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S T Clegg

Publications and source records attributed to S T Clegg.

At least 19 recordsLinked to original sources
PubMed2000

Perturbations in hyperthermia temperature distributions associated with counter-current flow: numerical simulations and empirical verification.

Two numerical techniques are used to calculate the effect of large vessel counter-current flow on hyperthermic temperature distributions. One is based on the Navier-Stokes equation for steady-state flow, and the second employs a convective-type boundary condition at the interface of the vessel walls. Steady-state temperature fields were calculated for two energy absorption rate distributions (ARD) in a cylindrical tissue model having two pairs of counter-current vessels (one pair with equal diameter vessels and another pair with unequal diameters). The first assumed a uniform ARD throughout cylinder; the second ARD was calculated for a tissue cylinder inside an existing four antenna Radiofrequency (RF) array. A tissue equivalent phantom was constructed to verify the numerical calculations. Temperatures induced with the RF array were measured using a noninvasive magnetic resonance imaging technique based on the chemical shift of water. Temperatures calculated using the two numerical techniques are in good agreement with the measured data. The results show: 1) the convective-type boundary condition technique reduces computation time by a factor of ten when compared to the fully conjugated method with little quantitative difference (approximately 0.3 degree C) in the numerical accuracy and 2) the use of noninvasive magnetic resonance imaging (thermal imaging) to quantitatively access the temperature perturbations near large vessels is feasible using the chemical shift technique.

Body Temperature Regulation↗
PubMed1999

Dynamic contrast-enhanced MRI and fractal characteristics of percolation clusters in two-dimensional tumor blood perfusion.

Dynamic contrast-enhanced magnetic resonance imaging (DE-MRI) of the tumor blood pool is used to study tumor tissue perfusion. The results are then analyzed using percolation models. Percolation cluster geometry is depicted using the wash-in component of MRI contrast signal intensity. Fractal characteristics are determined for each two-dimensional cluster. The invasion percolation model is used to describe the evolution of the tumor perfusion front. Although tumor perfusion can be depicted rigorously only in three dimensions, two-dimensional cases are used to validate the methodology. It is concluded that the blood perfusion in a two-dimensional tumor vessel network has a fractal structure and that the evolution of the perfusion front can be characterized using invasion percolation. For all the cases studied, the front starts to grow from the periphery of the tumor (where the feeding vessel was assumed to lie) and continues to grow toward the center of the tumor, accounting for the well-documented perfused periphery and necrotic core of the tumor tissue.

Animals↗
PubMed1999

Computational techniques for fast hyperthermia temperature optimization.

Hyperthermia temperature optimization involves arriving at a temperature distribution which minimizes a stated goal function, the goal function having a biological basis in maximizing tumor cell kill while not exceeding normal tissue toxicity. This involves the computationally intensive process of multiple evaluations of the temperature goal function, requiring repeated evaluations of the power deposition and its corresponding temperature distribution. Two computational schemes are proposed to expedite the temperature optimization process: (1) temperature distribution evaluation by superpositioning precomputed distributions, and (2) using representative tissue groups (rather than every point in the domain) to evaluate the goal function. The application of these schemes is illustrated with a typical optimization problem, as applied to symmetric and asymmetric, heterogeneous models. Application of these schemes reduced the optimization time on a DEC Alpha 1000 4/266 (Alpha is a registered trademark of Digital Equipment Corporation.) from several h to min, with little difference in results. The computational schemes, though demonstrated in the context of electromagnetic hyperthermia, are generally applicable to other forms of nonionizing radiation employed in hyperthermia therapy.

Humans↗
PubMed1998

Magnetic resonance thermometry during hyperthermia for human high-grade sarcoma.

PURPOSE: To determine the feasibility of measuring temperature noninvasively with magnetic resonance imaging during hyperthermia treatment of human tumors. METHODS: The proton chemical shift detected using phase-difference magnetic resonance imaging (MRI) was used to measure temperature in phantoms and human tumors during treatment with hyperthermia. Four adult patients having high-grade primary sarcoma tumors of the lower leg received 5 hyperthermia treatments in the MR scanner using an MRI-compatible radiofrequency heating applicator. Prior to each treatment, an average of 3 fiberoptic temperature probes were invasively placed into the tumor (or phantom). Hyperthermia was applied concurrent with MR thermometry. Following completion of the treatment, regions of interest (ROI) were defined on MR phase images at each temperature probe location, in bone marrow, and in gel standards placed outside the heated region. The median phase difference (compared to pretreatment baseline images) was calculated for each ROI. This phase difference was corrected for phase drift observed in standards and bone marrow. The observed phase difference, with and without corrections, was correlated with the fiberoptic temperature measurements. RESULTS: The phase difference observed with MRI was found to correlate with temperature. Phantom measurements demonstrated a linear regression coefficient of 4.70 degrees phase difference per degree Celsius, with an R2 = 0.998. After human images with artifact were excluded, the linear regression demonstrated a correlation coefficient of 5.5 degrees phase difference per degree Celsius, with an R2 = 0.84. In both phantom and human treatments, temperature measured via corrected phase difference closely tracked measurements obtained with fiberoptic probes during the hyperthermia treatments. CONCLUSIONS: Proton chemical shift imaging with current MRI and hyperthermia technology can be used to monitor and control temperature during treatment of large tumors in the distal lower extremity.

Adult↗
PubMed1994

Inverse techniques in hyperthermia: a sensitivity study.

Numerical modeling methods and hyperthermia treatment temperature measurements have been used together to reconstruct steady-state tumor temperature distributions. However, model errors will exist which may in turn produce errors in the reconstructed temperature distributions. A series of computer experiments was conducted to study the sensitivity of reconstructed two-dimensional temperature distributions to perfusion distribution modeling errors. Temperature distributions were simulated using a finite element approximation of Pennes' bioheat transfer equation. Relevant variables such as tumor shape, perfusion distribution, and power deposition were modeled. An optimization method and the temperatures "measured" from the simulated temperature distributions were used to reconstruct the tumor temperature distribution. Using this procedure, the sensitivity of the reconstructed tumor temperature distribution to model-related errors, such as the perfusion function, was studied. It was found that: 1) if the problem is conduction dominated, large errors in the perfusion distribution produce only small errors in the reconstructed temperature distribution (maximum error < 1.0 degrees C), and 2) when the actual perfusion distribution contains a small random variation (+/- 15%) which is neglected by the model, the reconstructed temperature distribution will be in good agreement with the actual temperature distribution (maximum error < or = 0.3 degrees.

Algorithms↗
PubMed1993

Sensitivity of hyperthermia trial outcomes to temperature and time: implications for thermal goals of treatment.

PURPOSE: In previous work we have found that the cumulative minutes of treatment for which 90% of measured intratumoral temperatures (T90) exceeded 39.5 degrees C was highly associated with complete response of superficial tumors. Similarly, the cumulative time for which 50% of intratumoral temperatures (T50) exceeded 41.5 degrees C was highly associated with the presence of > 80% necrosis in soft tissue sarcomas resected after radiotherapy and hyperthermia. In the present work we have calculated the time for isoeffective treatments with T90 = 43 degrees C and T50 = 43 degrees C, respectively, using published thermal isoeffective dose formulae. The purpose of these calculations was to determine the sensitivity of treatment outcome to variations in thermal isoeffective dose. METHODS AND MATERIALS: The basis for the calculations were the thermal parameters and treatment outcomes in three patient populations: 44 patients with moderate or high grade soft tissue sarcoma treated preoperatively with hyperthermia and radiation; 105 patients with superficial tumors treated with hyperthermia and radiation, and 59 patients with deep tumors treated with hyperthermia and radiation. RESULTS: The thermal dose values calculated are strongly associated with outcome in multivariate logistic regression analysis. Simple dose-response equations result from the analysis, and we use these equations to assess the sensitivity of outcome upon variations in thermal dose. This information, in turn, allows us to estimate the number of patients required in Phase II and III trials of hyperthermia and radiation therapy. CONCLUSIONS: For regimens of 5 to 10 hyperthermia treatments, improvements in median T90 (superficial tumors) and T50 (deep tumors) parameters by 1.2-1.5 degrees C could result in response rates high enough (compared to radiotherapy alone) to justify Phase III trials. A similar improvement in response rates would require an increase in overall duration of treatment by a factor of 3 to 5. This would be difficult to achieve while also avoiding thermal tolerance induction. Achieving these temperature goals may be possible with improvements in hyperthermia technology. Alternatively, there may be ways to increase the sensitivity of cells to temperatures that can be achieved currently, such as pH reduction or chemosensitization.

Combined Modality Therapy↗
PubMed1993

Reconstruction of experimental hyperthermia temperature distributions: application of state and parameter estimation.

Subsets of data from spatially sampled temperatures measured in each of nine experimental heatings of normal canine thighs were used to test the feasibility of using a state and parameter estimation (SPE) technique to predict the complete measured data set in each heating. Temperature measurements were made at between seventy-two and ninety-six stationary thermocouple locations within the thigh, and measurements from as few as thirteen of these locations were used as inputs to the estimation algorithm. The remaining (non "input") measurements were compared to the predicted temperatures for the corresponding "unmeasured" locations to judge the ability of the estimation algorithm to accurately reconstruct the complete experimental data set. The results show that the predictions of the "unmeasured" steady-state temperatures are quite accurate in general (average errors usually < 0.5 degrees C; and small variances about those averages) and that this reconstruction procedure can yield improved descriptors of the steady-state temperature distribution. The accuracy of the reconstructed temperature distribution was not strongly affected by either the number of perfusion zones or by the number of input sensors used by the algorithm. One situation extensively considered in this study modeled the thigh with twenty-seven independent regions of perfusion. For this situation, measurements from ninety-six to thirteen sensors were used as input to the estimation algorithm. The average error for all of these cases ranged from -0.55 degrees C to +0.75 degrees C, respectively, and was not strongly related to the number of sensors used as input to the estimation algorithm.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗
PubMed1992

Feasibility of estimating the temperature distribution in a tumor heated by a waveguide applicator.

The feasibility of using a 2-dimensional (2D) modeling approach for retrospectively describing complete temperature distributions in the midplane of a tumor during a clinical hyperthermia treatment was tested. An experimental treatment, using a 915-MHz waveguide applicator to heat a large melanoma in a dog, was modeled. Detailed measurements of temperatures were made during the treatment. The steady-state blood flow distribution at the midplane was imaged by positron emission tomography (PET), and these data were used to prescribe the modeled perfusion pattern. A 2D finite element method (FEM) was used to approximate the solution to Maxwell's Equations to obtain the specific absorption rate (SAR) distribution. The blood-flow estimates, assumed material properties, SAR distribution, and temperature boundary conditions were then used with the same mesh in a second FEM program to obtain a solution to the bioheat transfer equation. This latter routine was embedded in a state-and-parameter-estimation program that systematically varied selected parameters until the differences between computed and measured temperatures were minimized. Optimizations were performed independently for three subsets of the measured temperature data to assess the sensitivity of the predicted temperature field to the number of measurements. The calculated temperature distributions that resulted were similar to each other, and the predicted temperatures at the sensor points excluded from these optimizations were in reasonable agreement with the measurements. However, lack of unique blood flow values following optimization indicates that the methods of estimating blood flow will need to be improved or that there are problems with model mismatch. This work is a clinical case study of an evolving 2D system of thermal dosimetry which relies on both empirical and theoretical concepts. The methodology is being evaluated for its ability to generate prognostically significant descriptors of the treatment temperature field.

Animals↗
PubMed1991

Estimating three-dimensional temperature fields during hyperthermia: studies of the optimal regularization parameter and time sampling period.

During hyperthermia therapy it is desirable to know the entire temperature field in the treatment region. However, accurately inferring this field from the limited number of temperature measurements available is very difficult, and thus state and parameter estimation methods have been used to attempt to solve this inherently ill-posed problem. To compensate for this ill-posedness and to improve the accuracy of this method, Tikhonov regularization of order zero has been used to significantly improve the results of the estimation procedure. It is also shown that the accuracies of the temperature estimates depend upon the value of the regularization parameter, which has an optimal value that is dependent on the perfusion pattern and magnitude. In addition, the transient power-off time sampling period (i.e., the length of time over which transient data is collected and used) influences the accuracy of the estimates, and an optimal sampling period is shown to exist. The effects of additive measurement noise are also investigated, as are the effects of the initial guess of the perfusion values, and the effects of both symmetric and asymmetric blood perfusion patterns. Random perfusion patterns with noisy data are the most difficult cases to evaluate. The cases studied are not a comprehensive set, but continue to show the feasibility of using state and parameter estimation methods to reconstruct the entire temperature field.

Algorithms↗
PubMed1985

A comparative evaluation of unconstrained optimization methods applied to the thermal tomography problem.

In cancer hyperthermia treatments, it is important to be able to predict complete tissue temperature fields from sampled temperatures taken at the limited number of locations allowed by clinical constraints. An initial attempt to do this automatically using unconstrained optimization techniques to minimize the differences between experimental temperatures and temperatures predicted from treatment simulations has been previously reported [1]. This paper reports on a comparative study which applies a range of different optimization techniques (relaxation, steepest descent, conjugate gradient, Gauss, Box-Kanemasu, and Modified Box-Kanemasu) to this problem. The results show that the Gauss method converges more rapidly than the others, and that it converges to the correct solution regardless of the initial guess for the unknown blood perfusion vector. A sensitivity study of the error space is also performed, and the relationships between the error space characteristics and the comparative speeds of the optimization techniques are discussed.

Hot Temperature↗
PubMedDate not supplied

Experimental evaluation of the thermal properties of two tissue equivalent phantom materials.

Tissue equivalent radio frequency (RF) phantoms provide a means for measuring the power deposition of various hyperthermia therapy applicators. Temperature measurements made in phantoms are used to verify the accuracy of various numerical approaches for computing the power and/or temperature distributions. For the numerical simulations to be accurate, the electrical and thermal properties of the materials that form the phantom should be accurately characterized. This paper reports on the experimentally measured thermal properties of two commonly used phantom materials, i.e. a rigid material with the electrical properties of human fat, and a low concentration polymer gel with the electrical properties of human muscle. Particularities of the two samples required the design of alternative measuring techniques for the specific heat and thermal conductivity. For the specific heat, a calorimeter method is used. For the thermal diffusivity, a method derived from the standard guarded comparative-longitudinal heat flow technique was used for both materials. For the 'muscle'-like material, the thermal conductivity, density and specific heat at constant pressure were measured as: k = 0.31 +/- 0.001 W(mK)(-1), p = 1026 +/- 7 kgm(-3), and c(p) = 4584 +/- 107 J(kgK)(-1). For the 'fat'-like material, the literature reports on the density and specific heat such that only the thermal conductivity was measured as k = 0.55 W(mK)(-1).

Evaluation Studies as Topic↗
PubMedDate not supplied

Electromagnetic thermal therapy power optimization for multiple source applicators.

The optimization of power deposition for electromagnetic (EM) thermal therapy is investigated. Several goal or objective functions are examined using a generalized mathematical formulation. These include maximization of: (1) target power absorption, (2) the ratio of target to non-target power absorption, (3) target power absorption weighted by the ratio of target to non-target power absorption, and (4) target power absorption subject to the constraint that the non-target high power volume ('hot spot' volume) is below a chosen level. The merit of these functions was retrospectively tested using an anatomic data base containing 38 cancer patients that were clinically heated with EM phased arrays. CT and/or MRI image data were used to define relevant anatomic geometries and tissue properties for finite element numerical models. Power optimization is achieved by variation of seven available control parameters (four amplitudes and three phases) for these clinical array devices. The results indicate that site dependent improvements in target power absorption can be achieved using these goal functions relative to a configuration that utilizes equal phase and amplitude for the sources. The relative merit among these various functions favours an optimization strategy that maximizes the target power absorption weighted by the ratio of target power to non-target power absorption.

Biophysical Phenomena↗
PubMedDate not supplied

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↗
PubMedDate not supplied

The effect of hydralazine dose on blood perfusion changes during hyperthermia.

Experiments were performed to determine the dose-related effects of the intravenous administration of a vasodilator (hydralazine) on normal muscle blood perfusion during localized hyperthermia. Fourteen anaesthetized outbred canines were investigated, seven receiving the recommended dose level of 0.5 mg/kg and seven receiving one-quarter of that level. The changes in blood perfusion were estimated using two methods: calculation of an effective blood perfusion magnitude and the use of state and parameter estimation techniques. Both methods showed that the changes in blood perfusion induced by the hydralazine were significant, and that the differences between the results for the two drug doses were not significantly different. This suggests that low doses may be useful in humans, giving the same resultant blood perfusion increase but with a decreased patient risk relative to standard therapeutic doses of hydralazine. While the trends in the blood perfusion changes were the same for both calculation methods the effective perfusion method frequently yielded blood perfusion magnitudes significantly different from those obtained using the state and parameter estimation technique. The differences are postulated to be due to the fact that the effective perfusion values include conduction effects, thus overpredicting the amount of perfusion present. Thus, while the effective blood perfusion can be used as a qualitative indication of blood perfusion changes under certain conditions, we do not recommend its use as a quantitative measure of perfusion.

Animals↗
PubMedDate not supplied

Towards the estimation of three-dimensional temperature fields from noisy temperature measurements during hyperthermia.

The temperatures at most locations are unknown during clinical hyperthermia because temperature data are obtained at only a few discrete locations. In an attempt to further develop a technique for possibly solving this problem, the feasibility of using state and parameter estimation methods to predict three-dimensional temperature fields during hyperthermia treatments is investigated. Previous studies attempting to solve this problem have been limited to only one or two spatial dimensions. This paper investigates some conditions for which an estimation method can predict the complete three-dimensional temperature field for controlled numerical experiments with additive measurement noise. For the range of perfusion patterns considered, results show that the steady-state temperature field can be estimated to within 1 degree C if there is no measurement noise, no model mismatch, and as few as three measurement locations for seven perfusion zones. The addition of measurement noise degrades the performance of this estimation algorithm, especially when the number of measurement locations is small. Use of Tikhonov regularization of order zero significantly improves the performance of the algorithm for these cases. It was found that there is an optimal regularization parameter which maximizes the algorithm performance. This optimal value is a function of the perfusion magnitude and pattern. The present numerical results indicate that the approach used to solve this difficult and ill-posed problem could potentially be extended to estimate the complete temperature field in more realistic clinical conditions, but considerably more progress must be made before that goal can be reached.

Algorithms↗
PubMedDate not supplied

Preliminary studies of interstitial hyperthermia using hot water.

A hot water interstitial hyperthermia unit was used to heat normal tissue in the thighs of rabbits and pigs. A 4 x 4 array of metal needles or plastic tubes spaced at 10 or 14 mm was implanted. Temperature measurements were made using five-sensor thermocouple probes inserted parallel to the implanted needles or tubes. With a water temperature of 48 degrees C, tissue temperature within the implant exceeded 42.5 degrees C when tube spacing was 14 mm and reached 47 degrees C when the spacing was 10 mm. However, at the lower water temperature of 45.5 degrees C inter-tube spacing was more critical, since the tissue temperature was above 43.5 degrees C for a spacing of 10 mm but below 42.5 degrees C for a spacing of 14 mm. Temperatures observed in vivo tended to be higher than those predicted by computer simulations, in which blood flow was assumed to be greater than that of resting muscle i.e. approximately greater than 0.45 kg m-3 s-1. The results show that an interstitial system using hot water can be a simple and efficient method of inducing hyperthermia.

Animals↗
PubMedDate not supplied

Application of new technology in clinical hyperthermia.

Two areas of technical progress related to hyperthermic oncology are presented: (1) numerical modelling of absorbed power and temperature distributions; and (2) non-invasive thermometry using magnetic resonance imaging. The results represent achievements made during the past 5 years at Duke University Medical Center's Departments of Radiation Oncology and Radiology. They represent examples of progress in the technology of hyperthermia that have potential for greatly improving the delivery, monitoring and assessment of clinical hyperthermia.

Body Temperature↗