Biomedical subjects

T P Ryan

Publications and source records attributed to T P Ryan.

At least 37 records · Page 2Linked to original sources

PubMed1992

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↗

PubMed1992

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↗

PubMed1992

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↗

PubMed1991

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↗

PubMed1991

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↗

PubMed1991

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↗

PubMed1990

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↗

PubMed1989

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↗

PubMed1989

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↗

PubMed1987

Iridium-192 brachytherapy in combination with interstitial microwave-induced hyperthermia for malignant glioma.

A phase I clinical trial assessing the feasibility and safety of hyperthermia in combination with 192Ir brachytherapy (60 Gy) for the treatment of malignant glioma now includes 14 patients. Hyperthermia (42-43 degrees C at tumor margin for 60 min) has been induced using stereotactically implanted afterloading catheters and a microwave (915 or 2,450 MHz) antenna array. Thermometry recorded along each catheter confirms the general ability of the technique to heat such volumes, but thermal heterogeneities are documented. Transient or permanent worsening of previous neurologic deficit, seen in 7 patients, has been the most common morbidity.

Adult↗

PubMed1986

Use of a flexible epidural stimulating electrode for intraoperative monitoring of spinal somatosensory evoked potentials.

The use of an epidural stimulating spinal electrode has been adapted for recording spinal somatosensory evoked potentials (SSEP) during spinal surgery. This technique utilizes a flexible, 1 mm diameter electrode with four platinum contacts that is easily slipped into the epidural space both rostral and caudal to the exposed surgical field. The flexibility of the electrode assembly ensures against dural penetration. Incoming somatosensory spinal evoked potentials recorded using the lumbosacral electrode are compared with the SSEP recorded above the surgical site (rostral electrode). The spinal SEPs were generally triphasic (thoracic) or polyphasic (lumbosacral) with an amplitude of 5 microV. This system has been used for intraoperative monitoring during 33 major spinal operations. Waveform morphology, as well as the latencies and amplitudes of the component peaks of the spinal SEPs remained relatively constant compared with the cortical SEPs.

Electric Stimulation↗

PubMed1986

Spinal and cortical somatosensory evoked potential monitoring during corrective spinal surgery with 108 patients.

To reduce the incidence of neurologic complications following spinal surgery, somatosensory evoked potentials (SEPs) were monitored in 108 patients. An electrode with four in-line contacts was used to record spinal SEPs in the epidural space in 33 patients at locations both rostral and caudal to the surgical site. Cortical SEPs were successfully monitored in 107/108 patients and spinal SEPs in all 33 attempted epidurally. Spinal conduction velocities were found to range from 43.9 to 110.5 m/s depending on vertebral level and the time location of the measured peak in the response waveform. Frequency power spectra of the SEP waveforms were found to be a reliable adjunct to peak latency amplitude analysis in the time domain. Use of caudal and rostral epidural, subcortical, and cortical electrode sites were found to be the most reliable technique for the maximum patient safety.

Adolescent↗

PubMed1985

Digital heart rate monitor derived from the arterial pressure pulse.

This monitor displays heart rate without the need for electrical contact with the experimental animal. The device uses a quartz pressure transducer connected to an arterial catheter and has a full scale accuracy of +/- 3 beats min-1; its range is 0-400 beats min-1. There is an output voltage proportional to heart rate and internal calibration facilities are provided at 60 and 360 beats min-1.

Animals↗

PubMed1984

Computer-controlled temperature multiplexer for thermal dosimetry studies.

Thermistor probes are widely used for mapping thermal distributions in hyperthermia research. To facilitate multi-probe mapping, a computer-controlled multiplexer for automated thermistor impedance measurement and temperature conversion is described. A complete hardware interface schematic is shown. An algorithm which calculates individual temperature values as a function of thermistor impedance is tested. Total error is quantified by calculating the absolute error between the theoretical temperatures obtained from the algorithm and the experimental calibration temperatures obtained from a National Bureau of Standards referenced mercury thermometer. If calibration intervals of 1.00 degree C or less are used, the total error of the system is less than 0.10 degree C.

Biomedical Engineering↗

PubMed1981

A possible role in transcription for the single-stranded DNA binding protein of bacteriophage T7.

A spontaneous rifampicin-resistant mutant of E. coli, RpoB26, which inhibits the growth of bacteriophage T7, has been described in the accompanying paper (Schwarz et al.). The rifr mutation appears to increase the rate of transcriptional termination in a rho-deficient strain. T7 mutants with the ability to grow (Gor+) on the Rifr mutant were isolated, and some of their properties were investigated. One of these Gor+ mutants has a small deletion, located between nucleotides 9694 and 9820 of the T7 DNA sequence (Dunn and Studier 1980), which affects the size of the T7 single-stranded DNA binding protein (ssDBP), the product of gene 2.5 (p 2.5) (Dunn and Studier 1980). The Gor+ phenotype was also mapped to this region by genetic methods. Gor+ is recessive to the wild-type (Gor-) phenotype. This suggests that the T7 ssDBP may normally increase the frequency of transcriptional termination in the early region by binding to single-stranded nucleic acid configurations, and so affecting molecular conformations involved in the termination process. Excessive termination in RpoB26 could therefore be compensated for by alterations of the ssDBP.

Carrier Proteins↗

PubMedDate not supplied

Determination of self-absorption corrections for gamma analysis of environmental samples: comparing gamma-absorption curves and spiked matrix-matched samples.

Accurate determination of the massic activity of gamma-emitting radionuclides in environmental samples, particularly sediments and soils, cannot be achieved without taking into account sample self-absorption. The extent of self-absorption in the sample will depend on a number of factors including sample composition, density, sample size and gamma-ray energy. The preferred method for correcting for this effect is to use spiked or natural matrix reference materials that match each sample type to be analysed. However, for laboratories that must measure a wide variety of sample matrices this method is too costly and time-consuming. Another technique commonly used is to make direct gamma-ray transmission measurements for each sample. This method, while more practical, still requires a minimum of three measurements to be made for each sample analysed. A more convenient method is to prepare sets of gamma-absorption curves. This approach involves making a series of direct transmission measurements for samples of varying densities but similar type. Sets of matching samples, both spiked and unspiked, were prepared and density correction factors determined using the direct transmission method and the spiked sample approach. It was found that, for soil and sediment samples, these two methods typically differed by 5-9% for higher energy gamma rays and by 12-15% for the 59.54 keV 241Am peak. Gamma-absorption curves were also derived and, for the admittedly limited dataset, 95% confidence intervals of +/-7% for the curve generated using the spiked samples method were obtained.

Calibration↗

PubMedDate not supplied

Transluminal radiofrequency tissue ablation with use of metallic stents.

PURPOSE: To determine if transluminal coagulative necrosis can be induced by applying radiofrequency (RF) energy to indwelling metallic stents. MATERIALS AND METHODS: RF energy was applied to metallic alloy stents (20-68 mm length, 5-16 mm diameter) in tissue phantom (n = 31), ex vivo bovine liver (n = 10), and in vivo porcine hepatic veins (n = 4). For ex vivo and in vivo liver experiments, RF was applied for 5-6 minutes, titrating generator output to produce 85 degrees-95 degrees C temperatures at the stent surface. Local and remote temperature sensing was performed. Imaging and pathologic studies documented the extent of coagulation necrosis. RESULTS: Phantom studies demonstrated uniform temperature distribution along the entire stent length for all Elgiloy stents powered for 2 minutes with a minimum of 120 watts. Shorter stents required less power or reduced time to achieve uniform temperature. In ex vivo liver, 25-mm stents (n = 5) showed 8-10 mm of uniform circumferential coagulation necrosis along the entire stent length. Fifty-millimeter stents showed less uniform coagulation necrosis. For the in vivo stents (20 mm), 8-10 mm of uniform circumferential coagulation necrosis surrounded the stent along its entire length. CONCLUSION: Metallic stents can be used to deliver transluminal RF energy from an external source, inducing heat deposition with resultant circumferential tissue coagulation. Clinical applications might include reduction of intimal proliferation in vascular diseases and/or treatment of periluminal tumors compressing the bile ducts, the urethra, or other luminal structures.

Animals↗

PubMedDate not supplied

Effects of (+)-1,2-bis(3,5-dioxopiperazin-1-yl)propane (ADR-529) on iron-catalyzed lipid peroxidation.

ADR-529 [(+)-1,2-bis(3,5-dioxopiperazin-1-yl)propane], a nonpolar, cyclic analogue of EDTA, protects against anthracycline cardiotoxicity in vivo. The protective mechanism presumably involves chelation of iron by a hydrolysis product of ADR-529, thus preventing the formation of reactive iron/oxygen species which can damage membrane lipids. We investigated the effects of ADR-529 and its hydrolysis products (the tetraacid and the diacid diamide) on NADPH- and ADP-Fe(3+)-dependent lipid peroxidation of rat liver microsomes and liposomes in the presence of cytochrome P-450 reductase. Hydrolyzed ADR-529 products caused inhibition of lipid peroxidation when in excess of the iron concentration. However, no inhibition of lipid peroxidation was detected by similar concentrations of nonhydrolyzed ADR-529. Microsomes did not affect the inhibition of lipid peroxidation, suggesting that rat liver microsomes do not hydrolyze ADR-529. Similarly, the diacid diamide hydrolysis product of ADR-529 inhibited ferritin- and adriamycin-iron-dependent liposomal lipid peroxidation in a concentration-dependent manner. No correlation between partially reduced oxygen species (O2.- and .OH; as measured by electron spin resonance) and lipid peroxidation (as assayed by malondialdehyde formation) was observed, suggesting that liposomal lipid peroxidation was strictly an iron-dependent phenomenon. These results suggest that inhibition of lipid peroxidation by iron chelation may be related to the protective effects of ADR-529 on in vivo anthracycline toxicity.

Animals↗