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Biomedical subjects

P R Stauffer

Publications and source records attributed to P R Stauffer.

At least 19 recordsLinked to original sources

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.

Equipment Design↗

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.

Brachytherapy↗

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 degree C-0.2 degree C) and signal sensitivity (0.3 degree C-0.8 degree C/degree C) at all four 500 MHz integration bandwidths tested within the frequency range from 1.2 to 3.0 GHz.

Biomedical Engineering↗

Thermal and SAR characterization of multielement dual concentric conductor microwave applicators for hyperthermia, a theoretical investigation.

Six aperture array dual concentric conductor (DCO) microwave hyperthermia applicators were studied using theoretical models to characterize power deposition (SAR) and steady state temperature distributions in perfused tissue. SAR patterns were calculated using the finite difference time domain (FDTD) numerical method, and were used as input to a finite difference thermal modeling program based on the Pennes Bio-Heat Equation in order to calculate corresponding temperature distributions. Numerous array configurations were investigated including the use of different size DCC apertures (2, 3, and 4 cm), different spacing between apertures (1.0-2.0 cm), and different water bolus thicknesses (5-15 mm). Thermal simulations were repeated using blood perfusion values ranging from 0.5 to 5 kg/m3 s. Results demonstrate the ability of DCC array applicators to effectively and uniformly heat tissue down to a depth of 7.5-10 mm below the skin surface for a large number of different combinations of DCC element size, spacing, and water bolus thickness. Results also reveal the close correlation between SAR patterns and corresponding temperature distributions, verifying that design studies of the applicator can be performed confidently by analysis of SAR, from which the thermal behavior can be estimated. These simulations are useful in the design optimization of large microwave DCC array applicators for superficial tissue heating and for identifying appropriate aperture spacing and bolus thickness parameters for different size DCC aperture arrays and tissue blood perfusion conditions.

Humans↗

Effect of complex bolus-tissue load configurations on SAR distributions from dual concentric conductor applicators. Specific absorption rate.

Power deposition [specific absorption rate (SAR)] distributions from a two-element array configuration of 4-cm-square 915-MHz dual concentric conductor (DCC) microwave antennas were characterized theoretically for several clinically realistic complex bolus-tissue load models using the finite difference time domain (FDTD) numerical method. The purpose of this effort was to determine the perturbing effects on SAR of three often unavoidable heterogeneities in the bolus-tissue load. The three cases studied in this work consist of bone (two ribs spaced 1 cm apart) embedded 5-mm or 1-cm deep in muscle or layered fat-muscle tissue, small air bubbles trapped between the coupling bolus and tissue surface, and variable thickness water bolus layer due to sharply contoured anatomy. Results of the FDTD simulations demonstrate rather small effects on SAR distribution for both rib-sized bones > or = 5-mm deep in muscle and small air pockets < or = 1-mm thick. Larger air bubbles > 1-cm diameter by 3-mm depth showed a distinct concentration of SAR near the lateral sides of the air bubbles, and a blocking effect under the bubbles when located directly under the center of a DCC aperture where there is a higher normal E-field component. Variation from 2.5- to 7.5-mm bolus thickness under the two aperture array produced only minor perturbation of the uniformity and penetration of SAR, along with minor reduction in SAR under the thicker bolus which should be accommodated sufficiently by changes in applied power to the array elements.

Absorption↗

Survival benefit of hyperthermia in a prospective randomized trial of brachytherapy boost +/- hyperthermia for glioblastoma multiforme.

PURPOSE: To determine if adjuvant interstitial hyperthermia (HT) significantly improves survival of patients with glioblastoma undergoing brachytherapy boost after conventional radiotherapy. METHODS AND MATERIALS: Adults with newly-diagnosed, focal, supratentorial glioblastoma < or = 5 cm in diameter were registered postoperatively on a Phase II/III randomized trial and treated with partial brain radiotherapy to 59.4 Gy with oral hydroxyurea. Those patients whose tumor was still implantable after teletherapy were randomized to brachytherapy boost (60 Gy at 0.40-0.60 Gy/h) +/- HT for 30 min immediately before and after brachytherapy. Time to progression (TTP) and survival from date of diagnosis were estimated using the Kaplan-Meier method. RESULTS: From 1990 to 1995, 112 eligible patients were entered in the trial. Patient ages ranged from 21-78 years (median, 54 years) and KPS ranged from 70-100 (median, 90). Most commonly due to tumor progression or patient refusal, 33 patients were never randomized. Of the patients, 39 were randomized to brachytherapy ("no heat") and 40 to brachytherapy + HT ("heat"). By intent to treat, TTP and survival were significantly longer for "heat" than "no heat" (p = 0.04 and p = 0.04). For the 33 "no heat" patients and 35 "heat" patients who underwent brachytherapy boost, TTP and survival were significantly longer for "heat" than "no heat" (p = 0.045 and p = 0.02, respectively; median survival 85 weeks vs. 76 weeks; 2-year survival 31% vs. 15%). A multivariate analysis for these 68 patients adjusting for age and KPS showed that improved survival was significantly associated with randomization to "heat" (p = 0.008; hazard ratio 0.51). There were no Grade 5 toxicities, 2 Grade 4 toxicities (1 on each arm), and 7 Grade 3 toxicities (1 on "no heat" and 6 on the "heat" arm). CONCLUSION: Adjuvant interstitial brain HT, given before and after brachytherapy boost, after conventional radiotherapy significantly improves survival of patients with focal glioblastoma, with acceptable toxicity.

Adult↗

Radiation patterns of dual concentric conductor microstrip antennas for superficial hyperthermia.

The finite difference time domain (FDTD) method has been used to calculate electromagnetic radiation patterns from 915-MHz dual concentric conductor (DCC) microwave antennas that are constructed from thin and flexible printed circuit board (PCB) materials. Radiated field distributions are calculated in homogeneous lossy muscle tissue loads located under variable thickness coupling bolus layers. This effort extends the results of previous investigations to consider more realistic applicator configurations with smaller 2-cm-square apertures and different coupling bolus materials and thicknesses, as well as various spacings of multiple-element arrays. Results are given for practical applicator designs with microstrip feedlines etched on the backside of the PCB antenna array instead of previously tested bulky coaxial-cable feedline connections to each radiating aperture. The results demonstrate that for an optimum coupling bolus thickness of 2.5-5 mm, the thin, flexible, and lightweight DCC antennas produce effective heating to the periphery of each aperture to a depth of approximately 1 cm, and may be combined into arrays for uniform heating of large area superficial tissue regions with the 50% power deposition contour conforming closely to the outer perimeter of the array.

Electric Conductivity↗

Liposomes and hyperthermia in mice: increased tumor uptake and therapeutic efficacy of doxorubicin in sterically stabilized liposomes.

We have shown that sterically stabilized (Stealth) liposomes (SL), can accumulate in the extracellular space within tumors, and may improve pharmacokinetics and therapeutic efficacy of encapsulated doxorubicin (SL-DOX). When SL-DOX were incubated in vitro at different temperatures with 50% bovine serum, approximately 20% of the encapsulated DOX was released at 42 degrees C within 1 min, compared with less than 1% DOX released at 37 degrees C. In vivo, mice were implanted s.c. with C-26 colon carcinoma in both flanks to produce matched tumors 6-10 mm in diameter. Topical hyperthermia treatment consisting of 42 degrees C minimum tumor temperature for 30 min was applied with a microwave device to the tumor on one side only at 1 h after i.v. injection of SL-DOX or free DOX. Tumor DOX concentration in the group which was given injections of SL-DOX and sacrificed 2 h after drug injection was 1.5-fold higher compared with the nonheated tumor in mice given injections of SL-DOX. At 24 h after injection the thermal enhancement ratio for DOX accumulation in tumor remained at 1.5. In addition, there was a 15-fold higher concentration of DOX in tumor from the group given injections of SL-DOX compared to mice given injections of free doxorubicin. To assess therapeutic efficacy, we treated mice with hyperthermia for 15 min either at 1, or at 24 h or at both time points after injection of SL-DOX. We have found that the life span of the group of mice treated with SL-DOX and two 15-min hyperthermia treatments increased 51% compared with control groups receiving the same dosage of SL-DOX but without hyperthermia, and 59% compared to those receiving two hyperthermia treatments but with free DOX. A single hyperthermia treatment either at 1 or 24 h was less effective in increasing life span compared with two treatments, but all groups treated with SL-DOX and single hyperthermia were still superior to the control groups, showing a 27-38% increase in life span.

Animals↗

Practical induction heating coil designs for clinical hyperthermia with ferromagnetic implants.

Interstitial techniques for hyperthermia therapy of cancer continue to evolve in response to requirements for better localization and control over heating of deep seated tissues. Magnetic induction heating of ferromagnetic implants is one of several available techniques for producing interstitial hyperthermia, using thermal conduction to redistribute heat within an array of controlled temperature "hot sources." This report describes seven induction heating coil designs that can be used for producing strong magnetic fields around ferromagnetic seed implants located in different sites in the body. The effect of coil design on the extent and uniformity of the magnetic field is characterized, and appropriate electrostatic shield designs for minimizing electric field coupling to the patient are described. Advantages and disadvantages of each coil type are discussed in terms of the radiated fields, coil efficiency, and ease of use, and appropriate applications are given for each design. This armamentarium of induction coils provides the ability to customize magnetic field distributions for improved coupling of energy into ferromagnetic implant arrays located at any depth or orientation in the body. Proper selection of heating coil configuration should simplify patient setup, improve the safety of patient treatments, and pave the way for future applications of interstitial heating in sites that were previously untreatable.

Equipment Design↗

An improved bolus configuration for commercial multielement ultrasound and microwave hyperthermia systems.

A simple modification is presented for two commercially available hyperthermia applicators which dramatically improves the regulation and dynamic control of the temperature at the bolus/tissue interface. This alteration requires the addition of a variable speed pump, bubble trap, simple heat exchanger, and a few minor changes to the existing system. With this modified design, the water within the bolus is directly circulated and temperature controlled. The convective nature of the circulating system ensures uniform temperature throughout the extended bolus and increases the thermal energy transfer at the bolus/tissue interface. This modification also provides significantly improved flexibility in controlling the treatment temperature distributions since the bolus/tissue interface temperature can now be dynamically varied during a treatment, in addition to adjusting the applicator power output and frequency.

Humans↗

Interstitial thermoradiotherapy with ferromagnetic implants for locally advanced and recurrent neoplasms.

PURPOSE: The University of Arizona, University of California at San Francisco, City of Hope Medical Center, and University of Wisconsin participated in a Phase I/II protocol to assess the heating ability and the toxicity of interstitial thermoradiotherapy using ferromagnetic implantation. METHODS AND MATERIALS: Forty-four patients with advanced primary or recurrent extra-cranial solid malignancies were enrolled in this study. Fourteen gauge catheters were implanted into tumors and, once in the department of Radiation Oncology, loaded with ferromagnetic seeds to deliver a 60 min hyperthermia treatment. Multi-point thermometry was continuously used throughout the heating sessions for all patients, sampling the periphery as well as the core of the tumor. After 192Iridium brachytherapy, 18 patients then had an additional treatment. The mean radiation dose while on protocol was 50.0 Gy, with total doses (including prior radiotherapy) ranging from 20.3-151.8 Gy (median = 88.7 Gy). Response and toxicity were assessed by inspection, palpation, and/or radiologic studies. Forty-one patients were evaluable for response, and there were 55 analyzable hyperthermia treatment sessions. RESULTS: The complete response rate was 61% (25/41). The partial response rate was 31.7% and only 7.3% failed to respond. Median duration of local control has not yet been reached. The mean maximum, minimum, and mean time-averaged temperatures for all in-tissue sensors were 43.7 degrees C, 38.7 degrees C, and 41.0 degrees C, respectively. Tumor size was the only factor significantly correlated with temperatures or with complete response rate; larger tumors attained higher temperatures but smaller tumors had a higher response probability. Nineteen patients (43%) experienced toxicities, however there was only a 7% (3/44) rate of serious complications (Grade 3 or 4). Prior treatment with hyperthermia was the only factor significantly correlated with serious toxicity. CONCLUSION: These results, a 93% total response with only 7% serious toxicity, are encouraging especially in the context of the patient population treated. Phase II/III studies involving ferromagnetic implantation are warranted.

Adult↗

Thermoradiotherapy of recurrent malignant brain tumors.

In an attempt to improve local control and survival over those achieved with brain implant alone, a Phase I/II study of interstitial thermoradiotherapy was undertaken for recurrent malignant gliomas and recurrent solitary brain metastases. Between June 1987 and September 1990, 49 tumors in 48 patients were treated with thermoradiotherapy, including 26 glioblastoma multiforme (GM), 16 anaplastic astrocytomas (AA), 4 adenocarcinomas, and 3 melanomas. Patient age ranged from 18 to 71 years and Karnofsky Performance Status from 40 to 90. Stereotactically implanted catheters were used for both hyperthermia and brachytherapy. Hyperthermia was administered immediately before and after brachytherapy, heating as much of the tumor as possible to 42.5 degrees C for 30 min using helical coil microwave antennas. High-activity iodine-125 sources delivered tumor doses of 32.6 to 63.3 Gy. Complications included reversible neurologic changes in 13 patients, 9 seizures, 4 infections, 1 deep venous thrombosis with pulmonary embolus, and 1 scalp burn. Eighteen patients underwent reoperation for tumor and/or necrosis. Follow-up ranged from 9 to 166+ weeks. The median follow-up for living patients with GM and AA was 37 weeks and 92 weeks, respectively. Actuarial median survival was 47 weeks for patients with GM. For patients with AA, actuarial survival was 65% at 18 months and median survival has not yet been reached. Multivariate analysis showed a strong correlation between freedom from local tumor progression and "T90" temperature or minimum tumor temperature. Interstitial brain thermoradiotherapy is now being evaluated in a randomized Phase II trial for previously untreated GM.

Adenocarcinoma↗

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

A highly localized burst of energy applied to the myocardium via a transvenous catheter-mounted power source can be used to destroy endocardial tissue regions which mediate life-threatening arrhythmias. In the past, high-voltage direct current pulses, radio-frequency (RF) current, and laser light have been used as energy sources. In this paper, the use of 2450 MHz microwave energy applied via a miniature coaxial cable-mounted helical coil antenna designed specifically for this application was investigated as a means to increase the treated volume of cardiac tissue in a controllable and efficient 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 in terms of the radial penetration and overall volume of heated tissue. Heating patterns from the RF electrodes dropped off much more abruptly both radially and axially than the microwave antenna such that 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.

Catheter Ablation↗

Treatment planning for ferromagnetic seed heating.

Computer simulations of ferromagnetic seed heating have been performed for the case of a single constant-temperature ferromagnetic seed. Results obtained from both 2-dimensional and 3-dimensional thermal models are compared to determine the appropriate use and limitations of the 2-dimensional model for the case of array implants. It has been determined that the 2-dimensional model that assumes infinite extent of the ferromagnetic seed(s) is applicable for calculating the thermal distribution in any plane perpendicular to the axes of the implant(s) up to 1 cm from the ends of the seed(s). The feasibility of spatially interspersed ferromagnetic and radioactive seeds for concurrent hyperthermia and brachytherapy has also been studied. The steady-state temperature distribution within an array of ferromagnetic seed implant has been examined as a function of implant spacing and blood perfusion rate. The results have been quantified in generalized histograms that are readily applicable to pre-treatment planning.

Computer Simulation↗

Interstitial irradiation and hyperthermia for the treatment of recurrent malignant brain tumors.

Between June 1987 and June 1989, 29 recurrent malignant gliomas or recurrent solitary brain metastases in 28 patients were treated in a Phase I study of interstitial irradiation and hyperthermia. Patient age ranged from 18 to 65 years, and the Karnofsky Performance Status scores ranged from 40 to 90%. There were 13 glioblastomas, 10 anaplastic astrocytomas, 3 melanomas, and 3 adenocarcinomas. Catheters were implanted stereotactically after computed tomography-based preplanning. Hyperthermia was administered before and after brachytherapy, using one to six 2450- or 915-MHz helical coil microwave antennas and one to three multisensor fiberoptic thermometry probes. The goal was to heat as much of the tumor as possible to 42.5 degrees C for 30 minutes. Within 30 minutes after the first hyperthermia treatment, implant catheters were afterloaded with high-activity iodine-125 seeds delivering tumor doses of 32.6 to 61.0 Gy. Most patients had no sensation of heating. Complications included seizures in 5 patients, reversible neurological changes in 9 patients, a scalp burn in 1, and infections in 3. Of 28 evaluable 2-month follow-up scans, 11 showed definite improvement in the radiological appearance of the tumor, 4 were slightly improved, 7 were stable, and 6 showed tumor progression. Ten patients underwent reoperation for persistent tumor and/or necrosis. Eleven of 28 patients are alive 40 to 97 weeks after treatment. Thirteen patients died of a brain tumor, 2 died of extracranial melanoma metastases, 1 died of new brain melanoma metastases, and 1 died of a pulmonary embolus. The median survival was 55 weeks overall. Median survival has not yet been reached for the anaplastic astrocytoma subgroup. We conclude that interstitial brain hyperthermia using helical coil microwave antennas is technically feasible. The level of toxicity is acceptable, and the computed tomographic response rate is encouraging.

Adenocarcinoma↗

31P magnetic resonance spectroscopy of animal uveal melanoma.

Scleral surface coils were used to obtain in vivo magnetic resonance spectra (MRS) of Greene melanoma implanted in the rabbit uvea. Well-localized tumor spectra (4.7 Tesla) with good signal-to-noise ratios (S/N) were obtained from the tumor with a "single-pulse" sequence in less than 1 hour. Tumor localization was confirmed with one-dimensional spectroscopic imaging studies. Serial 31P spectra were obtained during tumor growth and after both optimal and suboptimal hyperthermia. Early 31P MRS change is correlated with tumor treatment response and preceded histologic evidence of cell destruction. Twenty-four to 48 hours after successful treatment, the inorganic phosphate/nucleoside triphosphate (NTP), and phosphomonoester/NTP ratios were significantly increased from 1.2 +/- 0.1 to 1.7 +/- 0.1 and 1.3 +/- 0.1 to 1.8 +/- 0.2, respectively. In contrast, untreated or ineffectively treated tumors showed little change. Interpretation of 31P MRS data in this animal uveal melanoma model after the first week was complicated by decreased S/N, increased contamination from contiguous tissues, ingrowth of fibroblasts, macrophages, and intratumor hemorrhage.

Animals↗

Microwave hyperthermia for choroidal melanoma in rabbits.

Radiation has provided excellent local control rates in choroidal melanoma, but significant impairment in visual acuity has occurred in 30-60% of patients due in part to the development of radiation vasculopathy in the fovea and optic disc. Hyperthermia has been shown to have a synergistic effect when added to radiation therapy in human malignancies. The use of hyperthermia in ocular melanoma may allow a reduction in the total radiation dose necessary to achieve local control. A 2450-MHz microwave plaque applicator with integral surface cooling was used to deliver hyperthermia treatments to rabbit eyes containing choroidal melanomas. Extensive thermal mapping was done in acute eyes. In 18 survival animals, a single 23-G needle thermocouple probe with three sensors was inserted into the tumor. Target temperatures of 41.0-46.0 degrees C were maintained for 1 hour. All tumor-bearing eyes were followed for 1 month after treatment, or until tumor growth was noted, with serial ultrasound measurements and visual examinations. A 92% response rate was obtained in tumors treated at temperatures greater than 43.0 degrees C for 1 hour with no significant toxicity. Heat alone has significant tumoricidal properties in this animal model.

Animals↗