Simulation studies promote technological development of radiofrequency phased array hyperthermia

A treatment planning program package for radiofrequency hyperthermia has been developed. It consists of software modules for processing three-dimensional computerized tomography (CT) data sets, manual segmentation, generation of tetrahedral grids, numerical calculation and optimisation of three-dimensional Ε field distributions using a volume surface integral equation algorithm as well as temperature distributions using an adaptive multilevel finite-elements code, and graphical tools for simultaneous representation of CT data and simulation results. Heat treatments are limited by hot spots in healthy tissues caused by Ε field maxima at electrical interfaces (bone/muscle). In order to reduce or avoid hot spots suitable objective functions are derived from power deposition patterns and temperature distributions, and are utilised to optimise antenna parameters (phases, amplitudes). The simulation and optimisation tools have been applied to estimate the improvements that could be reached by upgrades of the clinically used SIGMA-60 applicator (consisting of a single ring of four antenna pairs). The investigated upgrades are increased number of antennas and channels (triple-ring of 3 × 8 antennas and variation of antenna inclination. Significant improvement of index temperatures (1–2°C) is achieved by upgrading the single ring to a triple ring with free phase selection for every antenna or antenna pair. Antenna amplitudes and inclinations proved as less important parameters.     

Improving locoregional hyperthermia delivery using the 3-D controlled AMC-8 phased array hyperthermia system: A preclinical study

Background: The aim of this study is preclinical evaluation of our newly developed regional hyperthermia system providing 3-D SAR control: the AMC-8 phased array consisting of two rings, each with four 70 MHz waveguides. It was designed to achieve higher tumour temperatures and improve the clinical effectiveness of locoregional hyperthermia.

Methods: The performance of the AMC-8 system was evaluated with simulations and measurements aiming at heating a centrally located target region in rectangular (30 × 30 × 110 cm) and elliptical (36 × 24 × 80 cm) homogeneous tissue equivalent phantoms. Three properties were evaluated and compared to its predecessor, the 2-D AMC-4 single ring four waveguide array: (1) spatial control and (2) size of the SAR focus, (3) the ratio between maximum SAR outside the target region and SAR in the focus. Distance and phase difference between the two rings were varied.

Results: (1) Phase steering provides 3-D SAR control for the AMC-8 system. (2) The SAR focus is more elongated compared to the AMC-4 system, yielding a lower SAR level in the focus when using the same total power. This is counter-balanced by (3) a superficial SAR deposition which is half of that in the AMC-4 system, yielding a more favourable ratio between normal tissue and target SAR and allowing higher total power and up to 30% more SAR in the focus for 3 cm ring distance.

Conclusion: The AMC-8 system is capable of 3-D SAR control and its SAR distribution is more favourable than for the 2-D AMC-4 system. This result promises improvement in clinical tumour temperatures.     

Physical predictors of adequate hyperthermia with the annular phased array

One hundred and fifty-two hyperthermia sessions in 36 consecutive patients treated with the BSD 1000 annular phased array system (APAS) are reviewed with regard to physical predictors of quality of hyperthermia. Although central tumour temperatures exceeding 42°C were momentarily obtained in 62% of the sessions, it frequently proved difficult to maintain the patient at temperature for prolonged periods of time. The time to reach target temperature was negatively associated with quality of hyperthermia. Thus, of 25 sessions which required over 25 min to attain a temperature of 42°C, only one was adequate (defined as central tumour temperature ± 42°C maintained for at least 30 min) as opposed to 28/69 adequate sessions when 42 °C was reached in less than 25 min. Physical parameters measured in the first 3 min of the session found to be associated with adequate hyperthermia include an initial rate of temperature rise at the tumour site exceeding 0.4°C/min achieved with a net forward power less than 1500 W. Only three of 57 sessions not meeting these criteria were adequate. Treatment policy recommendations and recommendations for future research are made.     

Clinical integration of software tool VEDO for adaptive and quantitative application of phased array hyperthermia in the head and neck

Abstract

Background and purpose: In Rotterdam, patient-specific hyperthermia (HT) treatment planning (HTP) is applied for all deep head and neck (H&N) HT treatments. In this paper we introduce VEDO (the Visualisation Tool for Electromagnetic Dosimetry and Optimisation), the software tool required, and demonstrate its value for HTP-guided online complaint-adaptive (CA) steering based on specific absorption rate (SAR) optimisation during a H&N HT treatment.

Materials and methods: VEDO integrates CA steering, visualisation of the SAR patterns and mean tumour SAR (SAR_target) optimisation in a single screen. The pre-calculated electromagnetic fields are loaded into VEDO. During treatment, VEDO shows the SAR pattern, overlaid on the patients’ CT-scan, corresponding to the actually applied power settings and it can (re-)optimise the SAR pattern to minimise SAR at regions where the patient senses discomfort while maintaining a high SAR_target.

Results: The potential of the quantitative SAR steering approach using VEDO is demonstrated by analysis of the first treatment in which VEDO was used for two patients using the HYPERcollar.

These cases show that VEDO allows response to power-related complaints of the patient and to quantify the change in absolute SAR: increasing either SAR_target from 96 to 178?W/kg (case 1); or show that the first SAR distribution was already optimum (case 2).

Conclusion: This analysis shows that VEDO facilitates a quantitative treatment strategy allowing standardised application of HT by technicians of different HT centres, which will potentially lead to improved treatment quality and the possibility of tracking the effectiveness of different treatment strategies.     

Optimum excitation of phases and amplitudes in a phased array hyperthermia system

In order to achieve a desired temperature distribution inside and outside of malignant tissues, optimization techniques could be used in phased array hyperthermia systems to control effectively the amplitude and phase of the radiating elements. The optimization of a four-element phased array hyperthermia system operating at 432 MHz is examined theoretically. The proposed technique is based on a detailed physical model of the tissue medium to be heated in terms of both electromagnetic and thermal properties. A penalty function technique using a Newton method is applied to determine the optimum phases and amplitudes of the array. Several array geometrics have been studied and numerical results are presented.     

Design and characterisation of a phased antenna array for intact breast hyperthermia

Purpose: Currently available hyperthermia technology is not well suited to treating cancer malignancies in the intact breast. This study investigates a microwave applicator incorporating multiple patch antennas, with the goal of facilitating controllable power deposition profiles for treating lesions at diverse locations within the intact breast.

Materials and methods: A 3D-computational model was implemented to assess power deposition profiles with 915?MHz applicators incorporating a hemispheric groundplane and configurations of 2, 4, 8, 12, 16 and 20 antennas. Hemispheric breast models of 90?mm and 150?mm diameter were considered, where cuboid target volumes of 10?mm edge length (1?cm³) and 30?mm edge length (27?cm³) were positioned at the centre of the breast, and also located 15?mm from the chest wall. The average power absorption (αPA) ratio expressed as the ratio of the PA in the target volume and in the full breast was evaluated. A 4-antenna proof-of-concept array was fabricated and experimentally evaluated.

Results: Computational models identified an optimal inter-antenna spacing of 22.5° along the applicator circumference. Applicators with 8 and 12 antennas excited with constant phase presented the highest αPA at centrally located and deep-seated targets, respectively. Experimental measurements with a 4-antenna proof-of-concept array illustrated the potential for electrically steering power deposition profiles by adjusting the relative phase of the signal at antenna inputs.

Conclusions: Computational models and experimental results suggest that the proposed applicator may have potential for delivering conformal thermal therapy in the intact breast.     

Strategies for optimized application of annular-phased-array systems in clinical hyperthermia

A theoretical framework is presented for optimized heating of deep-seated tumours by phase and amplitude steering. The optimization problem for a specific tumour and perfusion case results in a functional dependency between power-level and maximum obtainable therapeutic efficiency. Different optimization criteria and strategies are outlined, which cause an increase of power or thermal dose in the tumour. Three tumour models (central pelvic tumour, eccentric abdominal tumour with or without necrosis) are analysed in detail. The simulation studies predict that appreciable parts of these tumours (50–100%) can be heated efficiently (42.5–43°C) within the range of available and clinically tolerated power levels (1–5 kW/m), if tumour perfusion is less than 20–25 ml/100 g min. Some improvements are obtained by increasing the number of independent channels (from four to eight) and by the application of time-dependent (complementary) power-deposition patterns.     

A practical system for clinical radiofrequency hyperthermia

This paper describes an apparatus for inducing local hyperthermis by passing high-frequency electrical currents through tissues between electrodes placed against the skin of the patient. The electrodes use a temperature-controlled saline solution contained by a thin rubber membrane to make contact. The resistivity of the saline solution is matched to that of body tissues. This yields a smooth transition from electrode to tissue, thereby greatly reducing the possibility of producing the skin burns which frequently appear along the edges of metallic electrodes. Use of the thin rubber membrane allows easy molding of a given set of electrodes to complex body contours for many different patients. The equipment has proven capable in clinical tests of heating bulky tumors in the head and neck and extremities without significant skin toxicity. Excessive beating of the subcutaneous fat, however, restricts the application of this heating method to tumors located in areas of the body with sparse adipose tissue.     

Evaluation of a dual-arm Archimedean spiral array for microwave hyperthermia

Purpose: This effort describes a third-party performance evaluation of a novel, commercial, dual-armed Archimedean spiral array hyperthermia applicator. The applicator is analysed for its ability to couple efficiently into muscle equivalent phantom loads, operate over a broad bandwidth to help accommodate variable tissue properties and generate predictable and repeatable SAR contours that are adaptable to clinically probable disease shapes.

Materials and methods: Characterization of the applicator includes E-field and return-loss measurements in liquid muscle tissue-equivalent phantom, as well as comparison of ‘treatment-planning’ simulations of several possible array SAR patterns with measured SAR from non-coherently driven spiral array antennae.

Results: The applicator demonstrates a reasonably low return loss over a large bandwidth and the ability to generate a very uniform heating pattern. Ability to adjust SAR contours spatially to fit specific shapes is also demonstrated.

Conclusions: This device should prove a welcome addition to a currently limited set of superficial heating applicators to provide controllable heating of superficial tissue disease.     

Benefits of superficial hyperthermia treatment planning: Five case studies

Purpose: To demonstrate the benefits of treatment planning in superficial hyperthermia.

Materials and methods: Five patient cases are presented, in which treatment planning was applied to troubleshoot treatment-limiting hotspots, to select the optimum applicator type and orientation, to assess the risk associated with metallic implants, to assess the feasibility of heating a deeper seated tumour, and to analyse the effective SAR coverage resulting from arrays of multiple incoherent applicators. FDTD simulation tools were used to investigate treatment options, either based on segmented or simplified anatomies.

Results: The background, approach and model implementation are presented per case. SAR cross-sections, profiles and isosurfaces are visualized to predict the effective SAR coverage of the target and the location of the maximum power absorption. In addition, the followed treatment strategy and the implications for the clinical treatment are given: for example, higher temperatures, relief of treatment limiting hot-spots or increased power input.

Conclusions: Treatment planning in superficial hyperthermia can be applied to improve clinical routine. Its application supports the selection of the optimum technique in non-standard cases, leading to direct benefits for the patient. In addition, treatment planning has shown to be an excellent tool for education and training for hyperthermia technicians and physicians.     

Conformal microwave array (CMA) applicators for hyperthermia of diffuse chest wall recurrence

Purpose: This article summarises the evolution of microwave array applicators for heating large area chest wall disease as an adjuvant to external beam radiation, systemic chemotherapy, and potentially simultaneous brachytherapy.

Methods: Current devices used for thermotherapy of chest wall recurrence are reviewed. The largest conformal array applicator to date is evaluated in four studies: (1) ability to conform to the torso is demonstrated with a CT scan of a torso phantom and MR scan of the conformal water bolus component on a mastectomy patient; (2) specific absorption rate (SAR) and temperature distributions are calculated with electromagnetic and thermal simulation software for a mastectomy patient; (3) SAR patterns are measured with a scanning SAR probe in liquid muscle phantom for a buried coplanar waveguide CMA; and (4) heating patterns and patient tolerance of CMA applicators are characterised in a clinical pilot study with 13 patients.

Results: CT and MR scans demonstrate excellent conformity of CMA applicators to contoured anatomy. Simulations demonstrate effective control of heating over contoured anatomy. Measurements confirm effective coverage of large treatment areas with no gaps. In 42 hyperthermia treatments, CMA applicators provided well-tolerated effective heating of up to 500 cm² regions, achieving target temperatures of T_min = 41.4 ± 0.7°C, T₉₀ = 42.1 ± 0.6°C, T_ave = 42.8 ± 0.6°C, and T_max = 44.3 ± 0.8°C as measured in an average of 90 points per treatment.

Conclusion: The CMA applicator is an effective thermal therapy device for heating large-area superficial disease such as diffuse chest wall recurrence. It is able to cover over three times the treatment area of conventional hyperthermia devices while conforming to typical body contours.     

Performance of a multi-sector ultrasound hyperthermia applicator and control system: in vivo studies

A multi-element ultrasound hyperthermia system (Labthermics Technologies, Inc., Sonotherm 1000) was utilized to deliver energy to two relatively well-defined regions (3 × 8 × 3 × 8 cm) on the lateral aspect of the right rear leg of 22 dogs in 1, 2 and 3 weekly treatments to a target temperature of 42–43°C, at a depth of 1 cm. The total treatment time was 30 min. One area heated on each dog was adjacent to the proximal femur and the other was 2–3 cm away from the distal aspect of the same bone. The system performed in an acceptably controlled manner and was able to deliver energy to a well-defined site. The mean temperature achieved, and rate of temperature rise in the heated regions, was independent of the region being treated. Little difference (0·12°C) was noted between the mean temperatures of the heated regions, and the temperature bounds (42–43°C) were exceeded by a small amount and for a relatively short period of time (out of range RMSE=0·6°C). Unheated regions showed much lower mean temperatures than did heated regions located 3 · 8 cm away, indicating that the energy was delivered in a well-defined manner. Superficial thermal injuries occurred in three of 22 dogs in the area heated 2–3 cm away from bone, and 11 of 22 dogs exhibited injuries in the tissue heated immediately adjacent to the femur.     

Radiofrequency hyperthermia: the design of coil transducers for local heating

Simple and complex coils have been designed and built for use as radiofrequency transducers for local and regional hyperthermia. The heating from such coils is produced by currents generated in the dielectric by the electromagnetic field radiated from the coil elements. The heating rate profile, as a function of phantom depth, is dependent upon the size and geometry of the coil, its proximity to the dielectric, and the transducer current. Since the fields of simple pancake coils are inhomogeneous, either complex geometries or some method of smoothing is required. A simple solution is to move the coil over the region to be heated or to use multiple applicators. However, many satisfactory heating patterns have been derived for stationary coils designed to heat well-defined subcutaneous volumes to a depth of 3-5 cm. Thermometry studies in static saline-gelatin phantoms demonstrate extensive heating ranges and flexibility since the coils couple with the dielectric through air.     

A multi-element ultrasonic hyperthermia applicator with independent element control

Acoustic field patterns from a planar multi-element ultrasonic applicator were determined experimentally and compared with theory. Measurements were obtained from square arrays of 4 and 16 elements. The acoustic fields produced by various configurations of individual square elements (3 × 6 cm × 3–6 cm) driven at 1 MHz were measured in water. Transverse and axial scans paths were used to characterize the acoustic beam for different aperture sizes and individual element excitations. Unequal power excitation of adjacent elements produced multiple peaked acoustic intensity patterns. While a simple theoretical model was not able to account for all the experimentally determined transverse and axial field patterns, a model including mechanical damping improved the agreement between theory and experiment. However, less ripple in the axial pattern was measured than predicted by either theoretical model. The ability of the applicator to generate acoustic field patterns suitable for local tissue heating was demonstrated by an experimental study in dog thigh muscle.     

A literature survey on indicators for characterisation and optimisation of SAR distributions in deep hyperthermia,a plea for standardisation

Purpose: To evaluate the predictive value of SAR indicators by assessing the correlation of a SAR indicator with the corresponding predicted temperature. Ultimately, this should lead to a number of verified SAR indicators for characterization and optimization of a predicted SAR distribution.

Methods: A literature survey is followed by an evaluation of the SAR indicators on their functionality, using a set of heuristic classification criteria. To obtain an objective assessment of the predictive value for SAR characterisation, all SAR indicators are evaluated by correlating the value of the SAR indicator to the predicted target temperature when heated with the BSD2000 Sigma 60 applicator. Two methods were followed. First, the specificity of the SAR indicator to target temperature was assessed for each of the 36 patient-specific models, using 30 randomly chosen phase and amplitude settings. Secondly, each SAR indicator was used as a goal function to assess its suitability for optimisation purposes.

Results: Only a selected number of SAR indicators correlate well with tumour/target-temperature. Hence, for target-related properties, an adequate set of SAR indicators is found in the literature. For hotspots, modifications are desirable. For optimisation purposes, improved objective functions have been defined.

Conclusions: From the correlation of the SAR indicators with tumour temperature, a preferred set of SAR indicators is derived:

• For target heating, ‘average SAR ratio’, ‘Hotspot-target SAR ratio’, and ‘homogeneity coefficient’ provide suitable objective criteria, while for hotspot reduction, ‘Hotspot-target SAR ratio’ is considered the most useful indicator.

• For optimisation procedures, ‘Hotspot-target SAR ratio’ is currently the most suitable objective function.

     

Optimisation-based thermal treatment planning for catheter-based ultrasound hyperthermia

A patient-specific optimisation-based hyperthermia treatment planning program for catheter-based ultrasound technology was developed for a priori evaluation of proposed applicator implant strategies and determination of initial applied power settings. The interstitial and endocavity heating applicators, designed for delivering 3-D controllable hyperthermia within High Dose Rate (HDR) brachytherapy implants, consist of linear and sectored arrays of ultrasound transducers with variable power control in both length and angle. A 3D biothermal model, which incorporates relevant anatomical structures and implant geometries based upon HDR treatment planning, has been developed to simulate the temperature distributions induced by these ultrasound applicators within the catheter implants. A temperature-based constrained optimisation algorithm was devised and integrated within the finite-element thermal solver to determine the optimal applied power levels. A temperature-expressed objective function and constraints were employed to limit maximum temperature (T_max), maximise target coverage (T_target), and minimise thermal exposure to normal tissue and surrounding organs. The optimisation-based treatment planning was applied on representative examples of clinical HDR implants for endocavity treatment of cervix (n = 3) and interstitial treatment of prostate (n = 3). Applicator positioning and orientation, T_max, and T_target, were varied, and temperature volume and thermal dose volume histograms calculated for each plan. The optimisation approach provided optimal applied power levels (4–24 independent transducer sections) leading to conforming or tailored temperature distributions for all cases, as indicated with improved temperature index T₉₀ in the target volume and negligible temperature and thermal dose (t_43,max < 1 min) exposure in surrounding non-targeted tissues, such as bladder and rectum. The precision of the optimised power estimates was shown to be within <5% for a range of starting levels and were similarly convergent. The execution times of this optimisation (<16 min) and forward thermal treatment planning (<22 min) is sufficiently fast to be integrated into the clinical setting. This optimisation-based treatment planning platform for catheter-based ultrasound applicators is a useful tool to provide feedback for applicator selection (sector angle, number of transducer sections along length), positioning (angle or orientation), optimal initial power settings, and has potential to significantly improve the delivery of hyperthermia in conjunction with HDR brachytherapy.     

Metamaterial lens applicator for microwave hyperthermia of breast cancer

Artificial left-handed metamaterial (LHM) provides a new perspective for microwave hyperthermia. Four flat LHM slab lenses can be used to form a focus-flexible applicator for breast tumour hyperthermia. By adjusting microwave sources behind the four flat LHM lenses, microwaves emitted from the sources can be focused tightly at different points in the breast tissue so that necessary heating depth in breast tissue can be achieved. Numerical simulations with a two-dimensional finite-difference time-domain method indicate that hyperthermia with the proposed four-lens applicator of moderate LHM losses could be effective in achieving desired power deposition in a heterogeneous breast model. Temperature distribution obtained by solving the bio-heat transfer equation demonstrates that temperature above 43°C can be maintained in the tumour volume for specific periods of time. Flat slab LHM lenses offer a feasible alternative to traditional mechanically scanned lens applicator and electronically scanned phased-array applicators.     

Characteristics and performance evaluation of the capacitive Contact Flexible Microstrip Applicator operating at 70 MHz for external hyperthermia

Purpose: To characterise and evaluate the capacitive Contact Flexible Microstrip Applicator operating at 70 MHz, CFMA-70. This applicator is introduced for the treatment of superficial tumours with extension in depth beyond the range of regular superficial applicators.

Methods: E-field measurements were performed in an elliptical phantom filled with a saline solution using an E-field vector probe. E-field distributions and SAR patterns are compared to those of the CFMA-434 and of 70 MHz waveguides. The applicator has been used for the treatment of 6 patients with breast cancer with a tumour depth exceeding 4 cm.

Results: The effective heating depth of the CFMA-70 is 50% larger than for the CFMA-434. Its effective field size is 26 × 20 cm (aperture 29 × 20 cm), larger than for an equally sized CFMA-434. In contrast to the CFMA-434 the SAR pattern of this applicator is insensitive to the bolus thickness. Comparison to 70 MHz waveguides shows that the E-field component normal to the applicator is 100% larger for the CFMA-70. During clinical applications acceptable temperatures were realised for individual sessions (also at depth), but in many cases treatment limiting hot spots occurred close to superficial bony structures near the applicator edge. Both surface irregularities and the normal field component may be responsible.

Conclusions: The CFMA-70 has adequate penetration depth for the treatment of superficial tumours exceeding a depth of 4 cm. However, the relatively large normal E-field component may induce treatment-limiting hot spots at tissue interfaces in the direction normal to the applicator's surface.     

Steering in locoregional deep hyperthermia: Evaluation of common practice with 3D-planning

Purpose: In Rotterdam, fifteen years of clinical experience with deep hyperthermia has sublimated in empirical treatment guidelines. In this paper, a hyperthermia treatment planning system (HTPS) is employed to investigate the effect of these guidelines on global power distribution, their effectiveness and the rationale behind each guideline.

Materials and methods: Four guidelines were investigated. The first two prescribe steering actions for balancing intraluminal temperatures and alleviating complaints of deep-seated pain or pressure. The third guideline handles superficial complaints of pain or heat sensation. The last guideline states that frequency should be increased from 77 MHz upwards in case of multiple, opposite, painful regions uncontrollable by the previous steering actions.

For all steering actions it is assumed that input power is increased until complaints occur. Sigma Hyperplan was used to calculate specific absorption rate (SAR) distributions for five patient models with locally advanced cervical cancer. Absorbed power ratios of different regions of interest were evaluated to illustrate steering efficacy and complaint reduction.

Results and conclusions: Phase steering is effective in shifting the central power distribution to the periphery, and is an appropriate method to balance temperatures or to handle deep-seated complaints. Reduction of amplitude is the proper action to alleviate superficial complaints of heat or pressure. Compression of the SAR distribution, mainly in the lateral direction, is predicted with increasing frequency. Hence, for complaints in the lower back or on the sides, a frequency increase should be considered.

We conclude that the results of the HTPS are in close agreement with the empirical steering guidelines.     

Stanford 3D hyperthermia treatment planning system. Technical review and clinical summary

In the field of deep regional hyperthermia cancer therapy the Sigma 60 applicator of the BSD-2000 Hyperthermia System is one of the most widely used devices. This device employs four independent sources of radiofrequency electromagnetic energy to heat tumour sites deep within the body. The difficulty in determining the input parameters for the four sources has motivated the development of a computer-based three-dimensional (3D) treatment planning system. The Stanford 3D Hyperthermia Treatment Planning System has been in clinical use at Stanford Medical Center for the past 2 years. It utilizes a patient-specific, three-dimensional computer simulation to determine safe and effective power deposition plans. An optimization programme for the selection of the amplitudes, phases and frequency for the sources has been developed and used in the clinic. Examples of the application of the treatment planning for hyperthermia treatment of pulmonary, pelvic, and mediastinal tumours are presented. Methods for quantifying the relative effectiveness of various treatment plans are reviewed.