Paul R. Stauffer

Evaluation of microwave and radio frequency catheter ablation in a myocardium-equivalent phantom model

The use of 2450-MHz microwave energy applied via a miniature coaxial cable-mounted helical coil antenna was investigated as a means to increase the treated volume of cardiac tissue in a saline-perfused, tissue-equivalent manner during ablation. Using an array of fiber-optic temperature probes implanted in a saline-perfused, tissue-equivalent gel phantom model designed to simulate the myocardium during ablation, the heating pattern from the microwave antenna was characterized and compared to that induced by a commercial RF electrode catheter at 550 kHz. Effects of variable contact angle between the heat source and heart wall were assessed. Heating patterns from the RF electrodes dropped off much more abruptly both radially and axially than the microwave antenna. The volume of effectively heated tissue was more than ten times larger for the microwave antenna when the heat sources were well-coupled to the tissue, and more than four times larger for the microwave antenna when the sources were angled 30 degrees away from the tissue surface.<<ETX>>

Magnetic Induction Heating of Ferromagnetic Implants for Inducing Localized Hyperthermia in Deep-Seated Tumors

A variable frequency magnetic induction heating system has been developed for localized hyperthermic treatment of deep-seated tumors via power deposition into arrays of 1-2 mm diameter ferromagnetic cylindrical implants. The frequency dependence of implant heating compared to that induced directly into tissues indicates use of frequencies below 4 MHz. Above 10 MHz, tissues are heated directly from the induced eddy currents. Thermographic analyses of temperature distributions induced in tissues equivalent phantom models and in exposed animal tissues in vivo have been performed for several implant materials and array configurations. Results of the thermal dosimetry show that the majority of tissue contained within multiimplant arrays can be heated such that the temperature rises to 55-70 percent of the implant temperature differential. The resulting tissue temperature distribution is dependent on local blood flow and array characteristics, but not significantly on tissue electrical properties. Operating the system at 1.9. MHz, we demonstrate that it is possible to raise an implanted volume to therapeutic temperatures safely, in less than 10 min, with little increase in temperature outside the array boundaries.

Sonophoresis. I. The Use of High-Frequency Ultrasound to Enhance Transdermal Drug Delivery

Previous attempts to use ultrasound (≤1-MHz frequency and 1 to 3-W/cm2 intensity) to enhance transdermal drug delivery (so-called sonophoresis) have produced inconsistent results. Theoretical analysis of ultrasound propagation in tissue predicts that higher-frequency ultrasound (>1 MHz) will increase the concentration of energy deposition in the stratum corneum (SC) (typically, the rate-limiting barrier to percutaneous penetration). This hypothesis was tested by comparing the passive transdermal delivery of salicylic acid with that under the influence of ultrasound at 2-, 10-, and 16-MHz frequency; measurements were performed in vivo in hairless guinea pigs. Total drug absorbed was quantified by determining the amount of salicylic acid (1) present in SC tape strips and (2) eliminated in urine. Sonophoresis for 20 min at 2 MHz caused no significant increase in salicylic acid delivery over passive diffusion; treatment with ultrasound at 10 and 16 MHz, on the other hand, significantly elevated salicylic acid transport, by 4-fold and 2.5-fold, respectively. Kinetic analysis of the sonophoretic data at 10 and 16 MHz also revealed that the diffusion lag time associated with transdermal drug delivery (TDD) was reduced. A shorter period (5 min) of sonophoresis again resulted in enhanced TDD (relative to the corresponding control) at the higher frequencies; the delivered dose, and the level of enhancement, however, were lower than those after the 20-min treatment. In a separate series of experiments, it was shown that (a) ultrasound did not alter the release kinetics of salicylic acid from the gel formulation used and (b) pretreatment of the skin with ultrasound at 10 and 16 MHz lowered skin barrier function such that the subsequent delivery of salicylic acid was enhanced compared to passive transport without sonophoresis pretreatment. It follows that the enhancing effect of sonophoresis is due to a direct effect of ultrasound on (presumably) the stratum corneum.

Observations on the Use of Ferromagnetic Implants for Inducing Hyperthermia

Magnetic induction heating of ferromagnetic implants can be used to produce highly localized hyperthermia in deep seated tumors. We discuss the physical parameters which characterize this method and give illustrations from initial clinical investigations in animals. The physical parameters studied include magnetic field strength, frequency, load size, field uniformity, coil designs, and the heating potential of implant materials and configurations. Calculations consistent with our experimental results predict a maximum heating frequency of the order of 500 kHz for large cross-sectional loads, such as the human abdomen, and 1.9 MHz for smaller loads, such as the human brain. An experlhnental technique is introduced for accurate quantitative evaluation of the heating potentials of ferromagnetic materials in a gelled phantom medium. These data are analyzed in terms of heating efficiency per unit implant length (¿L), which is itself a function of implant length, diameter, annealed state, and orientation with respect to the magnetic field. A spiral sheet coil design is described and recommendations are given for proper E-Field shielding of induction coils for clinical applications. A brief discussion of techniques of implanting the ferromagnetic materials is also given. Finally, several in vivo animal studies are presented to illustrate the use of the technique for treating tumors in pelvis, thorax, oral-pharynx, and brain.

RTOG quality assurance guidelines for clinical trials using hyperthermia.

M. W. DEWHIRST, D.V.M., PH.D.,* T. L. PHILLIPS, M.D.,+ T. V. SAMULSKI, PH.D.,+ P. STAUFFER, MSEE,? P. SHRIVASTAVA, PH.D.,+ B. PALIWAL, PH.D.,+ T. PAJAK, PH.D.,+ M. GILLIM, PH.D.,+ M. SAPOZINK, M.D., PH.D.,+ R. MYERSON, M.D., PH.D.,+ F. M. WATERMAN, PH.D.,+ S. A. SAPARETO, PH.D.,+ P. CORRY, PH.D.,+ T. C. CETAS, PH.D.,+ D. B. LEEPER, PH.D.,+ P. FESSENDEN, PH.D.,+ D. KAPP, M.D., PH.D.,+ J. R. OLESON, M.D., PH.D.+ AND B. EMAMI, M.D.*

Evolving technology for thermal therapy of cancer

This paper is intended as a succinct review of technology used for clinical hyperthermia therapy for cancer, as culled from a presentation at the special workshop on Thermal Medicine, Heat Shock Proteins, and Cancer at the Society for Thermal Medicine conference in Spring 2005. Following a brief overview of thermal therapy treatment options and available mechanisms for heating tissue, the paper focuses on the evolution of equipment from basic single element heating devices of the early 1980s to adjustable multi-element heating devices currently in use or in final stages of development. Representative devices from the past, present and near future are cited for further investigation by the interested reader. The paper concludes with a summary of general trends in the evolution of clinical hyperthermia techniques and a statement of current challenges remaining for the field.

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 (^9; r ) of freshly excised human liver tumour was 12% higher than that of surrounding normal liver, and the electrical conductivity (`3;) 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 `3; rising only 1.1%/°C in porcine liver (15-37°C) and 2.0%/°C in bovine liver (10-90°C), and ^9; r decreasing Ͱ4;0.2%/°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.

Dual-mode antenna design for microwave heating and noninvasive thermometry of superficial tissue disease

Hyperthermia therapy of superficial skin disease has proven clinically useful, but current heating equipment is somewhat clumsy and technically inadequate for many patients. The present effort describes a dual-purpose, conformal microwave applicator that is fabricated from thin, flexible, multilayer printed circuit board (PCB) material to facilitate heating of surface areas overlaying contoured anatomy. Preliminary studies document the Feasibility of combining Archimedean spiral microstrip antennas, located concentrically within the central region of square dual concentric conductor (DCC) annular slot antennas. The motivation is to achieve homogeneous tissue heating simultaneously with noninvasive thermometry by radiometric sensing of blackbody radiation from the target tissue under the applicator. Results demonstrate that the two antennas have complimentary regions of influence. The DCC ring antenna structure produces a peripherally enhanced power deposition pattern with peaks in the outer corners of the aperture and a broad minimum around 50% of maximum centrally. In contrast, the Archimedean spiral radiates (or receives) energy predominantly along the boresight axis of the spiral, thus confining the region of influence to tissue located within the central broad minimum of the DCC pattern. Analysis of the temperature-dependent radiometer signal (brightness temperature) showed linear correlation of radiometer output with test Load temperature using either the spiral or DCC structure as the receive antenna. The radiometric performance of the broadband Archimedean antenna was superior compared to the DCC, providing improved temperature resolution (0.1/spl deg/C-0.2/spl deg/C) and signal sensitivity (0.3/spl deg/C-0.8/spl deg/C//spl deg/C) at all four 500 MHz integration bandwidths tested within the frequency range from 1.2 to 3.0 GHz.

Introduction: thermal ablation therapy.

The diseases which medicines cannot cure, excision cures: those which excision cannot cure, are cured by the cautery; but those which the cautery cannot cure, may be deemed incurable (Hippocrates Aphorisms, 400 BCE).

Catheter ablation of the atrioventricular junction using a helical microwave antenna: a novel means of coupling energy to the endocardium.

Catheter ablation with either direct current defibrillator discharges or radiofrequency energy produces tissue injury via current flow from an electrode into the adjacent myocardium. In order to affect tissue at a distance, excessive power density may be produced at the electrode‐tissue interface with the possibility of explosive gas formation or coagulum formation. A novel microwave catheter was developed with a helical antenna distally. This coil, although not in direct contact with the endocardium, radiates an electromagnetic field into the tissue that, in turn, causes thermal injury. The utility of this system for ablation was assessed in six dogs. The antenna catheter was introduced percutaneously and positioned so as to record the largest His electrogram. Microwave power (50 watts at 2,450 MHz) was applied for 114 ± 118 seconds. Complete AV block was produced in all six animals with 1.8 ± 1.2 applications. There was no ventricular ectopy or change in blood pressure during microwave ablation. One dog died 6 days after ablation. The remaining five dogs had persistent, complete AV block during 6 weeks of follow‐up. Pathological analysis at 6 weeks revealed a large (mean 2.8 ± 4.7 mm) fibrovascular scar in the region of the AV junction. Percutaneous microwave ablation of the endocardium appears feasible, By radiating an electromagnetic field without direct contact, this system can produce large lesions without being limited by desiccation of tissue and impedance rise.