Quality assurance guidelines for interstitial hyperthermia.

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical hyperthermia treatments and trials. This document outlines the clinical and technical consequences of the specific properties of interstitial heat delivery and specifies recommendations for hyperthermia administration with interstitial techniques. Interstitial hyperthermia aims at tumor temperatures in the 40-44 °C range as an adjunct to radiation or chemotherapy. The clinical part of this document imparts specific clinical experience of interstitial heat delivery to various tumor sites as well as recommended interstitial hyperthermia workflow and procedures. The second part describes technical requirements for quality assurance of current interstitial heating equipment including electromagnetic (radiative and capacitive) and ultrasound heating techniques. Detailed instructions are provided on characterization and documentation of the performance of interstitial hyperthermia applicators to achieve reproducible hyperthermia treatments of uniform high quality. Output power and consequent temperature rise are the key parameters for characterization of applicator performance in these QA guidelines. These characteristics determine the specific maximum tumor size and depth that can be heated adequately. The guidelines were developed by the ESHO Technical Committee with participation of senior STM members and members of the Atzelsberg Circle.

Dielectric properties measurements of brown and white adipose tissue in rats from 0.5 to 10 GHz.

Brown adipose tissue (BAT) plays an important role in whole body metabolism and with appropriate stimulus could potentially mediate weight gain and insulin sensitivity. Although imaging techniques are available to detect subsurface BAT, there are currently no viable methods for continuous acquisition of BAT energy expenditure. Microwave (MW) radiometry is an emerging technology that allows the quantification of tissue temperature variations at depths of several centimeters. Such temperature differentials may be correlated with variations in metabolic rate, thus providing a quantitative approach to monitor BAT metabolism. In order to optimize MW radiometry, numerical and experimental phantoms with accurate dielectric properties are required to develop and calibrate radiometric sensors. Thus, we present for the first time, the characterization of relative permittivity and electrical conductivity of brown (BAT) and white (WAT) adipose tissues in rats across the MW range 0.5-10GHz. Measurements were carried out in situ and post mortem in six female rats of approximately 200g. A Cole-Cole model was used to fit the experimental data into a parametric model that describes the variation of dielectric properties as a function of frequency. Measurements confirm that the dielectric properties of BAT (εr = 14.0-19.4, σ = 0.3-3.3S/m) are significantly higher than those of WAT (εr = 9.1-11.9, σ = 0.1-1.9S/m), in accordance with the higher water content of BAT.

Current state of the art of regional hyperthermia treatment planning: a review.

Locoregional hyperthermia, i.e. increasing the tumor temperature to 40-45 °C using an external heating device, is a very effective radio and chemosensitizer, which significantly improves clinical outcome. There is a clear thermal dose-effect relation, but the pursued optimal thermal dose of 43 °C for 1 h can often not be realized due to treatment limiting hot spots in normal tissue. Modern heating devices have a large number of independent antennas, which provides flexible power steering to optimize tumor heating and minimize hot spots, but manual selection of optimal settings is difficult. Treatment planning is a very valuable tool to improve locoregional heating. This paper reviews the developments in treatment planning software for tissue segmentation, electromagnetic field calculations, thermal modeling and optimization techniques. Over the last decade, simulation tools have become more advanced. On-line use has become possible by implementing algorithms on the graphical processing unit, which allows real-time computations. The number of applications using treatment planning is increasing rapidly and moving on from retrospective analyses towards assisting prospective clinical treatment strategies. Some clinically relevant applications will be discussed.

Study of the one dimensional and transient bioheat transfer equation: multi-layer solution development and applications.

In this work we derive an analytical solution given by Bessel series to the transient and one-dimensional (1D) bioheat transfer equation in a multi-layer region with spatially dependent heat sources. Each region represents an independent biological tissue characterized by temperature-invariant physiological parameters and a linearly temperature dependent metabolic heat generation. Moreover, 1D Cartesian, cylindrical or spherical coordinates are used to define the geometry and temperature boundary conditions of first, second and third kinds are assumed at the inner and outer surfaces. We present two examples of clinical applications for the developed solution. In the first one, we investigate two different heat source terms to simulate the heating in a tumor and its surrounding tissue, induced during a magnetic fluid hyperthermia technique used for cancer treatment. To obtain an accurate analytical solution, we determine the error associated with the truncated Bessel series that defines the transient solution. In the second application, we explore the potential of this model to study the effect of different environmental conditions in a multi-layered human head model (brain, bone and scalp). The convective heat transfer effect of a large blood vessel located inside the brain is also investigated. The results are further compared with a numerical solution obtained by the Finite Element Method and computed with COMSOL Multiphysics v4.1©.

DESIGN OF MEDICAL RADIOMETER FRONT-END FOR IMPROVED PERFORMANCE.

We have investigated the possibility of building a singleband Dicke radiometer that is inexpensive, small-sized, stable, highly sensitive, and which consists of readily available microwave components. The selected frequency band is at 3.25-3.75 GHz which provides a reasonable compromise between spatial resolution (antenna size) and sensing depth for radiometry applications in lossy tissue. Foreseen applications of the instrument are non-invasive temperature monitoring for breast cancer detection and temperature monitoring during heating. We have found off-the-shelf microwave components that are sufficiently small (< 5 mm × 5 mm) and which offer satisfactory overall sensitivity. Two different Dicke radiometers have been realized: one is a conventional design with the Dicke switch at the front-end to select either the antenna or noise reference channels for amplification. The second design places a matched pair of low noise amplifiers in front of the Dicke switch to reduce system noise figure.Numerical simulations were performed to test the design concepts before building prototype PCB front-end layouts of the radiometer. Both designs provide an overall power gain of approximately 50 dB over a 500 MHz bandwidth centered at 3.5 GHz. No stability problems were observed despite using triple-cascaded amplifier configurations to boost the thermal signals. The prototypes were tested for sensitivity after calibration in two different water baths. Experiments showed superior sensitivity (36% higher) when implementing the low noise amplifier before the Dicke switch (close to the antenna) compared to the other design with the Dicke switch in front. Radiometer performance was also tested in a multilayered phantom during alternating heating and radiometric reading. Empirical tests showed that for the configuration with Dicke switch first, the switch had to be locked in the reference position during application of microwave heating to avoid damage to the active components (amplifiers and power meter). For the configuration with a low noise amplifier up front, damage would occur to the active components of the radiometer if used in presence of the microwave heating antenna. Nevertheless, this design showed significantly improved sensitivity of measured temperatures and merits further investigation to determine methods of protecting the radiometer for amplifier first front ends.

Non-invasive vesicoureteral reflux detection: heating risk studies for a new device.

OBJECTIVE: To investigate a novel non-invasive device developed to warm bladder urine and to measure kidney temperature to detect vesicoureteral reflux. MATERIALS AND METHODS: Microwave antennas focused energy within the bladder. Phantom experiments measured the results. The heating protocol was optimized in an in-vivo porcine model, and then tested once, twice and three times consecutively in three pigs followed by pathologic examinations. RESULTS: Computer simulations showed a dual concentric conductor square slot antenna to be the best. Phantom studies revealed that this antenna easily heated a bladder phantom without over heating intervening layers. In-vivo a bladder heating protocol of 3 min with 30 W each to two adjacent antennas 45 s on 15 s off followed by 15 min of 15 s on and 45 s off was sufficient. When pigs were heated once, twice and three times with this heating protocol, pathologic examination of all tissues in the heated area showed no thermal changes. More intensive heating in the animal may have resulted in damage to muscle fibers in the anterior abdominal wall. CONCLUSIONS: Selective warming of bladder urine was successfully demonstrated in phantom and animals. Localized heating for this novel vesicoureteral reflux device requires low-power levels and should be safe for humans.

EVOLUTION OF ANTENNA PERFORMANCE FOR APPLICATIONS IN THERMAL MEDICNE.

This presentation provides an overview of electromagnetic heating technology that has proven useful in clinical applications of hyperthermia therapy for cancer. Several RF and microwave antenna designs are illustrated which highlight the evolution of technology from simple waveguide antennas to spatially and temporally adjustable multiple antenna phased arrays for deep heating, conformal arrays for superficial heating, and compatible approaches for radiometric and magnetic resonance image based non-invasive thermal monitoring. Examples of heating capabilities for several recently developed applicators demonstrate highly adjustable power deposition that has not been possible in the past.

Thermal characteristics of thermobrachytherapy surface applicators for treating chest wall recurrence.

The aim of this study was to investigate temperature and thermal dose distributions of thermobrachytherapy surface applicators (TBSAs) developed for concurrent or sequential high dose rate (HDR) brachytherapy and microwave hyperthermia treatment of chest wall recurrence and other superficial diseases. A steady-state thermodynamics model coupled with the fluid dynamics of a water bolus and electromagnetic radiation of the hyperthermia applicator is used to characterize the temperature distributions achievable with TBSAs in an elliptical phantom model of the human torso. Power deposited by 915 MHz conformal microwave array (CMA) applicators is used to assess the specific absorption rate (SAR) distributions of rectangular (500 cm(2)) and L-shaped (875 cm(2)) TBSAs. The SAR distribution in tissue and fluid flow distribution inside the dual-input dual-output (DIDO) water bolus are coupled to solve the steady-state temperature and thermal dose distributions of the rectangular TBSA (R-TBSA) for superficial tumor targets extending 10-15 mm beneath the skin surface. Thermal simulations are carried out for a range of bolus inlet temperature (T(b) = 38-43 degrees C), water flow rate (Q(b) = 2-4 L min(-1)) and tumor blood perfusion (omega(b) = 2-5 kg m(-3) s(-1)) to characterize their influence on thermal dosimetry. Steady-state SAR patterns of the R- and L-TBSA demonstrate the ability to produce conformal and localized power deposition inside the tumor target sparing surrounding normal tissues and nearby critical organs. Acceptably low variation in tissue surface cooling and surface temperature homogeneity was observed for the new DIDO bolus at a 2 L min(-1) water flow rate. Temperature depth profiles and thermal dose volume histograms indicate bolus inlet temperature (T(b)) to be the most influential factor on thermal dosimetry. A 42 degrees C water bolus was observed to be the optimal choice for superficial tumors extending 10-15 mm from the surface even under significant blood perfusion. Lower bolus temperature may be chosen to reduce the thermal enhancement ratio (TER) in the most sensitive skin where maximum radiation dose is delivered and to extend the thermal enhancement of radiation dose deeper. This computational study indicates that well-localized elevation of tumor target temperature to 40-44 degrees C can be accomplished by large surface-conforming TBSAs using appropriate selection of coupling bolus temperature.

Design of Small-sized and Low-cost Front End to Medical Microwave Radiometer.

We have investigated the possibility of building a Dicke radiometer that is inexpensive, small-sized, stable, high sensitivity and consists of readily available microwave components. The selected frequency band is at 3-4 GHz and can be used for breast cancer detection, with sufficient spatial resolution. We have found microwave components that are small (< 5mm × 5 mm) and provide sufficient sensitivity. We have built two different Dicke radiometers: One is of conventional design with Dicke switch at front end to select antenna or noise rererence and the other with a low noise amplifier before the Dicke Switch. We have tested this concept with simulations and built prototypes. The two designs provide a gain of approximately 50 dB, and bandwidth of about 500 MHz. One of the designs has a stability µ > 1 and the other design provide instability µ < 1 for a part of the pass band. The prototypes are tested for sensitivity after calibration in two different known temperature waterbaths. The results show that the design with the low noise amplifier before the Dicke switch has 36% higher sensitivity than the other design with Dicke switch in front.

Characterization of a digital microwave radiometry system for noninvasive thermometry using a temperature-controlled homogeneous test load.

Microwave radiometry has been proposed as a viable noninvasive thermometry approach for monitoring subsurface tissue temperatures and potentially controlling power levels of multielement heat applicators during clinical hyperthermia treatments. With the evolution of technology, several analog microwave radiometry devices have been developed for biomedical applications. In this paper, we describe a digital microwave radiometer with built-in electronics for signal processing and automatic self-calibration. The performance of the radiometer with an Archimedean spiral receive antenna is evaluated over a bandwidth of 3.7-4.2 GHz in homogeneous and layered water test loads. Controlled laboratory experiments over the range of 30-50 degrees C characterize measurement accuracy, stability, repeatability and penetration depth sensitivity. The ability to sense load temperature through an intervening water coupling bolus of 6 mm thickness is also investigated. To assess the clinical utility and sensitivity to electromagnetic interference (EMI), experiments are conducted inside standard clinical hyperthermia treatment rooms with no EM shielding. The digital radiometer provided repeatable measurements with 0.075 degrees C resolution and standard deviation of 0.217 degrees C for homogeneous and layered tissue loads at temperatures between 32-45 degrees C. Within the 3.7-4.2 GHz band, EM noise rejection was good other than some interference from overhead fluorescent lights in the same room as the radiometer. The system response obtained for ideal water loads suggests that this digital radiometer should be useful for estimating subcutaneous tissue temperatures under a 6 mm waterbolus used during clinical hyperthermia treatments. The accuracy and stability data obtained in water test loads of several configurations support our expectation that single band radiometry should be sufficient for sub-surface temperature monitoring and power control of large multielement array superficial hyperthermia applicators.

Performance evaluation of a conformal thermal monitoring sheet sensor array for measurement of surface temperature distributions during superficial hyperthermia treatments.

PURPOSE: This paper presents a novel conformal thermal monitoring sheet (TMS) sensor array with differential thermal sensitivity for measuring temperature distributions over large surface areas. Performance of the sensor array is evaluated in terms of thermal accuracy, mechanical stability and conformity to contoured surfaces, probe self-heating under irradiation from microwave and ultrasound hyperthermia sources, and electromagnetic field perturbation. MATERIALS AND METHODS: A prototype with 4 x 4 array of fiber-optic sensors embedded between two flexible and thermally conducting polyimide films was developed as an alternative to the standard 1-2 mm diameter plastic catheter-based probes used in clinical hyperthermia. Computed tomography images and bending tests were performed to evaluate the conformability and mechanical stability respectively. Irradiation and thermal barrier tests were conducted and thermal response of the prototype was compared with round cross-sectional clinical probes. RESULTS: Bending and conformity tests demonstrated higher flexibility, dimensional stability and close conformity to human torso. Minimal perturbation of microwave fields and low probe self-heating was observed when irradiated with 915 MHz microwave and 3.4 MHz ultrasound sources. The transient and steady state thermal responses of the TMS array were superior compared to the clinical probes. CONCLUSIONS: A conformal TMS sensor array with improved thermal sensitivity and dimensional stability was investigated for real-time skin temperature monitoring. This fixed-geometry, body-conforming array of thermal sensors allows fast and accurate characterization of two-dimensional temperature distributions over large surface areas. The prototype TMS demonstrates significant advantages over clinical probes for characterizing skin temperature distributions during hyperthermia treatments of superficial tissue disease.

Multilayer conformal applicator for microwave heating and brachytherapy treatment of superficial tissue disease.

PURPOSE: The purpose of this study was to construct and perform preliminary functionality evaluations of a multilayer conformal applicator with provisions for thermal monitoring, tight conformity and simultaneous microwave heating and brachytherapy treatment of large-area contoured surfaces. MATERIALS AND METHODS: The multilayer conformal applicator consists of thermal monitoring catheters for fibre-optic monitoring of skin temperatures, a waterbolus, a PCB microwave antenna array, a dielectric spacer for brachytherapy considerations, brachytherapy catheters for delivering HDR radiation and an inflatable air bladder for improving conformity to contoured surfaces. The applicator also includes an elastic attachment structure to hold the applicator securely in place on the patient. The conformity of the applicator to irregular surfaces was evaluated through CT imaging of the applicator fitted onto a life-sized human torso phantom. The fluid flow dynamics of the waterbolus, which impact the effectiveness of temperature control, were evaluated with thermometry during a 19 degrees C step change temperature of the circulating water. RESULTS: CT imaging showed improved conformity to the torso phantom surface following the application of gentle inward pressure from inflating the outer air bladder. Only a small number of 1-5 mm sized air gaps separated the conformal applicator and tissue surface. Thermometry testing of the bolus fluid flow dynamics demonstrated temperature uniformity within +/-0.82 degrees C across a 19 x 34 x 0.6 cm area bolus and +/-0.85 degrees C across a large 42 x 32 x 0.6 cm area bolus. CONCLUSION: CT scans of the applicator confirmed that the applicator conforms well to complex body contours and should maintain good conformity and positional stability even when worn on a mobile patient. Thermometry testing of two different waterbolus geometries demonstrated that uniform circulation and temperature control can be maintained throughout large, complex bolus shapes.

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.

Combination applicator for simultaneous heat and radiation.

We present the development of operator and patient friendly conformal applicators that can deliver moderate temperature hyperthermia simultaneously with radiation in superficial tissue overlying contoured anatomy. This applicator combines the uniform heating capabilities of large area conformal microwave array (CMA) flexible printed circuit board applicators with a patient interface (coupling bolus) that facilitates positioning of brachytherapy sources at a fixed distance (e.g. 1.5 cm) from the skin. A customized inverse treatment planning program (IPSA) was used to optimize spacing of a parallel array of source catheters and separation distance from skin, and to characterize the effects of bolus thickness and conformal array curvature on radiation dose uniformity. Performance of a 15 cmx15 cm combination applicator was evaluated in flat and contoured homogenous muscle tissue models. Results demonstrate effective heating and radiation distributions to 1-1.5 cm depth and out to the periphery of the array. This applicator should prove useful for treatment of diffuse chestwall disease located over contoured anatomy that is difficult to treat with external beam radiation. By applying heat and radiation simultaneously for maximum synergism of modalities, this device should expand the number of patients that can benefit from effective thermoradiotherapy for superficial disease.

Design of spiral antennas for radiometric temperature measurement.

We are developing a microwave hyperthermia system for the treatment of chestwall recurrence of breast cancer. To improve power control of heating applicators, we intend to measure tumor temperature noninvasively during treatment, using radiometry. We are designing single-arm Archimedean spirals for use as receive antennas with a radiometer collecting thermal radiation from different tissue volumes at 1.9-2.3 and 3.7-4.2 GHz. We modeled the antennas numerically. First, we studied the antennas in terms of impedance matching to feedlines. Second, we investigated radiation mechanisms of the spirals radiating into lossy tissue. For small spacing between turns, the surface currents on the spiral were in phase on several neighboring windings, producing strong radiation from a circular, wavelength related region. At these locations, surface currents were also in phase on opposite sides of spiral, contributing to a more centrally peaked radiation pattern with deeper energy penetration than is obtained with a widely dispersed pattern. Finally, we studied the effect of distance from the spiral feedpoint to the radiating region on antenna efficiency. We found this distance should be minimized to reduce power loss from the less useful inner turns of the spirals. The optimization of these design parameters may produce significant improvement of antenna efficiency and improve depth-sensing capability of microwave radiometry.

Construction of a conformal water bolus vest applicator for hyperthermia treatment of superficial skin cancer.

Large area chestwall recurrence of breast carcinoma can be treated with moderate temperature hyperthermia in combination with radiation or chemotherapy. For diffuse chestwall disease, hyperthermia is best delivered with a conformal microwave array (CMA) applicator using a temperature-controlled water bolus designed specifically to fit complex contours and maintain contact with the tissue surface to prevent air gaps which distort the microwave power deposition pattern. In order to maintain the desired temperature range of 41-45 degrees C during local hyperthermia treatments, it is necessary to have an effective fluid flow system to serve as a buffer and prevent overheating of skin, which can lead to small blisters or, in rare cases, deeper burns. The fluid flow dynamics of a vest shaped open water bag design is evaluated with thermometry during a step temperature change of circulating water. The data confirm the feasibility of uniform circulation and temperature control throughout complex bolus shapes. This water bolus design should improve temperature uniformity of current treatments for superficial tissue disease.

Phantom and animal tissues for modelling the electrical properties of human liver.

The dielectric properties of human liver were characterized over the frequency range of 0.3-3 GHz for freshly excised tissue samples of primary hepatocellular carcinoma, metastatic colorectal carcinoma, and normal liver tissues resected from the tumour margin. On average, the dielectric constant (epsilon(r)) of freshly excised human liver tumour was 12% higher than that of surrounding normal liver, and the electrical conductivity (sigma) of tumour was 24% higher. In order to establish suitable tissue models for human liver, the electrical properties were compared to measurements of homogenous phantom mixtures, in vitro bovine liver, and in vivo canine and porcine liver tissues. The data demonstrate that there are several animal tissues that can be used to model the average dielectric properties of human liver reasonably accurately, and use of the most readily available bovine liver appears well-justified, even when stored for up to 10 days in a refrigerator. Additionally, the dielectric properties of in vitro liver remained stable over a large temperature range, with sigma rising only 1.1%/ degrees C in porcine liver (15-37 degrees C) and 2.0%/ degrees C in bovine liver (10-90 degrees C), and epsilon(r) decreasing < or =0.2%/ degrees C in both tissues. This effort identifies homogeneous solid and liquid phantom models and several heterogeneous in vitro tissues that adequately model the dielectric properties of human liver tumours for use in quantitative studies of microwave power deposition in liver.

SAR pattern perturbations from resonance effects in water bolus layers used with superficial microwave hyperthermia applicators.

This study examines the effect of various thickness water bolus coupling layers on the SAR (Specific Absorption Rate) patterns from Dual Concentric Conductor (DCC) based Conformal Microwave Array (CMA) superficial hyperthermia applicators. Previous theory has suggested that water bolus coupling layers can be considered as a dielectric resonator; therefore, it is possible for the impinging electric field to stimulate volume oscillations and surface wave oscillations inside the water bolus. These spurious oscillations will destructively or constructively interact with the impinging electric field to cause a perturbation of the applicator SAR pattern. An experiment was designed which consisted of mapping the electric field produced by a four element DCC CMA applicator in liquid muscle phantom at depths of 5 and 10mm in front of four different thickness water boli; 0 (no bolus) 4, 9 and 13mm. Using the Finite Difference Time Domain (FDTD) method, SAR distributions were calculated for similar test cases. It was found that for water bolus thicknesses of 9mm or greater, there is a marked perturbation of both experimental and theoretical SAR distributions. It is believed that this perturbation is experimental confirmation of the volume and surface wave oscillation theory described by previous investigators.

Non-invasive temperature profile estimation in a lossy medium based on multi-band radiometric signals sensed by a microwave dual-purpose body-contacting antenna.

Microwave radiometry has during the past two decades been investigated as a non-invasive scheme for measurement of subcutaneous tissue temperatures, basically for monitoring and control in hyperthermic treatment of cancer. In this effort, we test a contact-type, dual-purpose antenna with integral water bolus. To overcome conflicting optimization criteria in the integration of this thermometry technique with heat applicators exhibiting a large effective field size during superficial hyperthermia, a stacked configuration design is proposed, where the radiometer receive antenna (Archimedean spiral) is located on the front (skin) surface of the water bolus and the heating antenna (Dual-Concentric Conductor aperture) is placed on the bolus back surface. The motivation is to achieve homogeneous tissue heating simultaneously with non-invasive thermography of the target tissue under the applicator. This paper addresses the feasibility of predicting one-dimensional depth temperature profiles from multi-band brightness temperatures. The performance is investigated statistically by a Monte Carlo technique on both simulated and real heated-phantom data using up to six radiometric bands. Analysis of measured data shows that during the transient heating period in a solid lossy phantom, the inversion technique exhibits a precision (2sigmaT) and skewness (bias) of estimated compared to actual temperature profiles of better than +/-0.38 degrees C and +/-0.55 degrees C, respectively.