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Biomedical subjects

T P Ryan

Publications and source records attributed to T P Ryan.

At least 19 recordsLinked to original sources

Factors influencing electrovaporization in the treatment of benign prostatic hyperplasia.

Electrovaporization refers to the process of vaporizing tissue using electrical energy. Proposed as a new treatment method for benign prostatic hyperplasia (BPH), this technique allows removal of prostatic tissue with simultaneous coagulation, thereby minimizing blood loss. The recent increase in popularity of electrovaporization in the treatment of BPH warrants a quantitative assessment of the process, including an objective evaluation of its influencing factors. In this study, the effects of power, mechanical loading, and excursion rate on tissue removal by electrovaporization were examined in fresh skeletal muscle. A monopolar electrode was attached to the weighted arm of a linear motion system and rolled across the tissue surface while activated by a radio-frequency generator. The tissue samples were frozen and cut longitudinally to allow visualization and measurement of the vaporized groove using an optical imaging technique. The volume of tissue removed increased significantly when power was increased from 120 to 150 W (46 to 119 mm3, p = 0.006), when the load was increased from 20 to 50 gm (20 to 119 mm3, p = 0.002), and when the excursion rate was decreased from 25 to 15 mm/s (29 to 69 mm3, p < 0.05) and from 15 to 10 mm/s (69 to 137 mm3, p < 0.05). There was no significant gain in volume removed when power was increased to 180 W or when the load was increased to 70 gm, indicating that these factors are constrained with regard to optimal tissue removal. Using a novel method to quantitatively assess tissue removal by electrovaporization, this study has demonstrated that greater tissue removal can be achieved by increasing power, increasing the load, or decreasing the excursion rate, but only within limits.

Animals

Tissue impedance as a function of temperature and time.

Tissue impedance dependence on temperature has been measured for six tissue types. The information was gathered using an automated laboratory under computer control. This information is needed to be able to input these values into a computer model that predicts temperature distribution produced by delivery of radio frequency energy. Due to the thermal dose of time and temperature, tissue properties change and no published data are available that document this. Since there are no theoretical predictions, empirical data were measured to supply this information. Using an aluminum cylindrical cavity of volume 1.69 cm3, muscle, liver, brain, and fat tissue impedance were measured at 500 kHz over a range of temperatures. All tests began at room temperature where baseline measurements were made. The cylinder was then placed in a constant temperature water bath at between 30 and 90 degrees C. The tests were run for a period of 10 to 30 minutes. Temperature homogeneity was carefully studied throughout the volume of the cylinder. It was found that thermal equilibrium occurred within four minutes. Special care was taken with the tissue sample in regard to optimize moisture and freshness, and minimize fat content. Grain orientation was also taken into consideration depending on the test. For all tissue types, resistivity decreased initially as the sample temperature equilibrated with the bath temperature. For temperatures less than 75 degrees C, resistivity values remained approximately constant over time.

Adipose Tissue

Diquat-dependent protein carbonyl formation. Identification of lipid-dependent and lipid-independent pathways.

In a previous report on diquat-dependent oxidative damage in rat hepatic microsomes, protein oxidation, as measured by protein carbonyl (PC) formation, was observed in addition to lipid peroxidation (LP). Both phenomena were antioxidant sensitive. Inhibition of PC formation was somewhat surprising given the proposed mechanism of metal-catalyzed protein oxidation. Studies reported here examined diquat-dependent PC formation in greater detail. In rat hepatic microsomes, diquat-dependent thiobarbituric acid-reactive substances (TBARS) and PC formation were time and concentration dependent. In this system, LP was inhibited completely by U-74006F or U-78517G, whereas PC formation was inhibited only partially by these antioxidants. In an essentially lipid-free system consisting of purified rat hepatic cytochrome P450 reductase, BSA and an NADPH-generating system, PC formation was also observed, but was not antioxidant-sensitive. Under these conditions, minimal diquat-dependent TBARS formation was observed. The observation of relative antioxidant insensitivity is consistent with H2O2 (generated during the diquat redox cycle) catalyzing protein oxidation via a site-specific, metal-catalyzed mechanism. Thus, different pathways would appear to be involved in diquat-dependent PC formation in lipid-containing and lipid-free systems. Carbon tetrachloride induces LP following reductive activation to the trichloromethyl free radical, a pathway not directly involving H2O2 generation. In the microsomal system, CCl4 induced TBARS and PC formation, both of which were completely inhibitable by antioxidants. Taken together, these data suggest that diquat induces PC formation by lipid-dependent (antioxidant-sensitive) and lipid-independent (antioxidant-insensitive) pathways. In microsomes, both pathways contribute to diquat-dependent PC formation. Data for the lipid-independent pathway are consistent with the mechanism of metal-catalyzed protein oxidation proposed by Stadtman and colleagues (reviewed in Free Radic Biol Med 9: 315-325, 1990), while the lipid-dependent pathway is likely secondary to LP itself--via a Michael-type addition reaction between hydroxyalkenals and protein sulfhydryl groups, amino groups or other protein nucleophiles. The latter pathway is also responsible for carbon tetrachloride-dependent PC formation. Additional studies are in progress to further characterize the lipid-independent mechanism.

Animals

Brain hyperthermia: I. Interstitial microwave antenna array techniques--the Dartmouth experience.

PURPOSE: Microwave antennas of various designs were inserted into arrays of nylon catheters implanted in brain tumors with the goal of raising temperatures throughout the target volume to 43.0 degrees C. METHODS AND MATERIALS: All antennas were flexible, and included dipole, choke dipole, modified dipole, and helical designs driven at 915 or 2450 MHz. Antennas were tested in brain-equivalent phantom in arrays. Phase shifting and phase rotation techniques were incorporated into the treatment system to steer power in the tumor, assisted by a treatment planning computer that predicted power deposition patterns and temperature distributions. Choke antennas were designed and tested to reduce a dependence of the central power location on depth of insertion into tissue. Temperature data analysis used only central and orthogonal axes mapping data measured at 2.0 mm intervals. RESULTS: A total of 23 patients were treated, using from one to six microwave antennas. Minimum tumor temperatures, averaged over the 60 min treatment, ranged from 37.2-44.3 degrees C (mean 40.0 degrees C) and maximum average tumor temperatures ranged from 46.5-60.1 degrees C (mean 49.1 degrees C). The percentage of all measured temperatures reaching therapeutic levels (> or = 43.0 degrees C) was 70.9. T90, the temperature at which 90% of all measured temperatures equaled or exceeded, was 40.8 degrees C, and T50 was 44.2 degrees C. CONCLUSION: Patient data analysis showed that the array of four dipole antennas spaced 2.0 cm apart were capable of heating a volume of 5.9 cm (along the central array axis) x 2.8 cm x 2.8 cm.

Brain Neoplasms

Theoretical and experimental analysis of air cooling for intracavitary microwave hyperthermia applicators.

An intracavitary microwave antenna array system has been developed and tested for the hyperthermia treatment of prostate cancer at Thayer School of Engineering and Dartmouth-Hitchcock Medical Center. The antenna array consists of a choked dipole antenna inserted into the urethra and a choked dipole antenna eccentrically embedded in a Teflon obturator inserted into the rectum. To prevent unnecessary heating of the healthy tissue that surrounds each applicator, an air cooling system has been incorporated into the rectal applicator. The air cooling system was designed and modeled theoretically using a numerical solution of heat and momentum equations within the applicator, and an analytical solution of the Pennes bioheat equation in tissue surrounding the applicator. The 3-D temperature distribution produced by the air-cooled rectal applicator was measured in a perfused canine prostate.

Animals

Inhibition of in vitro lipid peroxidation by 21-aminosteroids. Evidence for differential mechanisms.

In a previous report (Ryan and Petry, Arch Biochem Biophys 300: 699-704, 1993), the effects of two 21-aminosteroids (U-74500A and U-74006F) on the oxidation and reduction of iron in a buffer/organic solvent system were investigated. In those studies, U-74500A was found to be an efficient iron reductant and potential iron chelator, whereas U-74006F had little effect on iron redox chemistry. As an extension of those studies, we now report the effects of U-74006F and U-74500A on lipid peroxidation in systems that are dependent upon iron oxidation/reduction. In liposomes, U-74500A inhibited ADP:Fe(II)-dependent lipid peroxidation in a concentration-dependent manner, whereas U-74006F was minimally effective in this system. The mechanism of U-74500A-dependent inhibition probably involved interactions with iron, as iron oxidation was inhibited in the presence of this compound. No effects on iron oxidation were observed in the presence of U-74006F. Addition of Ferrozine to liposomal incubation mixtures indicated that at least two iron pools were present in samples containing U-74500A, one immediately bound by Ferrozine, and another that was bound more slowly. Furthermore, ADP:Fe(III)/ascorbate-dependent lipid peroxidation was blocked completely by U-74500A, presumably by formation of a redox inert complex upon reduction of the iron. U-74500A partially protected ADP:Fe(II) from oxidation by H2O2 and lipid hydroperoxides, indicating that the U-74500A:iron complex was stable in the presence of biologically relevant oxidants. U-74006F did not markedly affect iron oxidation or reduction when incorporated into phospholipid liposomes. In microsomal lipid peroxidation systems containing ADP:Fe(III) and NADPH, both U-74500A and U-74006F inhibited lipid peroxidation. U-74006F-dependent inhibition of microsomal lipid peroxidation was dependent on both NADPH and Fe(III). Further, it was enhanced when U-74006F was allowed to preincubate in this system prior to iron addition. Preincubation of U-74006F with microsomes, NADPH, and ADP:Fe(III) produced several metabolites detectable by HPLC. These results suggest that U-74500A inhibits lipid peroxidation by directly affecting iron redox chemistry, whereas U-74006F-mediated inhibition is enhanced by preincubation with a metabolically competent microsomal system.

Animals

The effects of 21-aminosteroids on the redox status of iron in solution.

The effects of two 21-aminosteroids (U-74500A and U-74006F) on the oxidation and reduction of iron were investigated. U-74500A completely prevented ADP: Fe(II) autoxidation whereas U-74006F had only a slight inhibitory effect. The inhibition of Fe(II) oxidation by U-74500A was concentration dependent, with 100% inhibition occurring at concentrations equal to or greater than 25 microM in systems containing 50 microM Fe(II). When the Fe(II)-specific chelator Ferrozine was added to incubations containing U-74500A and ADP:Fe(II), formation of the Ferrozine:Fe(II) chromophore was slow, suggesting that U-74500A chelates Fe(II) with substantial affinity. Temporally, 20 min were required for complete formation of the Ferrozine-Fe(II) chromophore in the presence of U-74500A, whereas complexation in its absence was instantaneous. This phenomenon was not observed with U-74006F, Desferal, or ascorbate. In a system containing 25 microM ADP:Fe(II), U-74500A (25 microM) and U-74006F (25 microM) acted as iron reductants, reducing the iron at rates of approximately 2, and 0.1 microM/min, respectively. In addition, U-74500A fluorescence was quenched in a concentration-dependent manner upon the addition of Fe(III), further demonstrating interactions between this compound and iron. The substructures of U-74500A consist of a steroid (U-76911) and a complex amine (U-82902E). When these compounds were assayed individually, it was found that U-82902E exhibited activities similar to those of U-74500A, whereas the free steroid had no effect. Studies employing cyclic voltammetry revealed that U-74500A had a relatively low oxidation potential (E = 228 mV), whereas U-74006F was much less susceptible to oxidation (E = 810 mV). Taken together, these data suggest that subtle effects on iron redox chemistry, which would in turn inhibit or eliminate the initiation of undesired oxidative reactions, may contribute to the potent antioxidant activities of U-74500A and U-74006F.

Adenosine Diphosphate

The role of metals in the enzymatic and nonenzymatic oxidation of epinephrine.

The effects of transition metals on nonenzymatic and ceruloplasmin catalyzed epinephrine oxidation were investigated by studying rates of epinephrine oxidation in purified buffers and in the presence of metal chelating agents. We found that epinephrine does not "autoxidize" in sodium chloride solutions prepared with deionized water that was further purified by chromatography over Chelex 100 resin prior to use. Epinephrine was oxidized rapidly in sodium chloride prepared with tap water (1.20 +/- 0.12 nmoles/min) or in deionized water (0.40 +/- 0.80 nmoles/min), but this oxidation was prevented by the addition of Desferal, a potent metal chelating agent. Epinephrine oxidation was enhanced upon the addition of ceruloplasmin, and this oxidation rate could be slowed, but not eliminated, by the addition of Desferal. If epinephrine solutions were preincubated for 72 hours with Desferal prior to ceruloplasmin addition, however, no oxidation was observed. Epinephrine was shown to form colored complexes with both iron and copper at pH 7.0. The Fe(III)-epinephrine complex was much more stable than was the Cu(II)-epinephrine complex. Oxygen consumption studies of ceruloplasmin catalyzed epinephrine oxidation showed that copper was a better promoter of epinephrine oxidation than was iron, suggesting that ceruloplasmin-catalyzed epinephrine oxidation results from adventitious copper bound to the purified enzyme. In light of these results, the physiological relevance of ceruloplasmin catalyzed oxidation of biogenic amines may be minor.

Biogenic Monoamines

Rat ceruloplasmin: resistance to proteolysis and kinetic comparison with human ceruloplasmin.

Rat ceruloplasmin was purified from serum using fast protein liquid chromatography and compared to human ceruloplasmin isolated in the same manner. Rat ceruloplasmin was found to be more resistant to plasmin-mediated proteolysis than was human ceruloplasmin. Although both proteins were cleaved initially to products with apparent molecular weights of 116,000 and 20,000 Da, rat ceruloplasmin was resistant to further proteolysis, whereas the human enzyme was cleaved to smaller fragments. Primary structure differences could account for the different relative stabilities between the two enzymes. Kinetic analysis of rat ceruloplasmin produced a biphasic v vs v/s plot with apparent Km's of 40 and 1.5 microM for iron. When compared with the human enzyme, rat ceruloplasmin showed about one-fourth the ferroxidase activity and had a much broader pH profile than that of human ceruloplasmin. Rates of p-phenylenediamine oxidation by rat ceruloplasmin were about one-half those obtained with human ceruloplasmin, with maximal p-phenylenediamine oxidase activity at pH 5.0 for both enzymes.

Amino Acid Sequence

Interstitial microwave hyperthermia and brachytherapy for malignancies of the vulva and vagina. I: Design and testing of a modified intracavitary obturator.

A vaginal obturator was fabricated to be used in combination with implanted catheters to provide microwave hyperthermia and brachytherapy to the vulva and vaginal wall. This site is difficult to heat or irradiate solely with interstitial techniques. The obturator was modified to provide grooves for the mounting of interstitial catheters into the outer wall and was matched with a template for circumferential implants. Power deposition tests were done using arrays of three microwave antenna designs: dipole (hA = hB = 3.9 cm), helical (3.9 cm coil, shorted), and modified dipole (1.0 cm helix on dipole tip) to test the performance of the obturator. The obturator and four non-obturator catheters were positioned in muscle-equivalent phantom. Two obturator catheters along with two free-standing catheters formed the obturator array. Four freestanding catheters formed the non-obturator array. Power deposition or specific absorption rate (SAR) measurements were made along the central axis, bisect, and diagonal transect of each array. SAR results showed that antennas in the obturator wall radiated as dipole theory predicts, although with less power density when compared to antennas in the same catheters spaced 1.8 cm from the obturator. This could be compensated for by increasing the power to the antennas in the obturator by 42%. Adjacent pairs of antennas were placed 90 degrees out of phase for 0.25 sec and rotated around the array. Phase rotation demonstrated that the central array SAR peaks could be lowered from 100% to 50% SAR, with dipole antennas thus resulting in lowered peak temperatures and the ability to heat larger volumes by improving the distribution of power. With helical antennas, there was 50% SAR at the array center when operated coherently without phase rotation. Three patients were treated with the obturator and a custom-made template using dipole antennas, and temperatures were measured in five obturator catheters. Therapeutic heating was measured in the catheters on the obturator between antennas in contact with the vaginal mucosa.

Brachytherapy

Three-dimensional theoretical temperature distributions produced by 915 MHz dipole antenna arrays with varying insertion depths in muscle tissue.

Interstitial microwave antenna array hyperthermia (IMAAH) systems are currently being used in the treatment of cancer. The insertion depth of an interstitial microwave antenna, defined as the length of the antenna from the tip to the point of insertion in tissue, affects its ability to produce uniform power deposition patterns in tumor volumes. The effect of varying insertion depths on the ability of an IMAAH system to heat two theoretical tumor models was examined. Four dipole microwave antennas were implanted in a 2 x 2 cm array and driven at 915 MHz in muscle tissue. The explicit power deposition patterns were calculated for each insertion depth using known theory. The bioheat transfer equation was solved for the 3-dimensional steady-state temperature distributions in cylindrical and ellipsoidal tumor models using a finite element method. Homogeneous and nonhomogeneous blood flow models were considered. As a basis of comparison of the various temperature distributions, the volume of tumor heated to greater than or equal to 43 degrees C was calculated. Under the conditions of this study, the insertion depth was shown to have a significant effect on the ability of an IMAAH system to heat the tumor volumes. A sharp decrease in the percentage of tumor volume heated to greater than or equal to 43 degrees C was seen for insertion depths between 7.8 and 14.6 cm. At an insertion depth of 11.7 cm (3/4 lambda) there was virtually no heating of the tumor. Regions of elevated power occurred outside of the desired treatment volume, stressing the importance of adequate thermometry techniques and demonstrating the need for hyperthermia treatment planning prior to implantation of an antenna array. Plots of the power deposition patterns and the corresponding temperatures produced in the diagonal plane of the antenna arrays are present.

Equipment Design

The role of iron in oxygen-mediated toxicities.

The transition metal iron is capable of catalyzing redox reactions between biomolecules and oxygen that would not occur if catalytically active iron were not present. Although these biological oxidations (which are known collectively as "oxidative stress") have been implicated in numerous toxicities, the exact role of the iron catalyst remains to be elucidated. This review focuses on our current understanding of the role of iron in oxidative stress, discussing biologically relevant sources, biochemical forms, and reaction mechanisms of iron as a catalyst of biomolecular oxidations. Specific toxicities in which alterations in normal iron metabolism is thought to overwhelm the body's antioxidant defense system are presented, and future treatment regimens involving novel antioxidant drugs are discussed.

Arteriosclerosis

Design of an automated temperature mapping system for ultrasound or microwave hyperthermia.

An automated temperature mapping system was designed to accomplish the following goals: remote control mapping; a maximum position error of 0.5 mm; mapping simultaneously on several channels; real-time screen display on a dedicated computer; to be inexpensive, and have a simple patient interface and set up. A four channel, microstepper system was fabricated for less than $1000 and controlled by an IBM-AT computer. The system utilizes direct drive of Luxtron fibre-optic probes fed through thin flexible Teflon tubing which allows for patient movement. The driving and control software were written in the programming language "C". Mapping parameters for each independent channel include start and stop positions and map increment. The software permits the user to automatically find the maximum temperature along a track in three passes of 2.0, 1.0 and 0.5 mm steps. The latter two passes take five or seven readings centred about the maximum of the previous pass. A high resolution monitor plots the temperatures in real time, overlaying the previous map in a new colour. A screen dump was written to drive a colour printer with the plot information. The computer evaluates each plot to safeguard against any shift in the maximum location. Visualization of orthogonal pullbacks provides rapid feedback and aids in the repositioning of superficial hyperthermia transducers. The time saved over the previous manual mapping methods easily justifies the additional set up time.

Animals

Experimental brain hyperthermia: techniques for heat delivery and thermometry.

An experimental canine brain model was developed to assess the effects of hyperthermia for a range of time and temperature endpoints, delivered within a specified distance of an interstitial microwave antenna in normal brain. The target temperature location was defined radially at 5.0 or 7.5 mm from the microwave source at the longitudinal location of maximum heating along the antenna in the left cerebral cortex. Temperatures were measured with fiberoptic probes in a coronal plane at this location in an orthogonal catheter at 1.0 mm intervals. Six antennas were evaluated, including dipole, modified dipole, and four shorted helical antennas with coil lengths from 0.5 to 3.9 cm. Antenna performance evaluated in tissue equivalent phantom by adjusting frequency at a fixed insertion depth of 7.8 cm or adjusting insertion depth at 915 MHz showed dipoles to be much more sensitive to insertion depth and frequency change than helical antennas. Specific absorption rate (SAR) was measured in a brain/skull phantom and isoSAR contours were plotted. In vivo temperature studies were also used to evaluate antenna performance in large and small canine brain tissues. A helical antenna with a 2.0 cm coil length driven at 915 MHz was chosen for the beagle experiments because of tip heating characteristics, well-localized heating along the coil length, and heating pattern appropriate to the smaller beagle cranial vault. Verification of lesion dimensions in 3-D was obtained by orthogonal MRI scans and histology to document the desired heat effect, which was to obtain an imagable lesion with well-defined blood-brain-barrier breakdown and necrotic zones. The desired lesion size was between 1.5 to 2.5 cm diameter radially, in the coronal plane with the greatest diameter.

Animals

Comparison of six microwave antennas for hyperthermia treatment of cancer: sar results for single antennas and arrays.

Interstitial techniques of inserting catheters into tumors for the purpose of applying therapeutic irradiation and hyperthermia are in widespread use. Several miniature microwave antenna designs are currently used for these treatments. These include multisection, hot-tip, 2- and 3-node, dipole and helical antennas, all of which are commercially available. The antenna designs are diverse enough to have a dramatic effect on the power deposition patterns either as single antennas or when used in arrays. Aside from the dipole antenna, most of the antennas have never been evaluated experimentally or theoretically in arrays, although the array configuration is used in the vast majority of all clinical treatments. Power deposition or SAR (specific absorption rate) tests were run in muscle equivalent phantom. Single antennas were evaluated at 400 points in a plane and isoSAR contours drawn, normalized to maximum SAR. Single antennas were also compared in large and small diameter catheters to evaluate catheter dependent antenna performance. The dipole, multisection, hot-tip and helical antennas were evaluated in arrays of four antennas located at the corners of a square, spaced 2.0 cm apart. Arrays of antennas were evaluated at 441 points in three planes orthogonal to the antenna axes. Results in the single antenna studies showed that the dipole was less affected by snugness of catheter fit than the multisection, hot-tip or helical antennas. In large catheters, the latter three antennas showed more extreme tip heating performance. The 2- and 3-node antennas deposited only 20% SAR in the distal 30 mm of antenna length. In arrays, the multisection, hot-tip, and dipole antennas all yielded 80-90% SAR centrally in the central measurement plane. Comparing the three antennas, the dipole array deposited 20% more power centrally in a plane near the insertion point, and the multisection and hot-tip antenna designs deposited 10% more central power in a plane near the antenna tips. The helical antenna array deposited only 30% SAR centrally in the plane near the antenna tips and in the central plane. Only 10% SAR was measured centrally near the insertion point, as expected for tip-heating antennas. Finally, the clinical significance of the results is discussed as applied to human tumors undergoing hyperthermia treatments.

Evaluation Studies as Topic

Absorbed power deposition for various insertion depths for 915 MHz interstitial dipole antenna arrays: experiment versus theory.

Dipole antennas are commonly used in interstitial clinical hyperthermia treatments because of their compatibility with brachytherapy techniques and their good power deposition patterns when used in arrays. For accurate treatment planning, however, there must be a comprehensive knowledge base to predict the power deposition patterns when insertion depth is a non-resonant length. This is especially true for insertion depths that result in significant power deposition outside of the antenna junction plane and presumably outside of the tumor volume. A computer controlled measurement system was used with a muscle equivalent phantom to make measurements of specific absorption rate (SAR) or absorbed power per unit mass of tissue at 598 points in a plane. The diagonal plane was the measurement plane of choice because it characterized the SAR profiles at the array center as well as areas in the proximity of the antennas. Dartmouth dipole antennas were used (0.9 mm O.D.) in brachytherapy catheters with inner catheters (2.2 mm O.D./1.2 mm I.D.). The resonant half-wavelength of this dipole antenna/catheter combination is 7.8 cm. A choke modification of the dipole was also investigated. Four antennas were used in a boxlike configuration with 2.0 cm separation. Insertion depths of 5.9, 7.8, 9.8, 12.7, 15.6 and 17.6 cm were used. The hA subsection (junction to tip) was held constant at 3.9 cm. Plots were made of the experimental SAR data normalized to the maximum SAR measured in the plane. Theoretical plots were calculated in the same plane for each of the insertion depths. SAR comparisons were also made longitudinally along the central axis of the array and through the antenna junctions in the diagonal plane for resonant half-wavelength insertion depth. Experimental results verified theoretical predictions of the existence of a secondary hot-spot in the center of the array, but outside of the antenna junction plane and approximately a quarter-wavelength from the insertion point. This secondary hot-spot appears for all insertion depths greater than 10 cm. At longer insertion depths approaching a full wavelength, however, this secondary peak is not dominant. Choke antennas demonstrated a solution to the problem of shifting SAR patterns with varying insertion depths by restricting the active length of the antenna.

Absorption

Design and performance of a high speed driver circuit for PIN diode switches used in microwave hyperthermia.

In many cancer treatment facilities where hyperthermia treatments are performed, there is a need to split a single channel microwave source into multiple, individually controllable channels. In the application reported here, microwave power is alternately switched between active and passive elements for each channel. The active element is either a microwave antenna inside a catheter in tumour tissue or a planar spiral applicator placed superficially, the total power to each channel being pulse width modulated from 1 to 99% of a 1 s duty cycle. The system is computer controlled and is capable of dividing and controlling power to 12 channels. PIN diode switch assemblies control the flow of power in each channel but they must be switched within a few microseconds to avoid failure at the high power levels used in the clinic. A high speed circuit was fabricated and tested to drive each PIN diode switch; the PIN diode switches are turned on in 1.5 microseconds and off in 3.0 microseconds, which meets the specifications for hot switching. The increase in speed over the former driver system is a factor of 5.1 for the on cycle and 1.5 x 10(5) for the off cycle and the maximum power tested in each channel was 80 W for 1 h at random duty cycles between 1 and 99%. The circuit was also tested with 40 W of power at duty cycles of 1, 50 and 99% for 1 h each; no failures or performance decrements were observed. The 12 channel circuit driver has been used for six months of clinical treatments without failure.

Equipment Design

Thermal conduction effects associated with temperature measurements in proximity to radiofrequency electrodes and microwave antennas.

The smearing effects due to thermal conduction along various, nonenergized, interstitial devices were quantified in a flow cell-thermal step gradient. An insulated cylindrical flow cell with a high (ca 45 degrees C, 1.12 cm i.d., 1.6 cm o.d.) temperature region surrounded by a low (ca 37 degrees C) temperature region was used to compare temperature profiles measured with a thermocouple sensor inside a Stanford radiofrequency (RF) hyperthermia/brachytherapy catheter, a BSD instrumented microwave (MW) antenna (i.e., thermistor integrated into a dipole antenna) and a Dartmouth MW antenna with a juxtaposed optical sensor. Two parameters were used to quantify the thermal smearing of each interstitial device in the flow cell: (a) the maximum temperature difference (MTD) and (b) the full- width- half-maximum (FWHM) of the high temperature region. The "true" temperature maximum (45.4 degrees C) and distribution (FWHM = 1.65 +/- 0.06 cm) were measured with an optical sensor. These data indicate that the BSD instrumented MW antenna significantly smeared the true temperature profile (MTD = 2.7 degrees C, FWHM = 2.1 cm), as did the Dartmouth MW antenna (MTD = 1.5 degrees C, FWHM = 1.7 cm). The Stanford RF catheter, when insulated, resulted in minimal smearing (MTD = 0.3 degrees C, FWHM = 1.9 cm). Moreover, when the insulation was removed so the RF electrode was exposed to the thermal step gradient, smearing was again minimal (MTD = 0.3 degrees C, FWHM = 1.9 cm).

Brachytherapy