Theoretical comparison of the SAR distributions from arrays of modified current sheet applicators with that of lucite cone applicators using Gaussian beam modelling.

The technical comparison of Current Sheet Applicator (CSA) and Lucite Cone Applicator (LCA) arrays covering an area of approximately 20 x 20 cm2 is investigated based on Gaussian beam (GB) predicted SAR distributions. The comparison is made in muscle equivalent tissue at 1 cm depth (maximum SAR normalized to 100%) and over a volume of 3 cm depth under the aperture of the antennae. The planar SAR distribution is tested on field sizes (FSx: area covering x% SAR), penetration depth (PD) and homogeneity coefficient (HC = FS75/FS25). From the SAR volume, a SAR-Volume histogram (volume enclosing y% SAR/total volume) is calculated as well as the volumetric HC. First, the prototype CSA (aperture 58 x 67 mm2, FS50 = 21 cm2) is technically modified to assure clinical safety and load independence. The modified CSA, the D-CSA, has an aperture of 66 x 75 mm2 with an FS50 = 28 cm2 and a PD of 10 mm, the LCA (aperture 105 x 105 mm2) has an FS50 = 76 cm2 and PD = 12 mm. The HC equals 0.21 (D-CSA), respectively 0.22 (LCA). Secondly, a 3 x 3 D-CSA array is compared with a 2 x 2 LCA array. The FS50s equals 72% (D-CSA), respectively 75% (LCA). The SAR-volume histograms, planar and volumetric HC show no significant difference; however, the planar HCs for D-CSA and LCA increase from 0.2-0.3, indicating that incoherently powered arrays from these antennae build SAR distributions constructively.

A ferrite core/metallic sheath thermoseed for interstitial thermal therapies.

An alternative form of ferromagnetic seed for thermal therapy has been developed following Matsuki, Murakami, and their colleagues [1]-[4]. A nearly lossless ceramic ferrite core (FC) is surrounded by an electrically conductive sheath. The FC has a high relative intrinsic permeability, typically 3000 at low magnetic field strengths, and a sharp transition from the ferrimagnetic state to the nonmagnetic state. The sheath is either a metallic tube or coating on the core. When this composite seed is excited with a radiofrequency magnetic field, large eddy currents are induced in the metallic sheath (MS) due to the concentrated magnetic flux in the core leading to Joule heating. Advantages of this configuration are that this ferrite core/metallic sheath (FC/MS) thermoseed has high power absorption efficiency and a sharp transition compared to ferromagnetic alloy systems; means of optimizing efficiency are apparent from simple expressions; the outer sheath can be of any biocompatible metal; the production method for the ferrites leads to large quantities of seeds with reproducible properties. The FC/MS configuration solves many of the technical problems that have hindered the clinical implementation of thermally regulating ferromagnetic implants for thermal therapies.

Power absorption and temperature control of multi-filament palladium-nickel thermoseeds for interstitial hyperthermia.

In interstitial hyperthermia using ferromagnetic seeds, multi-filament seeds have gained interest because of a more effective power absorption than solid seeds. Palladium-nickel (PdNi) seeds composed of filaments with diameters in the range from 0.1 to 1.0 mm (maximally 90 filaments) have been investigated to find the conditions for optimal power absorption and temperature control. Magnetic and calorimetric experiments have shown that a decreasing filament radius results in a more effective power absorption. The power absorption approaches a common asymptote for high field intensities at all filament diameters. This asymptotic behaviour can be understood as a consequence of the approach of saturation magnetization of PdNi. The sharpness of the transition at the Curie temperature, which is a measure for the quality of temperature control, improves as the magnetic field strength increases, but it is limited by the asymptote of the power absorption. When the asymptote has been reached the quality of temperature regulation of a seed can only be improved by increasing the amount of PdNi, e.g. by increasing the number of filaments. Calculations of the power absorption, using the generally applied theory based on a linear relation between the magnetization of PdNi and the magnetic field strength, do not correspond quantitatively with experimental results for seeds having an induction number smaller than the 'optimal value' of 2.5. For these seeds the measured heat production is larger than the calculated one.

Miniature dipole E-field probes for characterizing both phase and amplitude of microwave radiators for hyperthermia.

This paper describes a system for characterizing th electric field patterns of microwave radiators in lossy media, in particular, of those used in hyperthermia treatments for cancer therapy. We discuss the design, fabrication and testing of small, minimally-perturbing electric field probes which are capable of measuring both amplitude and phase. An appropriate test configuration for mapping field patterns radiating from hyperthermia applicators (antennae) also is described. The system was developed specifically for the evaluation of applicators centered at 434 MHz and 915 MHz.

Clinical hyperthermia with a new device: the current sheet applicator.

PURPOSE: The current sheet applicator (CSA) is a newly developed microwave hyperthermia device. Advantages over commercial microwave applicators include its small size and high ratio of heating area to physical aperture area. These physical characteristics make the CSA excellent for heating constricted areas and allow the use of arrays of CSAs over large surfaces. This study examines the clinical efficacy of the CSA for heating superficial malignant tumors. METHODS AND MATERIALS: From December 1989 through October 1991, 19 patients with recurrent or metastatic superficial malignant tumors were treated once or twice weekly to 30 hyperthermia fields using one to four CSAs. Each field received from one to four hyperthermia treatments for a total of 74 treatments. The treatment objective was to elevate the tumor temperature to a minimum of 42.5 degrees C for 30 min (2 patients) or 60 min (17 patients). Intratumor temperatures were measured with percutaneous fiberoptic thermometry probes. All patients received concurrent fractionated radiation therapy with total dose ranging from 20 to 65 Gy (median 46 Gy). Seventeen of the 30 fields had been previously irradiated to a median dose of 50 Gy. RESULTS: Mean values for the maximum temperature, average temperature, and minimum temperature were 43.6 degrees C +/- 1.0, 42.2 degrees C +/- 1.4, and 41.0 degrees C +/- 1.5, respectively. Mean values for T50 and T90 were 42.2 degrees C +/- 1.1 and 41.0 degrees C +/- 1.3, respectively. The overall response rate for all assessable fields was 96%. Only Only three responding tumors have progressed with a median follow-up period of 6 months. Treatment related morbidity was generally mild and self-limited. CONCLUSION: The CSA is a promising new microwave hyperthermia device capable of heating superficial tumors to therapeutic temperatures. When used in combination with radiotherapy, response rates are excellent without excessive toxicity.

Fast and efficient computer modeling of ferromagnetic seed arrays of arbitrary orientation for hyperthermia treatment planning.

PURPOSE: Effective hyperthermia treatment planning requires an ability to predict temperatures quickly and accurately from an arbitrary distribution of power. Our purpose was to design such a fast executing computer code, MGARRAY, to compute steady-state temperatures from ferromagnetic seed heating, allowing seeds to have arbitrary orientations and to be curved to permit more realistic modeling of clinical situations. We further required flexibility for the tissue domain, allowing inhomogeneity with respect to thermal conductivity and blood perfusion, as well as an arbitrary shaped boundary. METHODS AND MATERIALS: MGARRAY uses multigrid methods and a finite volume discretization to solve the Pennes bioheat transfer equation in three dimensions. We used MGARRAY to compare temperature distributions that result from an array of straight, parallel seeds and from an array of seeds that were curved and tilted randomly by 13 degrees. RESULTS: On a personal workstation the Central Processing Unit (CPU) time of MGARRAY was under 4 min. We found that the median temperature in a predetermined target volume was approximately 0.8 degrees C higher in the straight array than in the curved array. At specific locations within the target volume temperature differed by approximately 0.5-0.9 degrees C, but could differ by up to several degrees, depending on proximity to a seed and the level of blood perfusion. CONCLUSION: These differences can impact on retrospective analyses whereby temperatures at a few locations are used to infer the overall temperature field and blood perfusion levels. The flexibility and computational speed of MGARRAY could potentially lead to a substantial improvement in both retrospective and prospective hyperthermia treatment planning.

A phase I study of the toxicity of regional hyperthermia with systemic warming.

This study examines the consequences of allowing moderate systemic hyperthermia during regional heating of the abdomen and pelvis in 29 patients participating in Phase I studies of hyperthermia combined with chemotherapy or radiation therapy. In Group 1 (20 patients, 42 treatments), systemic temperatures were limited by employing surface cooling, while in Group 2 (9 patients, 24 treatments), surface warming and insulation were used so that systemic temperature would rise. Mean time-averaged oral temperatures were 38.4 degrees C and 39.9 degrees C for Groups 1 and 2, respectively. Time-averaged mean regional temperatures were 40.2 +/- 0.7 degrees C and 41.5 +/- 0.2 degrees C for Groups 1 and 2, respectively (p < .001). Regional temperatures > or = 41.0 degrees C were achieved by 64% of Group 1 and all Group 2 patients. The mean time-averaged power required was significantly lower for Group 2 (453 W vs 740 W; p = .032), as was the incidence of pain. Mean maximum pulse rate was significantly higher in Group 2, although this was not associated with symptoms. Allowing systemic temperature to rise decreased power requirements and treatment-related pain, at the cost of an asymptomatic increase in heart rate. The results suggest that regional heating may be more readily achieved in the setting of elevated systemic temperature.

Temperature distribution in tissues from a regular array of hot source implants: an analytical approximation.

An approximate analytical model based upon the bioheat transfer equation is derived and used to calculate temperatures within a perfused region implanted regularly with dielectrically coated hot source implants; for example, hot water tubes, electrically heated rods, or inductively heated ferromagnetic implants. The effect of a regular array of mutually parallel heat sources of cylindrical shape is approximated by idealizing one of the boundary conditions. The solution, as could be expected, is in terms of modified Bessel functions. In calculating the temperature of each thermoregulating source in the array, the steady state power balance is enforced. The important feature of the model is that the finite size of implant diameter and its dielectric coating can be incorporated. The effect of thickness and thermal conductivity of the coating on the source and tissue temperatures along with various other interesting features are deduced from this model. The analytically calculated implant and tissue temperatures are compared with those of a numerical 3-D finite difference model. The analytical model also is used to define a range of parameters such that minimal therapeutic temperatures will be achieved in the implanted volume without exceeding prescribed maximum temperatures. This approach leads to a simple means of selecting implant spacing and regulation temperatures of hot source methods prospectively.

Three-dimensional simulations of ferromagnetic implant hyperthermia.

A general three-dimensional planning program has been developed for hyperthermia treatments for cancer. In this study, the program is used to analyze the three-dimensional temperature distributions generated by interstitial ferromagnetic implants. An empirical power absorption formula developed by Haider for thermally self-regulating nickel-silicon ferromagnetic seeds has been used to calculate the seed power absorption as a function of seed temperature. By properly choosing the seed type (Curie point of seeds), and by using appropriate seed spacing, this heating modality can generate desirable three-dimensional temperature distributions for many different situations over a fairly large range of blood perfusion values. Detailed information regarding the choice of the Curie points of the seeds and the seed spacing for certain blood perfusions is also given as a quantitative guide for treatment planning.

Current sheet applicator arrays for superficial hyperthermia of chestwall lesions.

The current sheet applicator is an electromagnetic heating device whose size may be chosen virtually independent of frequency even though practical limitations may restrict it to VHF and UHF bands. In this paper we investigate absorbed power distributions in muscle tissue from current sheet applicators when used as elements of a planar array intended for superficial hyperthermic treatment of tumours. Advantages offered by current sheet applicators for tissue heating include compact size, a linear polarization of the induced electric field and relatively large heating area. It is shown that the effective field produced by a pair of these elements is continuous regardless of whether the common edges of the elements are perpendicular or parallel to the direction of impressed current. The feasibility of customizing the shape and size of the field is also illustrated. The absorbed power distribution patterns due to a coherently driven array operating around 434 MHz is relatively insensitive to phase variations of about 20 degrees but is sensitive to relative power level variations as low as 10%. Mutual coupling between array elements may be reduced to acceptable levels by incorporating suitable spacing between them. It is also demonstrated that there is good agreement between measurements of absorbed power distributions and predictions using the Gaussian beam model.

Errors in the two-dimensional simulation of ferromagnetic implant hyperthermia.

An empirical power absorption formula developed by Haider et al. (1991) for thermally self-regulating nickel-silicon ferromagnetic seeds has been incorporated into a three-dimensional patient treatment planning programme to calculate the seed power absorption as a function of seed temperature. The programme has been used to evaluate systematically the accuracy of two- versus three-dimensional simulations for ferromagnetic implant hyperthermia. The results show that two-dimensional simulations can significantly overestimate temperatures. Consequently, three-dimensional simulations are necessary for accurate hyperthermia treatment planning.

Heating pattern of helical microwave intracavitary oesophageal applicator.

Helical microwave intracavitary oesophageal (HMIO) applicators were designed to operate at frequencies of 433 MHz and 915 MHz. Heating patterns were studied within muscle-equivalent phantom by thermographic camera and fibreoptic thermometers. The results showed that frequency significantly influenced the microwave heating pattern. The 433 MHz applicator had a single power deposition region, the longitudinal specific absorption rate (SAR) distribution appeared to be nearly even, and the maximum SAR value occurred close to the centre of the active length of the applicator. The 915 MHz applicator had two power deposition regions, the peak SAR values occurred at about 1/4 and 3/4 of the active length respectively. The radial SAR distribution suggested that there is no obvious difference between the 433 MHz and 915 MHz applicators in that the average radial penetration of 50% surface SAR (RP50) was about 0.65 cm. It was also shown that power deposition was axially symmetric for both 433 MHz and 915 MHz HMIO applicators. It is shown that better impedance matching is more important for intracavitary hyperthermia than for external hyperthermia. Choosing HMIO applicators in clinical practice is also discussed.

Interstitial thermoradiotherapy of brain tumors: preliminary results of a phase I clinical trial.

A Phase I clinical trial has been initiated to determine the feasibility, tolerance, and toxicity of interstitial thermoradiotherapy in the treatment of high-grade supratentorial brain gliomas. Hyperthermia was delivered by means of thermally-regulating ferromagnetic implants afterloaded into stereotactically placed plastic catheters. Heat treatments were given immediately before interstitial irradiation; in addition, five patients received a second heat treatment at the completion of brachytherapy. The desired target temperature for the 60-minute hyperthermia session was between 42 degrees C and 45 degrees C. Following hyperthermia, the catheters were afterloaded with Ir-192, which delivered a variable radiation dose of 14-50 Gy depending on the clinical situation. Interstitial irradiation was supplemented with external beam radiotherapy (40-41.4 Gy) in patients with previously untreated tumors. A total of 14 patients (4 males, 10 females) have been treated to date on this protocol. Eleven of the patients had a diagnosis of glioblastoma multiforme, whereas three had anaplastic astrocytoma. The mean implant volume was 61.5 cm3 (range: 9-119 cm3); the median number of interstitial treatment catheters implanted was 19 (range: 7-33). Continuous temperature monitoring was performed by means of multisensor thermocouple probes inserted in the center as well as in the periphery of the tumor. Of the 175 monitored intratumoral points, 83 (47%) had time-averaged mean temperatures of greater than 42 degrees C, and only 12 sensors (7%) exceeded a temperature of 45 degrees C. Among the 19 heat treatments attempted, there have been four minor acute toxicities, all of which resolved with conservative medical management and one major complication resulting in the demise of a patient. These preliminary results indicate that ferromagnetic implants offer a promising new approach to treating brain tumors with hyperthermia.

Treatment planning of template-guided stereotaxic brain implants.

We have initiated a Phase I clinical trial of interstitial hyperthermia induced with inductively heated ferromagnetic implants in combination with Ir-192 implants for glioblastomas and anaplastic astrocytomas of the brain. For speed and accuracy of the implant procedure, and to control the radiation and thermal dose, a stereotaxic frame is used to position a template. We have modified the Brown-Roberts-Wells frame to be used with a variety of templates which we designed. On the morning of the implant procedure, a CT scan is done, and a CT-based treatment plan is then completed before the patient goes to the operating room. We also describe the CT-based treatment planning system developed to accommodate the template-guided implant and illustrate its clinical use.

Experimental assessment of phased-array heating of neck tumours.

An investigation of phased-array microwave systems (PAMS) for non-invasively inducing hyperthermia, primarily in neck lesions, has been done with implications for applications at other sites such as lung and pelvis. Our general approach was to combine numerical and analytical approaches with parallel experimental studies. In this paper we will concentrate only on the experimental aspects. The object, such as a homogeneous cylindrical phantom or a neck phantom, was encircled with several standard applicators driven by a single source, but with relative phase and amplitude control over each applicator. The relative phases of the applicators were adjusted by using an implanted monopole antenna connected to an HP network analyser. Power was applied and the specific absorption rate (SAR) was determined by using split phantoms and thermography or by measuring temperature transients dT/dt, recorded by implanted thermometer probes. We found that at 915 MHz for our applicators (SMA Co.) the centre of an 11 cm diameter muscle-like phantom heated to about 33% of the value at the surface in front of the applicator. Similarly, we were able to show significant SAR at the centre of realistically sized neck phantoms using four phased apertures of 915 MHz. Furthermore, substantial improvement was observed if the frequency was lowered to about 400 MHz.

Use of Gaussian beam model in predicting SAR distributions from current sheet applicators.

The Gaussian beam model is shown to be a good predictor of SAR distributions due to current sheet applicators (CSAs). It is fast, efficient and adaptable. SAR distributions from a single applicator and from simple arrays of CSAs in homogeneous and layered lossy media are computed at 434 and 450 MHz at CPU times of less than 60 s. The good agreement between theory and experiment justifies the use of the Gaussian beam model to predict SAR distributions from CSAs.

Interstitial thermoradiotherapy: thermal dosimetry and clinical results.

From August 1977 to August 1986, 72 patients with advanced primary or recurrent cancers were treated using interstitial thermoradiotherapy. Sites treated included the pelvis in 49 patients, the head and neck in 15, and other sites in six. Median tumor volume was 52 cm3, and all but nine patients had received prior irradiation. In 69 patients, hollow stainless steel catheters were implanted and used as electrodes with a 0.5 MHz radiofrequency (RF) generator, whereas in three patients, standard plastic Henschke tubes were used with a commercially available interstitial microwave (MW) system operating at 915 MHz. Most patients were heated intraoperatively for 30 minutes, aiming for a minimum measured intratumoral temperature (Tmin) of 42 degrees C. The implant was occasionally preceded by external irradiation, and after hyperthermia, the catheters were afterloaded with 192Ir for brachytherapy. Tmin exceeded 42 degrees, 42.5 degrees, 43 degrees, and 44 degrees in 25, 16, 12, and 3, respectively, of 70 patients with temperature data available, and the probability of successful heating was independent of tumor volume or site. Twenty-five of 69 (36%) evaluable patients achieved a complete response (CR). Probability of CR demonstrated a significant univariate dependence upon Tmin, radiation dose, site treated, and tumor volume, but multivariate analysis showed only three significant predictor variables: tumor volume, radiation dose, and Tmin. The probability of a CR ranged from 95% for patients with small tumors receiving high doses of radiation and adequate heat, to 5% for patients with large tumors receiving low radiation doses and less than adequate heat. Of 25 patients with CR, 10 relapsed; median response duration was less than 18 months, depended marginally upon disease site, and was independent of Tmin, radiation dose, and tumor volume. Seventeen patients sustained a complication, of which nine were severe enough to require hospitalization or surgery. All severe complications occurred in patients with pelvic tumors. The probability of a complication of any severity had a significant univariate association with maximum intratumoral temperature (Tmax) and tumor size. We conclude that interstitial thermoradiotherapy offers the promise of heating large tumors in locations where externally applied hyperthermia has not been successful.

Errors between two- and three-dimensional thermal model predictions of hyperthermia treatments.

A simulation program to study the three-dimensional temperature distributions produced by hyperthermia in anatomically realistic inhomogenous tissue models has been developed using the bioheat transfer equation. The anatomical data for the inhomogeneous tissues of the human body are entered on a digitizing tablet from serial computed tomography (CT) scans. Power deposition patterns from various heating modalities must be calculated independently. The program has been used to comparatively evaluate two- and three-dimensional simulations in a series of parametric calculations based on a simple inhomogeneous tissue model for uniform power deposition. The conclusions are that two-dimensional simulations always lead to significant errors at the ends of tumors (up to tens of degrees). However, they can give valid results for the central region of large tumors, but only with tumor blood perfusions greater than approximately 1 kg/m3/s. These conclusions from the geometrically simple model are substantiated by the results obtained using the full three-dimensional model for actual patient anatomical simulations. In summary, three-dimensional simulations will be necessary for accurate patient treatment planning. The effect of the thermal conductivity, used in the models, on the temperature field has also been studied. The results show that using any thermal conductivity value in the range of 0.4 to 0.6 W/m/degrees C sufficiently characterizes most soft tissues, especially in the presence of high blood perfusion. However, bone (thermal conductivity of 1.16 W/m/degrees C) and fat (thermal conductivity of 0.2 W/m/degrees C) do not fit this generalization and significant errors result if soft tissue values are used.