of the largest phantom. This study presents a first step towards understanding of the complex influences of the various parameters on the SAR pattern which will facilitate the design of a site-specific head and neck hyperthermia applicator

SAR thresholds for electromagnetic exposure using functional thermal dose limits

Background and purpose: To protect against any potential adverse effects to human health from localised exposure to radio frequency (100 kHz–3 GHz) electromagnetic fields (RF EMF), international health organisations have defined basic restrictions on specific absorption rate (SAR) in tissues. These exposure restrictions incorporate safety factors which are generally conservative so that exposures that exceed the basic restrictions are not necessarily harmful. The magnitude of safety margin for various exposure scenarios is unknown. This shortcoming becomes more critical for medical applications where the safety guidelines are required to be relaxed. The purpose of this study was to quantify the magnitude of the safety factor included in the current basic restrictions for various exposure scenarios under localised exposure to RF EMF. Materials and methods: For each exposure scenario, we used the lowest thermal dose (TD) required to induce acute local tissue damage reported in literature, calculated the corresponding TD-functional SAR limits (SARTDFL) and related these limits to the existing basic restrictions, thereby estimating the respective safety factor. Results: The margin of safety factor in the current basic restrictions on 10 g peak spatial average SAR (psSAR10g) for muscle is large and can reach up to 31.2. Conclusions: Our analysis provides clear instructions for calculation of SARTDFL and consequently quantification of the incorporated safety factor in the current basic restrictions. This research can form the basis for further discussion on establishing the guidelines dedicated to a specific exposure scenario, i.e. exposure-specific SAR limits, rather than the current generic guidelines

Intrasubject multimodal groupwise registration with the conditional template entropy

Image registration is an important task in medical image analysis. Whereas most methods are designed for the registration of two images (pairwise registration), there is an increasing interest in simultaneously aligning more than two images using groupwise registration. Multimodal registration in a groupwise setting remains difficult, due to the lack of generally applicable similarity metrics. In this work, a novel similarity metric for such groupwise registration problems is proposed. The metric calculates the sum of the conditional entropy between each image in the group and a representative template image constructed iteratively using principal component analysis. The proposed metric is validated in extensive experiments on synthetic and intrasubject clinical image data. These experiments showed equivalent or improved registration accuracy compared to other state-of-the-art (dis)similarity metrics and improved transformation consistency compared to pairwise mutual information

A three-layer MRI-based head phantom for experimental validation of tES simulations

Transcranial electric stimulation (tES) is being investigated for the relief of seizures in medically refractory epilepsy patients. In a quest to optimize the electrode placement and current for improvement of the outcome, we are investigating the exploitation of the pre-stimulation planning using finite element simulations based on individual anatomy from MRI [RM1] scans. A crucial step is validating the stimulation modeling accuracy, but commercial setups for validation do not exist.Hereto, we developed a three-layer head phantom, consisting of skin, skull, and brain tissue, that captures the crucial anatomical features and provides a convenient way of verifying the induced electric fields. It also enables systematic characterization of the uncertainties and variations in conductivity and anatomy. Experiments on the three-layer phantom bridge the gap between simulations and clinical practice since they also allow for using clinical hardware and electrodes.The developed phantom consists of an agar and salt brain layer, a graphite-doped polyurethane skull, and a skin layer made from agar gel with a different conductivity. In this way the solid skull separates the two gel layers, preventing possible ion drift over the layers. The anatomy is based on the ICBM 152 linear model, an average of 152 MRI scans, which enables us to intuitively link measurements and simulations. To perform the systematic characterization experiments, hardware and software were designed in-house. This allows for stimulations and measurements on the phantom in a cheap and modular way. The designed hardware consists of a PID-controlled tES stimulator, which can deliver 4 mA with a frequency up to 100 Hz, and a four-channel differential sensing board based on the OpenBCI Ganglion board.A realistic and modular phantom expands the possibilities of preclinical tES research by providing a tool to validate electric field simulations as well as experiment with clinical hardware and anatomical variations

Systematic review of pre-clinical and clinical devices for magnetic resonance-guided radiofrequency hyperthermia

Clinical trials have demonstrated the therapeutic benefits of adding radiofrequency (RF) hyperthermia (HT) as an adjuvant to radio- and chemotherapy. However, maximum utilization of these benefits is hampered by the current inability to maintain the temperature within the desired range. RF HT treatment quality is usually monitored by invasive temperature sensors, which provide limited data sampling and are prone to infection risks. Magnetic resonance (MR) temperature imaging has been developed to overcome these hurdles by allowing noninvasive 3D temperature monitoring in the target and normal tissues. To exploit this feature, several approaches for inserting the RF heating devices into the MR scanner have been proposed over the years. In this review, we summarize the status quo in MR-guided RF HT devices and analyze trends in these hybrid hardware configurations. In addition, we discuss the various approaches, extract best practices and identify gaps regarding the experimental validation procedures for MR - RF HT, aimed at converging to a common standard in this process