A Study of the Effect of Sensor Placement and Perfusion Pattern Variations on Thermal Tomography Solutions in Hyperthermia

The ability to predict complete temperature profiles from temperature measurements at a few locations is an important and difficult problem in cancer hyperthermia treatments; it is especially difficult because of a lack of knowledge of the tissue blood perfusion patterns and magnitudes. This paper describes an attempt to determine some of the characteristics of the problem so that it may be solved eventually. Results of simulation studies are presented for the solution of this combined state and parameter estimation problem using a steady-state technique previously developed. Particular attention is paid to the problems of estimating 1) the complete temperature field when the tissue perfusion pattern is unknown, and 2) the maximum and minimum tissue temperatures in situations where those temperatures have not been measured. The results indicate that this steady-state technique works well if the perfusion pattern is known, the pattern can be modeled accurately, and there is one temperature measurement for each unknown perfusion parameter. The applicability of the technique is seriously limited when any of these conditions are not met, since the predicted temperature field may then have significant errors.     

Direct computation of ultrasound phased-array driving signals froma specified temperature distribution for hyperthermia

This paper presents a new method which obtains ultrasound hyperthermia applicator phased-array element driving signals from a desired temperature distribution. The approach combines a technique which computes array element driving signals from focal point locations and intensities with a new technique which calculates focal point locations and power deposition values from temperature requirements. Temperature specifications appear here as upper and lower bounds within the tumor volume, and a focal point placement algorithm chooses focal patterns capable of achieving the temperature range objective. The linear algebraic structure of the method allows rapid calculation of both the phased-array driving signals and an approximate temperature field response. Computer simulations verify the method with a spherical section array (SSA) for a variety of temperature specifications and blood perfusion values. This scheme, which applies to any phased-array geometry, completes an essential step in both treatment planning and feedback for hyperthermia with ultrasound phased-array applicators.     

Gain optimization of a near-field focusing array for hyperthermiaapplications

A variation of the array gain optimization problem has arisen in the study of microwave arrays used for hyperthermia, the heating of biological tissue. For a given array configuration and arbitrary medium it is desired to maximize the power deposition at a prescribed focus in the near field of the array. The authors show how the optimum excitation can be found by solving an eigenvalue problem. Their optimum solution is compared with two other solutions, namely a closed-form solution which optimizes the power in one linear polarization of the radiated field, and a solution based on the popular conjugate-field scheme     

Feasibility of ultrasound hyperthermia with waveguide interstitialapplicator

Interstitial and intracavitary ultrasonic hyperthermia applicators facilitate well-controlled power deposition in tissues. In this paper, analysis of temperature elevation and experimental results in tissue phantom, animal tissue in vivo and animal tissue in vitro are presented for a waveguide applicator intended for treatment of brain tumors. It consisted of a G18 hypodermic needle attached via a conical velocity transformer to a 12.7-mm-diameter piezoelectric disk operated at 1.0 MHz. The axial acoustic pressure distribution had a standing-wave pattern with the four cycles/cm spatial periodicity. This periodicity was absent in the temperature distribution in tissue phantoms. The simulations based on a solution to the effective heat conductivity equation indicated that the hyperthermic range can be reached within a 4- and a 10-mm radius around the applicator for a 21- and a 60-mm sample diameters, respectively, with reasonable input power. The first number corresponded closely to the 5-mm radius observed in porcine brain in vivo and the second one came close to the 9-mm radius in porcine brain in vitro. The presented results demonstrate the potential of the ultrasound waveguide interstitial applicator for hyperthermia of small volume tumors     

Hyperthermia and Cancer Therapy: A Review of Biomedical Engineering Contributions and Challenges

In this paper, we attempt to give an overview of the status of hyperthermia as a modality for cancer treatment from an engineer's point of view. By hyperthermia we mean elevating the tumor tissue to the temperature range of 42-50°C and holding it at this temperature for 30 min-1 h. We give a brief history of the field, some comments on the biological rationale, and a survey of present methods for producing hyperthermia using electromagnetic and ultrasonic techniques. Finally, we give some comments on the success of present systems in achieving the specifications set by the clinicians and suggest some fundamental problems we feel need to be solved if hyperthermia is going to be able to make a contribution to the cure and control of this disease.     

Optimal power deposition with finite-sized, planar hyperthermiaapplicator arrays

Improved hyperthermia applicator technology is allowing finer spatial power resolution within the heated tissue volume. Effective utilization of these planar applicator arrays requires an understanding of the interrelationships between the lateral dimensions of the tumor and the applicators, the power field produced by the applicators, the amount of surface cooling, the tumor tissue blood perfusion, and the normal tissue blood perfusion. These interrelationships are investigated using three-dimensional power patterns and temperature fields produced by optimizing the power amplitudes of the individual applicators located within an array of small, but finite, planar applicators. Five major conclusions are obtained. First, optimization works and is effective in determining optimal power fields. Second, for optimal treatments the lateral dimensions of a single superficial applicator need to extend beyond the tumor boundary. Third, surface cooling is needed to reduce the high normal tissue temperatures at shallow depths. Fourth, finer power resolution becomes more important as the tumor size decreases, but, little improvement in the temperature field is achieved beyond a 3 x 3 array configuration. Fifth, increasing the normal blood perfusion rate can decrease the temperature on the tumor boundary if direct power deposition on that boundary is unavailable.     

Three-dimensional electromagnetic power deposition in tumors usinginterstitial antenna arrays

Interstitial arrays of insulated antennas have shown promise for microwave hyperthermia treatment of deep-seated tumors. Available analytical techniques for predicting the electromagnetic (EM) power deposition of these antennas have been limited to the case of a homogeneous conductive medium surrounding the array. Since tumors and host tissue may differ in their electrical characteristics, it is necessary to consider the impact of this variation in electrical properties and the geometry of the tumor in the calculation of the EM field distribution and power deposition pattern when modeling interstitial antennas. In this paper a three-dimensional model of a tumor of arbitrary shape subjected to the fields of an interstitial antenna array is developed to predict the EM power deposition in an inhomogeneous tumor-tissue medium. The volume integral equation for the imbedded tumor is developed and solved by method of moments. The incident fields are calculated based on the available formulation of interstitial antennas in homogeneous media. The accuracy of the developed computer code was checked by comparing the results from the volume integral approach with the Mie solution for the special case of spherical tumors. Good comparison was obtained for tumors with properties approximately 25 percent different from those of the surrounding tissue. Comparisons of results from models of antenna arrays with and without imbedded tumors show significant differences in their predictions of the EM power deposition in the tumor. Hyperthermia protocols generally specify uniform temperature distribution within the tumor. The developed inhomogeneous model was used to examine the feasibility of controlling the uniformity of the power deposition pattern in large tumors by adjusting the amplitude or relative phase between the array elements. Results are presented to show that a phase lead of +90 degrees or relative amplitude of 4.0 on one antenna in a square array of four antennas could be used to shift the power deposition pattern to sequentially heat outer portions of a 2 cm diameter tumor, thereby achieving a more uniform time-averaged temperature distribution in the tumor.     

Theoretical basis for controlling minimal tumor temperature duringinterstitial conductive heat therapy

This paper describes simulation of steady-state intratumoral temperatures achieved by a simple modality of local heat therapy: interstitial treatment with parallel arrays of warmed, conductive heating elements. During "conductive heating" power is directly deposited only in the interstitial probes. Adjacent tissue is warmed by heat conduction. Simulations of interstitial conductive heating involved solution of the bioheat transfer equation on a digital computer using a finite difference model of the treated tissue. The simulations suggest that when the complete temperature distributions for conductive interstitial hyperthermia are examined in detail, substantial uniformity of the temperature distributions is evident. Except for a thin sleeve of tissue surrounding each heating element, a broad, flat central valley of temperature elevation is achieved, with a well defined minimum temperature, very close to modal and median tissue temperatures. Because probes are inserted directly in tumor tissue, the thin sleeve of overheated tissue would not be expected to cause normal tissue complications. The temperature of the heated probes must be continuously controlled and increased in the face of increased blood flow in order to maintain minimum tumor temperature. However, correction for changes in blood flow is possible by adjusting probe temperature according to a feedback control scheme, in which power dissipation from each probe is the sensed input variable. Conductive interstitial heating with continually controlled probe temperature deserves investigation as a technique for local hyperthermia therapy.     

Automatic temperature controller for multielement array hyperthermia systems

This paper concerns the optimization and performance analysis of an automatic control algorithm for managing power output of large multielement array hyperthermia applicators. Simulation and corresponding measurement of controller performance in a solid tissue equivalent phantom model is utilized for analysis of controller response to dynamically varying thermal load conditions that simulate clinical treatments. The analysis leads to an optimum controller which demonstrates the ability to achieve a uniform and stable temperature profile over a large surface area regardless of surrounding thermal load. This paper presents several advancements to the performance of a previously published control routine, including: 1) simplified simulation techniques for thorough characterization of controller performance; 2) an optimization procedure leading to an improved hybrid control algorithm for maintaining optimal performance during periods of both "rising" and "steady-state" temperature; 3) performance analysis of a control algorithm tailored for large area hyperthermia treatments with a mulitelement array applicator. The optimized hybrid controller is applied to the conformal microwave array (CMA) hyperthermia system previously developed for heating large area surface disease such as diffuse chestwall recurrence of breast carcinoma, and shown to produce stable, uniform temperatures under the multielement array applicator for all thermal load conditions.     

Energy deposition in simulated human operators of 800-MHz portable transmitters

The measured values of energy deposited in simulated human tissue exposed for one minute in the immediate vicinity of 800 MHz portable radio transmitters are presented. The deposited RF energy was evaluated by temperature measurements. The portable radio used in the tests had a 6-W experimental transmitter operating at 840 MHz. Two different antennas were tested for energy deposition: a sleeve dipole and a resonant whip. The two antennas have given substantially different results indicating different field structures near the two radiators. The experiments with flat slabs have shown that the sleeve dipole deposits higher levels of power density than the resonant whip in the near field although the length of the latter radiator is about half the size of the former. The temperature profiles generated by both antennas inside the head of the simulated operator indicate the presence of a "hot spot" about 1 in below the surface of the temporal bone. This phenomenon was not detected previously at lower frequencies. The short antenna exposes the eye of the operator to more intense power deposition than the sleeve dipole. The temperature increases measured during the investigation are so small that no thermal damage to tissue should be caused by normal use of the portable radio.     

Impedence method for calculation of power deposition patterns in magnetically induced hyperthermia

To obtain a detailed view of the power deposition pattern resulting from time-varying magnetic fields used in hyperthermia, we have developed a method of modeling portions of the human body using an impedance network. The region of interest is subdivided into a number of cells, each of which is then replaced by an equivalent impedance, and the currents induced in the resulting network due to the prescribed magnetic field are found by the application of circuit theory.     

Inference of Complete Tissue Temperature Fields from a Few Measured Temperatures: An Unconstrained Optimization Method

In clinical applications of hyperthermia, tissue temperature measurements are made at only a few selected locations because of patient tolerance and practical clinical limitations. Since it is necessary to know the complete tumor temperature field in order to effectively evaluate a treatment, methods of interpolating and extrapolating must be developed to estimate the unmeasured tumor temperatures. The difficulty of making such estimates from only a few data points is compounded by a lack of knowledge of the tumor blood perfusion characteristics. To solve this problem we have developed an iterative state and parameter estimation algorithm to attempt to estimate complete tissue temperature fields from temperatures measured at selected locations when tissue perfusion values are unknown. This approach uses either a conjugate gradient or a relaxation method to minimize the difference between the measured temperatures and the temperatures predicted at those same locations by the bioheat transfer equation. To investigate the mathematical capabilities and limitations of this technique a sensitivity analysis has been performed by applying it to a large number of simulated one-dimensional hyperthermia treatments. To illustrate its applicability to clinical situations, the estimation algorithm is also applied to temperature measurements from an animal experiment. The simulation results show that the technique is promising for estimating the complete tumor temperature distribution from measurements at a small number of sampled locations, if some knowledge of the blood perfusion pattern is available.     

多层媒质中声聚焦控制及其用于热疗的分析

基于伪逆算法提出了一种可对多层生物组织中的肿瘤进行声聚焦控制的方法.对一10×10个正方形阵元的相控阵在肿瘤位于不同深度处时产生的声场进行了仿真,同时计算了生物组织内不同时刻的温度分布,并对不同声辐射功率下加热到相同热剂量时的温度分布进行比较.研究结果表明,该方法能快速有效地对不同深度不同尺寸的肿瘤进行准确地声能聚焦控制;声辐射功率越大时,治疗区域中相同等温曲线所围区域较窄;激发频率、声辐射功率及照射时间均相同时,肿瘤在深度较浅位置时治疗区域温度要高,且此区域较粗短,而在较深位置时治疗区域温度相对较低,且此区域变得狭长.     

Body conformable 915 MHz microstrip array applicators for largesurface area hyperthermia

The optimal treatment with hyperthermia of superficially located tumors which involve large surface areas requires applicators which can physically conform to body contours, and locally alter their power deposition patterns to adjust for nonuniform temperature caused by tissue inhomogeneities and blood flow variations. A series of 915 MHz microstrip array applicators satisfying these criteria have been developed and clinically tested. Clinical and engineering design tradeoffs for practical devices are discussed. Measurements taken in tissue equivalent phantoms and a summary of our clinical experiences with these microstrip arrays are presented.     

EMI-immune thermocouple thermometry in RF hyperthermia systems

The authors outline the advantages of using thermocouple thermometry for temperature monitoring during localized electromagnetic hyperthermia. Problems faced in used metallic probes during RF power delivery are discussed from both theoretical and practical points of view. Solutions to electromagnetic interference (EMI) problems are suggested, and the actual implementation of an EMI-immune thermometric system suitable for temperature monitoring in RF hyperthermia is described     

A Review of Magnetic Induction Methods for Hyperthermia Treatment of Cancer

Magnetic induction methods of producing power absorption in tissue are used for achieving tumor hyperthermia in experimental cancer therapy. Electromagnetic field distributions and associated tissue energy absorption rates (SAR) of concentric, pancake, and coaxially paired current coils are discussed. Application of the bioheat transfer equation using these SAR distributions yields predictions of normal tissue and intratumoral temperature elevations. The corroboration of these predictions by phantom, animal, and human studies confirms the importance of bioheat transfer modeling in evaluation of these hyperthermia methods. Tumor sizes, depths, and locations likely to be therapeutically heated by magnetic induction techniques are reviewed, based upon available evidence.     

Heating patterns generated by phase modulation of a hexagonal arrayof interstitial antennas

In this paper, we investigate an array of six interstitial microwave antennas used for hyperthermia cancer treatment. The purpose is to generate both uniform and controlled nonuniform heating patterns in biological tissue by phase modulating the signals applied to each antenna. The array consists of six antennas positioned on the corners of a hexagon. The distance between two diagonal antennas is 4 cm. The distributions of absorbed power per unit mass within the array are computed, and then converted into temperature distributions through a thermal conduction simulation. The SAR and temperature patterns are presented in both the lateral plane (perpendicular to the antennas) and the axial plane (parallel with the antennas). By proper phase modulation of microwave signals applied to each antenna, a uniform heating pattern can be produced within the entire array volume. Also, a peripheral heating pattern may be generated around the array; again, by using the proper phase modulation. The modulation schemes for generating both types of heating patterns are discussed.     

Microwave hyperthermia induced by a phased interstitial antennaarray

An interstitial microwave antenna array for hyperthermia cancer treatment is investigated. The purpose is to generate both uniform and controlled nonuniform temperature distributions in biological tissue by modulating the phases of the signals applied to each antenna. The array has four antennas positioned on the corners of a 2 cm square. The distributions of absorbed power within the arrays are computed and then converted into temperature distributions through a heat conduction simulation. The temperature patterns over phantom muscle are presented in both the lateral plane (perpendicular to the antennas) and the axial plane (parallel to the antennas). It is found that by proper phase modulation of radiofrequency signals applied to each antenna, a uniform heating can be produced in the entire array volume     

Combined Hyperthermia and Photodynamic Therapy Using a Sub-THz Gyrotron as a Radiation Source

In this paper, we present results of a hyperthermia treatment of malignant tumors using a gyrotron as a radiation source for heating of the cancerous tissue. They clearly demonstrate the efficiency of the irradiation by sub-THz waves, which leads to steady decrease of the volume of the tumor and finally to its disappearance. A combination of hyperthermia and photodynamic therapy (PDT) that utilizes a novel multifunctional photosensitizer has also been explored. In the latter case, the results are even more convincing and promising. In particular, while after a hyperthermia treatment sometimes a regrowth of the tumor is being observed, in the case of combined hyperthermia and PDT such regrowth has never been noticed. Another combined therapy is based on a preheating of the tumor by gyrotron radiation to temperatures lower than the hyperthermia temperature of 43 °C and followed then by PDT. The results show that such combination significantly increases the efficiency of the treatment. We consider this phenomenon as a synergy effect since it is absent when hyperthermia and PDT are applied separately, and manifests itself only when both methods are combined.     

Optimization of the deposited power distribution inside a layeredlossy medium irradiated by a coupled system of concentrically placedwaveguide applicators

A method is proposed for controlling the deposited power distribution in a layered cylindrical lossy model, irradiated by a phased-array hyperthermia system consisting of four waveguide applicators. A rigorous electromagnetic model of the heated tissue, which takes into account coupling phenomena between system elements, is used for predicting the electric field at any point inside tissue. The relative amplitudes and relative phases of the array elements are optimized in order to attain desired specific absorption rate (SAR) distributions inside and outside malignant tissues. A constrained nonlinear optimization problem is solved by using the penalty function method and the resulting unconstrained minimization of the penalty function is carried out by the downhill simplex method. Two practical phased-array hyperthermia systems have been studied and numerical results are presented