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Biomedical subjects

T C Cetas

Publications and source records attributed to T C Cetas.

52 records · Page 3Linked to original sources

Will hyperthermia conquer the elusive hypoxic cell? Implications of heat effects on tumor and normal-tissue microcirculation.

In tumor radiobiology, the hypoxic cell has become especially important because of recent evidence of acute hypoxic regions within experimental tumors. The impact of hyperthermia on the development of acute hypoxia is discussed. Two experiments for studying hyperthermia and hypoxia in tumors are presented. Knowledge of the microenvironment of tumor cells will be necessary to understand and improve tumor control.

Adult↗

Therapeutic synergism of hyperthermia-cis-platinum in a mouse tumor model.

A small-animal model was developed as a guide to whole-body hyperthermia in cancer patiens. Anesthetized DBA/2 mice were secured to a platform, and their hindlimbs were immersed in a 42.3 degrees C water bath for 30-60 minutes. Hindlimb hyperthermia reulted in steady-state rectal and femoral bone marrow and muscle temperatures of 42 degrees C and upper extremity muscle and esophagus temperatures of 41 degrees C. With this hyper thermia technique, the mouse spleen colony assay could be used to quantitate the lethality of hyperthermia and/or cis-dichloro-diammineplatinum(II) (cis-platinum) on clonogenic bone marrow and leukemia cells. Hyperthermia prior to cis-platinum administration increased cis-platinum inhibition of leukemia colony formation as much as 2 logs; however, antileukemia synergism ws greatest when cis-platinum administration immediately preceded hyperthermia and no evidence existd of synergism against normal bone marrow colonies. Correlative in vivo drug uptake studies showed a marked increase in leukemia cell uptake of 195mPt-cis-platinum at elevated temperatures, which suggested a potential mechanism for the apparent antileukemia synergism of cis-platinum and heat.

Animals↗

Theoretical comparison of the SAR distributions from arrays of modified current sheet applicators with that of lucite cone applicators using Gaussian beam modelling.

The technical comparison of Current Sheet Applicator (CSA) and Lucite Cone Applicator (LCA) arrays covering an area of approximately 20 x 20 cm2 is investigated based on Gaussian beam (GB) predicted SAR distributions. The comparison is made in muscle equivalent tissue at 1 cm depth (maximum SAR normalized to 100%) and over a volume of 3 cm depth under the aperture of the antennae. The planar SAR distribution is tested on field sizes (FSx: area covering x% SAR), penetration depth (PD) and homogeneity coefficient (HC = FS75/FS25). From the SAR volume, a SAR-Volume histogram (volume enclosing y% SAR/total volume) is calculated as well as the volumetric HC. First, the prototype CSA (aperture 58 x 67 mm2, FS50 = 21 cm2) is technically modified to assure clinical safety and load independence. The modified CSA, the D-CSA, has an aperture of 66 x 75 mm2 with an FS50 = 28 cm2 and a PD of 10 mm, the LCA (aperture 105 x 105 mm2) has an FS50 = 76 cm2 and PD = 12 mm. The HC equals 0.21 (D-CSA), respectively 0.22 (LCA). Secondly, a 3 x 3 D-CSA array is compared with a 2 x 2 LCA array. The FS50s equals 72% (D-CSA), respectively 75% (LCA). The SAR-volume histograms, planar and volumetric HC show no significant difference; however, the planar HCs for D-CSA and LCA increase from 0.2-0.3, indicating that incoherently powered arrays from these antennae build SAR distributions constructively.

Algorithms↗

Thermometry considerations in localized hyperthermia.

The introduction of local hyperthermia as a method of cancer therapy implies the necessity of quantitative measurements of the thermal dose. Our intention is to describe the nature of the problem, both physically and physiologically, with illustrations drawn from thermographic measurements in phantoms and in animals. The characteristics of a thermometry calibration facility are described. Some measurement problems associated with conventional thermometer probes are mentioned and several new thermometers which were developed for use in the electromagnetic fields are reviewed. We present some of the concepts that will guide the development of noninvasive thermometry. Systemic hyperthermia is not considered. We recommend that other reviews specifically directed toward localized hyperthermia be prepared on the methods of heating and on thermal physiological problems.

Adenoma↗

Three-dimensional simulations of ferromagnetic implant hyperthermia.

A general three-dimensional planning program has been developed for hyperthermia treatments for cancer. In this study, the program is used to analyze the three-dimensional temperature distributions generated by interstitial ferromagnetic implants. An empirical power absorption formula developed by Haider for thermally self-regulating nickel-silicon ferromagnetic seeds has been used to calculate the seed power absorption as a function of seed temperature. By properly choosing the seed type (Curie point of seeds), and by using appropriate seed spacing, this heating modality can generate desirable three-dimensional temperature distributions for many different situations over a fairly large range of blood perfusion values. Detailed information regarding the choice of the Curie points of the seeds and the seed spacing for certain blood perfusions is also given as a quantitative guide for treatment planning.

Computer Simulation↗

Estimation of complete temperature fields from measured transient temperatures.

In hyperthermia treatments, it is desirable to be able to predict complete tissue temperature fields from the limited number of sampled temperatures available. Because of the unknown tissue blood perfusion this is a particularly difficult problem, whose eventual solution will require a considerable effort. An initial attempt to develop methods to solve this problem automatically using unconstrained optimization techniques (which minimize the differences between measured steady-state temperatures and the temperatures predicted from treatment simulations) has been reported previously. A second technique using transient temperatures following a step decrease in power has been developed and is presented and discussed in this paper. The results of applying both it and the steady-state technique to simulated hyperthermia treatments are compared for one-dimensional situations. This transient technique predicts complete temperature fields more accurately and robustly than the steady-state approach. In particular, it can better predict the complete temperature fields in situations where the number of unknown blood perfusion parameters is greater than the number of available temperature sensors.

Chemotherapy, Cancer, Regional Perfusion↗

Regional hyperthermia for deep-seated malignancies using the BSD annular array.

Forty-four patients were treated using the BSD-1000 Annular Phased Array between April 1983 and December 1986. There were 32 pelvic, nine abdominal, two extremity, and one thoracic sites treated. Mean tumour volume was 646 cc. Thirty-nine patients had concurrent radiation therapy, receiving a mean dose of 38 Gy. Mean average temperature was 41.0 +/- 1.4 degrees C. Most patients experienced local or systemic toxicity, requiring temporary treatment interruption in 33 patients, and termination of treatment in eight. Chronic complications were seen in four, but these were in patients receiving high total radiation doses as well. There were six complete and five partial responses. Among the 32 patients with pelvic tumours, mean tumour volume was 317 cc, mean radiation dose was 42 Gy, and mean average temperature was 41.3 +/- 1.2 degrees C. There were five complete and four partial responses. Achieving tumour temperatures greater than or equal to 42 degrees C with the annular array is difficult, due to both systemic and local toxicity. To improve clinical hyperthermia for thoracic, abdominal, and pelvic tumours, new technologies such as steerable phased array microwave systems; scanned, focused ultrasound; and permanently implantable thermoregulating ferromagnetic seeds, or new approaches such as using drugs to alter blood flow, or combining hyperthermia with antineoplastic drugs or biological agents, will be necessary.

Clinical Trials as Topic↗

Clinical evaluation of hyperthermia equipment: the University of Arizona Institutional Report for the NCI Hyperthermia Equipment Evaluation Contract.

Two-hundred and fifteen independent sites in 203 patients were treated with hyperthermia at the University of Arizona from 10/81 through 3/86 under the auspices of this contract. In the head and neck, a site dominated by superficial tumors, air-coupled and water-coupled microwave applicators yielded the best results. Similarly in the thorax, also dominated by superficial tumors, water-coupled microwave applicators were best. In the abdomen and pelvis, sites dominated by deep tumors, only interstitial radiofrequency (RF) heating, an invasive technique useful only in selected cases, was capable of consistently producing therapeutic temperatures. Toxicity appeared to be site-related, and treatment discomfort was especially common in abdominal and pelvic sites. In conclusion, while superficial sites were readily heated using propagative electromagnetic devices, these devices were ineffective and poorly tolerated at deeper sites. Effective deep hyperthermia was best produced with interstitial techniques, and further development of these techniques using RF electrodes, implantable microwave antennas and thermoregulating ferromagnetic seeds, as well as scanned, focussed-ultrasound techniques, holds promise for effective heating of deep visceral sites.

Clinical Trials as Topic↗

Errors between two- and three-dimensional thermal model predictions of hyperthermia treatments.

A simulation program to study the three-dimensional temperature distributions produced by hyperthermia in anatomically realistic inhomogenous tissue models has been developed using the bioheat transfer equation. The anatomical data for the inhomogeneous tissues of the human body are entered on a digitizing tablet from serial computed tomography (CT) scans. Power deposition patterns from various heating modalities must be calculated independently. The program has been used to comparatively evaluate two- and three-dimensional simulations in a series of parametric calculations based on a simple inhomogeneous tissue model for uniform power deposition. The conclusions are that two-dimensional simulations always lead to significant errors at the ends of tumors (up to tens of degrees). However, they can give valid results for the central region of large tumors, but only with tumor blood perfusions greater than approximately 1 kg/m3/s. These conclusions from the geometrically simple model are substantiated by the results obtained using the full three-dimensional model for actual patient anatomical simulations. In summary, three-dimensional simulations will be necessary for accurate patient treatment planning. The effect of the thermal conductivity, used in the models, on the temperature field has also been studied. The results show that using any thermal conductivity value in the range of 0.4 to 0.6 W/m/degrees C sufficiently characterizes most soft tissues, especially in the presence of high blood perfusion. However, bone (thermal conductivity of 1.16 W/m/degrees C) and fat (thermal conductivity of 0.2 W/m/degrees C) do not fit this generalization and significant errors result if soft tissue values are used.

Blood Circulation↗

Experimental assessment of phased-array heating of neck tumours.

An investigation of phased-array microwave systems (PAMS) for non-invasively inducing hyperthermia, primarily in neck lesions, has been done with implications for applications at other sites such as lung and pelvis. Our general approach was to combine numerical and analytical approaches with parallel experimental studies. In this paper we will concentrate only on the experimental aspects. The object, such as a homogeneous cylindrical phantom or a neck phantom, was encircled with several standard applicators driven by a single source, but with relative phase and amplitude control over each applicator. The relative phases of the applicators were adjusted by using an implanted monopole antenna connected to an HP network analyser. Power was applied and the specific absorption rate (SAR) was determined by using split phantoms and thermography or by measuring temperature transients dT/dt, recorded by implanted thermometer probes. We found that at 915 MHz for our applicators (SMA Co.) the centre of an 11 cm diameter muscle-like phantom heated to about 33% of the value at the surface in front of the applicator. Similarly, we were able to show significant SAR at the centre of realistically sized neck phantoms using four phased apertures of 915 MHz. Furthermore, substantial improvement was observed if the frequency was lowered to about 400 MHz.

Animals↗

Heating pattern of helical microwave intracavitary oesophageal applicator.

Helical microwave intracavitary oesophageal (HMIO) applicators were designed to operate at frequencies of 433 MHz and 915 MHz. Heating patterns were studied within muscle-equivalent phantom by thermographic camera and fibreoptic thermometers. The results showed that frequency significantly influenced the microwave heating pattern. The 433 MHz applicator had a single power deposition region, the longitudinal specific absorption rate (SAR) distribution appeared to be nearly even, and the maximum SAR value occurred close to the centre of the active length of the applicator. The 915 MHz applicator had two power deposition regions, the peak SAR values occurred at about 1/4 and 3/4 of the active length respectively. The radial SAR distribution suggested that there is no obvious difference between the 433 MHz and 915 MHz applicators in that the average radial penetration of 50% surface SAR (RP50) was about 0.65 cm. It was also shown that power deposition was axially symmetric for both 433 MHz and 915 MHz HMIO applicators. It is shown that better impedance matching is more important for intracavitary hyperthermia than for external hyperthermia. Choosing HMIO applicators in clinical practice is also discussed.

Esophageal Neoplasms↗

Errors in the two-dimensional simulation of ferromagnetic implant hyperthermia.

An empirical power absorption formula developed by Haider et al. (1991) for thermally self-regulating nickel-silicon ferromagnetic seeds has been incorporated into a three-dimensional patient treatment planning programme to calculate the seed power absorption as a function of seed temperature. The programme has been used to evaluate systematically the accuracy of two- versus three-dimensional simulations for ferromagnetic implant hyperthermia. The results show that two-dimensional simulations can significantly overestimate temperatures. Consequently, three-dimensional simulations are necessary for accurate hyperthermia treatment planning.

Computer Simulation↗

Current sheet applicator arrays for superficial hyperthermia of chestwall lesions.

The current sheet applicator is an electromagnetic heating device whose size may be chosen virtually independent of frequency even though practical limitations may restrict it to VHF and UHF bands. In this paper we investigate absorbed power distributions in muscle tissue from current sheet applicators when used as elements of a planar array intended for superficial hyperthermic treatment of tumours. Advantages offered by current sheet applicators for tissue heating include compact size, a linear polarization of the induced electric field and relatively large heating area. It is shown that the effective field produced by a pair of these elements is continuous regardless of whether the common edges of the elements are perpendicular or parallel to the direction of impressed current. The feasibility of customizing the shape and size of the field is also illustrated. The absorbed power distribution patterns due to a coherently driven array operating around 434 MHz is relatively insensitive to phase variations of about 20 degrees but is sensitive to relative power level variations as low as 10%. Mutual coupling between array elements may be reduced to acceptable levels by incorporating suitable spacing between them. It is also demonstrated that there is good agreement between measurements of absorbed power distributions and predictions using the Gaussian beam model.

Biomedical Engineering↗

Miniature dipole E-field probes for characterizing both phase and amplitude of microwave radiators for hyperthermia.

This paper describes a system for characterizing th electric field patterns of microwave radiators in lossy media, in particular, of those used in hyperthermia treatments for cancer therapy. We discuss the design, fabrication and testing of small, minimally-perturbing electric field probes which are capable of measuring both amplitude and phase. An appropriate test configuration for mapping field patterns radiating from hyperthermia applicators (antennae) also is described. The system was developed specifically for the evaluation of applicators centered at 434 MHz and 915 MHz.

Electronics, Medical↗