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S T Clegg

Publications and source records attributed to S T Clegg.

18 recordsLinked to original sources
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

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↗
PubMedDate not supplied

Verification of a hyperthermia model method using MR thermometry.

Simulation of hyperthermia induced power and temperature distributions is becoming generally accepted and finding its way into clinical hyperthermia treatments. Such simulations provide a means for understanding the complete three-dimensional temperature distribution. However, the results of the simulation studies should be regarded with caution since modelling errors will result in differences between the actual and simulated temperature distribution. This study uses a diffusion weighted magnetic resonance (MR) based technique to measure hyperthermia induced temperature distributions in a three-dimensional space in a non-perfused phantom. The measured data are used to verify the accuracy of numerical simulations of the same three-dimensional temperature distributions. The simulation algorithm is a finite element based method that first computes the electromagnetic induced power deposition then the temperature distribution. Two non-perfused phantom studies were performed and qualitatively the MR and simulated distributions agreed for steady-state. However, due to the long MR sampling time (approximately 4 min), poor agreement between the simulations and MR measurements were obtained for thermal transients. Good agreement between the simulations and fibreoptic thermometry measurements were obtained. The fiberoptic measurements differed from the simulations by 0.11 +/- 0.59 degrees C and -0.17 +/- 0.29 degrees C (mean +/- standard deviation for the two studies).

Algorithms↗
PubMedDate not supplied

Simulation of electromagnetically induced hyperthermia: a finite element gridding method.

A finite element gridding method for simulating electromagnetically (EM) induced hyperthermia is presented. The method uses patient CT data as its primary input, with critical structures manually outlined (on a graphics workstation) for explicit demarcation. The paper outlines the various stages involved in mesh creation, including procedures for conforming the finite element representation of critical structures to their smooth boundaries, modelling of heating equipment, and modelling of the outer boundaries. The procedure for generating the finite element model is illustrated for an example treatment. Additionally, the results of computing the SAR in six patients are compared to measured values. The comparison reveals agreement between the model prediction and actual treatment within the limits of measurement error.

Combined Modality Therapy↗
PubMedDate not supplied

Estimation of cell survival in tumours heated to nonuniform temperature distributions.

UNLABELLED: A stochastic model describing the probability of cell survival as a function of thermal exposure was developed and fit to data arising from studies of CHO cell survival under hyperthermic conditions. This model characterizes the separate risks of temperature-induced cell death and induction of thermotolerance during heating. Tumour cells are assumed to be affected independently of each other by hyperthermia. Tumour geometry, perfusion and power deposition affect hyperthermia-induced temperature distributions in tumours, producing nonuniform temperatures. Two tumours may respond to hyperthermia slightly differently because of differences in tumour geometry, perfusion, power deposition, or by chance alone and the approach presented here incorporates chance and these other factors explicitly. THE RESULTS: (1) the time-temperature history is important for estimating tumour cell survival; (2) tumour temperature heterogeneity leaves more surviving cells at a given T90 temperature than would be expected if the entire tumour were uniformly heated to that same temperature; and (3) changes in the shape of the temperature distribution because of tumour geometry and perfusion distribution greatly influence cell survival between tumours, even when the standard temperature descriptors, such as T90, are fixed. The simulations also showed a modest effect on cell kill attributable to varying the lengths of the warm-up and the cool-down periods. These simulations indicate that these types of sensitivity studies can be used to investigate relationships between various modifiers of temperature distributions achieved when treating tumours with hyperthermia and to assess their potential therapeutic impact in clinical trials.

Animals↗
PubMedDate not supplied

Hyperthermia treatment planning and temperature distribution reconstruction: a case study.

While a great deal of effort has been applied toward solving the technical problems associated with modelling clinical hyperthermia treatments, much of that effort has focused on only estimating the power deposition. Little effort has been applied toward using the modelled power depositions (either electromagnetic (EM) or ultrasonic) as inputs to estimate the hyperthermia induced three-dimensional temperature distributions. This paper presents a case report of a patient treated with hyperthermia at the Duke University Medical Center where numerical modelling of the EM power deposition was used to prospectively plan the treatment. Additionally, the modelled power was used as input to retrospectively reconstruct the transient three-dimensional temperature distribution. The modelled power deposition indicated the existence of an undesirable region of high power in the normal tissue. Based upon this result, amplitudes and phases for driving the hyperthermia applicator were determined that eliminated the region of high power and subsequent measurements confirmed this. The steady-state and transient three-dimensional temperature distributions were reconstructed for four out of the seven treatments. The reconstructed steady-state temperatures agreed with the measured temperatures; root-mean-square error ranged from 0.45 to 1.21 degrees C. The transient three-dimensional tumour temperature was estimated assuming that the perfusion was constant throughout the treatment. Using the computed three-dimensional transient temperature distribution, the hyperthermia thermal dose was computed. The equivalent minutes at 43 degrees C achieved by 50% (T50Eq43) of the tumour volume was computed from the measured data and the three-dimensional reconstructed distribution yielding T50Eq43 = 40.6 and 19.8 min respectively.

Arm↗