Direct temperature measurement.

Hyperthermia has little hope of progressing as a clinical modality without accurate assessment of the temperature distributions obtained. At the present time only direct, invasive temperature-measuring techniques are possible, posing severe limitations. Established techniques for clinical temperature measurement have developed over the past few years, and for both ultrasound and electromagnetic hyperthermia it is possible to get temperature-time profiles at a large number of spatial points. Position uncertainty, thermal conduction smearing, and artifactual heating limit the accuracy to about 0.2 degrees (electromagnetic) or 0.5 degrees (ultrasound), but this is probably less of a hindrance than the inadequate percentage of tumor and normal tissue volume for which achieved temperatures can be documented.

Radiation therapy and hyperthermia improve the oxygenation of human soft tissue sarcomas.

The adverse prognostic impact of tumor hypoxia has been demonstrated in human malignancy. We report the effects of radiotherapy and hyperthermia (HT) on soft tissue sarcoma oxygenation and the relationship between treatment-induced changes in oxygenation and clinical treatment outcome. Patients receiving preoperative radiotherapy and HT underwent tumor oxygenation measurement pretreatment after the start of radiation/pre-HT and one day after the first HT treatment. The magnitude of improvement in tumor oxygenation after the first HT fraction relative to pretreatment baseline was positively correlated with the amount of necrosis seen in the resection specimen. Patients with <90% resection specimen necrosis experienced longer disease-free survival than those with > or = 90% necrosis. Increasing levels of tumor hypoxia were also correlated with diminished metabolic status as measured by P-31 magnetic resonance spectroscopy.

Anatomical site-specific modalities for hyperthermia.

The clinical application of hyperthermia in the treatment of deep-seated tumors remains an empirical science. The pleomorphic nature of the neoplasms and the great diversity in the anatomy and physiology of the individual tumor locations make the treatment of nearly every neoplasm a unique challenge. A wide variety of devices is required, both for the administration of hyperthermia and for the measurement of the temperatures achieved. At Stanford University, these include the BSD Medical Corp. annular phased array system, an isospherical ultrasound device, and interstitial radiofrequency for deep heating. Ultrasound transducers and a variety of microwave applicators are used for superficial hyperthermia. Six illustrative case studies, selected from the 91 patients treated in our program since October 1981, are presented, with discussion and comparison of treatment devices. Difficulties in deep heating were encountered in several instances, believed secondary to the thickness of the s.c. fat, the relatively high heat-induced tumor blood flow, and the presence of adjacent bone. It is suggested that ultimate improvement in clinical results will be possible once a better understanding is achieved of such anatomical and physiological factors.

Improved coupling of ultrasound hyperthermia applicators to patients.

Coupling ultrasound (US) hyperthermia (HT) applicators to patients requires an acoustical medium conforming to both applicator and patient that allows for rapid, reproducible set-up for each treatment and prevents drift or misalignment of the applicator during treatments. We describe a technique that uses a commercially available immobilization foam to create a rigid, conforming foam block that kinematically positions the US applicator over the tumor area. The central volume of the foam block is removed and filled with a plastic bag of degassed water or with US gel during treatments. We also describe a technique for positioning surface and interstitial thermometry sensors in alignment with individual elements of a multi-element US applicator. Using these techniques, relative movement between patient and applicator is minimized, correct thermometry sensor location relative to each US element is confirmed, and efficient transmission of the acoustical power into the target volume is assured. These techniques are particularly important when using multi-element applicators with complex temperature-power control algorithms.

Temperature measurements in high thermal gradients: I. The effects of conduction.

Two temperature probes (a fluoroptic sensor and a metallic thermistor), which are both suitable for stereotaxic implantation, were used in comparative thermometry studies during interstitial microwave heating of the brain in vivo. Thermal distributions having large temperature gradients (5-10 degrees C/cm) were routinely observed. The temperature differentials (delta T) between the 2 probes were position dependent within the thermal field. The maximum difference in temperatures measured, using the 2 probes along identical tracks without a catheter, ranged between 0.5 degree C and 1.8 degree C. Near the brain/air surface, the thermistor measured lower temperatures than the optical probe; however, medial to the antenna, the thermistor temperatures were higher than the optic sensor. The measured temperature discrepancies are the result of smearing due to thermal conduction along the axial length of the metallic thermistor probe. These effects are significantly accentuated when the temperature probes are tracked in catheters. Experiments performed in a nonperfused phantom, heated with the interstitial microwave antenna, demonstrated similar conductive effects. Studies in a nonelectromagnetic environment (flow cell-thermal step gradient) additionally confirmed that thermal conductive artifacts were the major source of temperature error.

Temperature measurements in high thermal gradients: II. Analysis of conduction effects.

Measurement errors associated with thermal conduction along a temperature probe in regions of high thermal gradients are examined. An analysis of a conducting probe inserted into an insulating catheter for the purpose of temperature mapping gives a means for estimating the effects of thermal smearing on the measured distribution. A comparison is made between the theory and an experimental test case (flow cell-thermal step gradient). Also, an iterative algorithm is developed to correct thermally smeared temperature distributions in order to reconstruct the desired unsmeared distributions. The algorithm is checked for self consistency in the flow cell experiment and is applied to in vivo data obtained during interstitial microwave heating in normal dog brain. Data from flow cell measurements are used to make relative comparisons of the probe conduction artifact for several different temperature probes (2 thermocouple needle probes, a thermistor needle probe and an optical probe) and assorted teflon catheters (16, 18 and 20 ga).

Heating deep seated eccentrically located tumors with an annular phased array system: a comparative clinical study using two annular array operating configurations.

Regional heating administered with an annular array to 12 patients with deep-seated advanced malignant disease eccentrically located in the lower abdomen and pelvis is compared based on the annular array operating configuration. One configuration (4 quadrants active) delivers radiofrequency power with relative uniformity throughout the patient cross-section. The other (2 quadrants active) allows the radiofrequency power deposition to be shifted preferentially into the eccentrically located treatment volume. Phantom measurements have been made to demonstrate the redistribution of radiofrequency power that results when the annular array is operated in these respective configurations. Systemic responses (i.e. oral temperature rise, changes in blood pressure, and heart rate) to these regional hyperthermia applications are compared and are not significantly different with respect to these heating configurations. Temperature data obtained during treatment sessions using these two annular array operating configurations are analyzed based on the fraction of measured tumor and normal tissue temperatures exceeding or equal to a given index temperature. Although the two quadrant configuration is more efficient in delivering power to the treatment volume, this analysis does not indicate a significant gain in therapeutic heating as a result of this preferential power deposition. Treatment tolerance and heterogeneity with respect to tissue type and blood flow remained the dominant limiting factors with regard to temperatures achieved.

Correlations of thermal washout rate, steady state temperatures, and tissue type in deep seated recurrent or metastatic tumors.

The rates of cooling ("thermal washout") in selected sites in tumor and adjacent normal tissues following the completion of clinical hyperthermia sessions were analyzed in ten patients treated with combined radiation and hyperthermia for deep seated recurrent or metastatic tumors. The temperatures were recorded at 10 second intervals for at least 2 minutes after the cessation of microwave power at the end of the 30-60 minute duration hyperthermia treatments. These thermal washouts were characterized by the slope of a log-linear relation between temperature elevation above the oral baseline temperature and time. Washout rates (expressed as a perfusion rate in ml/100g-min) significantly correlated with tissue categories as noted on CAT scan (i.e., tumor, normal tissue, tumor/normal tissue interface, hypodense tumor areas). Relationships between thermal washout rate and steady-state temperature elevation were tested and also showed significant correlations in general and for some specific tissue categories. The implications of these findings in explaining inhomogeneities in heating patterns, and in hyperthermia treatment modeling will be presented.

Combined external beam irradiation and external regional hyperthermia for locally advanced adenocarcinoma of the prostate.

PURPOSE: To determine the safety and efficacy of combined external beam irradiation and external regional hyperthermia in the treatment of adenocarcinoma of the prostate. METHODS AND MATERIALS: From 1987 to 1994, 30 patients received combined external beam irradiation and external regional hyperthermia for locally advanced prostate cancer. The results of the 21 patients with newly diagnosed (n = 18) or locally recurrent (n = 3) adenocarcinoma are reported herein. No patient had evidence of distant metastases. Total radiotherapy doses of 65-70 Gy to the prostate were planned using a four-field box technique. Hyperthermia treatments were delivered using an annular phased array microwave device. The treatment goal was to achieve temperatures > or = 42 degrees C in all measured points within the prostate. RESULTS: Of the newly diagnosed patients, 16 out of 18 (89%) had T3 or T4 tumors, 11 out of 18 (61%) had Gleason scores of 7-9, and the mean pretreatment Prostate Specific Antigen (PSA) was 69 ng/ml. The median follow-up of all 21 patients was 36 months. None of the patients achieved the treatment goal of all intratumoral temperatures > or = 42 degrees C. The mean CEM 43 T90 was 2.34 min. The disease-free survival at 36 months is 25%; 12 out of 18 (67%) of the patients have relapsed. The only significant predictor of relapse was pretreatment PSA. There were no complications > Grade 3. CONCLUSIONS: In spite of the inability to achieve high tumor temperatures, the relapse-free survival rate in this population of patients with very advanced localized prostate cancer treated with radiation therapy plus hyperthermia compares favorably with most series using radiation therapy alone. Further studies aimed at improving the ability to deliver hyperthermia to the prostate are warranted.

Phase I/II study of external radio frequency phased array hyperthermia and external beam radiotherapy in the treatment of prostate cancer: technique and results of intraprostatic temperature measurements.

As part of an ongoing Phase I/II study at Duke University Medical Center investigating the toxicity and efficacy of external beam radiotherapy plus hyperthermia for deep-seated, locally advanced or recurrent solid tumors, 12 patients with prostate malignancies (adenocarcinoma--11, leiomyosarcoma--1) were treated with radiotherapy plus hyperthermia. Hyperthermia was given after radiotherapy using a Radio Frequency Phase/Amplitude Control Sigma 60 annular phased array device. All patients had simultaneous temperature measurements made in the rectal lumen and within the prostate during at least one hyperthermia session. Intraprostate thermometers were placed via a unique method described herein using both computerized tomography scan and a rigid sigmoidoscope for guidance. We were able to achieve the desired tumor temperature of > or = 42.5 degrees C in only 1/28 (3.5%) of hyperthermia treatments. Subjective symptoms of pain and/or pressure limited power deposition in 79% of hyperthermia treatments. Higher temperatures were achieved in the distal rectum than in the prostate in all treatments, although the differences were not statistically significant. This temperature differential could not be compensated by using phase and amplitude steering. Rectal temperatures adjacent to the prostate were predictive of prostate temperatures. We conclude that using this regional heating technique we were unable to demonstrate an ability to get an advantageous temperature differential between the prostate and normal tissue. This technique is not useful as an adjuvant to radiation therapy for prostate cancer. The usefulness of other regional heating techniques and devices should be explored.

Spiral microstrip hyperthermia applicators: technical design and clinical performance.

Spiral microstrip microwave (MW) antennas have been developed and adapted for use as clinical hyperthermia applicators. The design has been configured in a variety of forms including single fixed antenna applicators, multi-element arrays, and mechanically scanned single or paired antennas. The latter three configurations have been used to allow an expansion of the effective heating area. Specific absorption rate (SAR) distributions measured in phantom have been used to estimate the depth and volume of effective heating. The estimates are made using the bioheat equation assuming uniformly perfused tissue. In excess of 500 treatments of patients with advanced or recurrent localized superficial tumors have been performed using this applicator technology. Data from clinical treatments have been analyzed to quantify the heating performance and verify the suitability of these applicators for clinical use. Good microwave coupling efficiency together with the compact applicator size have proved to be valuable clinical assets.

Preoperative hyperthermia and radiation for soft tissue sarcomas: advantage of two vs one hyperthermia treatments per week.

As part of an ongoing Phase II trial at Duke University Medical Center (DUMC), patients with Stage IIB-IVA soft tissue sarcomas (STS) potentially amenable to wide local excision were treated with preoperative hyperthermia (HT) plus radiation therapy (RT), with HT randomized to one versus two treatments per week, stratified with respect to tumor volume. 17 patients were treated and analyzed. HT was given 30-60 minutes after RT, with heating maintained for 1 hour after 42.0 degrees C was reached. In patients treated with 2 HT per week, treatments were separated by 48 hrs. Concurrent RT was given with 180-200 cGy fractions, five treatments per week, to a nominal tumor dose of 5000-5040 cGy. Surgical extirpation was performed 4 weeks after completion of HT/RT. Treatment effect was evaluated by histopathologic examination of the resected lesions, according to a previously reported system. The mean number of HT given in the 1 and 2/wk groups was 4.4 and 7.3, respectively (p less than 0.01). Tmax for the 1 and 2 HT/wk groups was 42.4 +/- 2.1 degrees C and 43.5 +/- 1.8 degrees C, and T min was 38.1 +/- 0.8 degrees C and 38.6 +/- 0.5 degrees C, respectively. The increase in T min from first to last treatment was 0.5 +/- 1.2 degrees C and 1.0 +/- 0.8 degrees C, respectively. The T min from the best treatment was 39.1 +/- 1.2 degrees C and 40.0 +/- 1.0 degrees C, and the Tmax from the best treatment was 44.5 +/- 3.4 degrees C and 45.4 +/- 2.5 degrees C for the 1 and 2 HT/wk groups, respectively. There were no statistically significant differences between the 2 treatment groups for any of the above temperature parameters. Severe histopathologic changes were found in 71% (12 of 17) of the lesions. T min and Tmax and highest T min and Tmax were between 0.4-1.1 degrees C higher in patients with severe changes (p = NS). All 9 patients in the 2 HT/wk group had extensive changes, versus only 3 of the 8 patients in the 1 HT/wk group. This difference was highly statistically significant (p = 0.009, two-tailed Fisher's exact test). These findings suggest an advantage to twice weekly, as opposed to weekly, HT in the setting of this study. Whether there is a corresponding therapeutic gain, or whether these results can be extrapolated to other settings requires further investigational efforts. It is recommended that treatment parameters, particularly temperature parameters, continue to be examined in Phase II trials.

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.

RTOG quality assurance guidelines for clinical trials using hyperthermia administered by ultrasound.

Clinical quality assurance guidelines are established for RTOG hyperthermia protocols in which unfocused planar ultrasound may be used to administer hyperthermia. Measurement of temperature at a few fixed points is no longer considered to be adequate. Thermal mapping is required to obtain profiles of the temperature across the tumor dimensions, including margins of normal tissue. The thermometry strategies established for microwaves are to be adhered to with oblique insertion of the probes recommended. Two types of errors arise which are generally not present with microwaves. A measurement error, commonly referred to as a temperature artifact, arises because of absorption and/or viscous heating of the probe. Another error arises when thermocouples are used due to the conduction of heat along the wire leads, especially the copper wire. Several thermometry systems are evaluated with regard to the expected artifact and conduction errors. Acceptable systems include: a) indexing a polyurethane sheathed single sensor thermocouple in a polyurethane catheter, b) indexing a fiberoptic probe in a steel needle, c) indexing a single sensor thermocouple in a steel needle, and d) use of manganin-constantan multisensor thermocouples. Unacceptable systems include: a) fixed or static probes that do not provide profiles of the temperature across the tumor dimensions, b) copper-constantan multisensor thermocouples, and c) teflon sheathed thermocouples inserted into a teflon catheter.

Cumulative minutes with T90 greater than Tempindex is predictive of response of superficial malignancies to hyperthermia and radiation.

PURPOSE: To better define thermal parameters related to tumor response in superficial malignancies treated with combined hyperthermia and radiation therapy. METHODS AND MATERIALS: Patients were randomized to receive one or two hyperthermia treatments per week with hyperthermia given during each week of irradiation. Hyperthermia was given for 60 min with treatments begun within 1 hr following irradiation. Power was increased to patient tolerance or normal tissue temperature of 43.0 degrees C. Irradiation was generally given 5 times per week with doses prescribed to normal tissue tolerance (generally 24-70 Gy at 1.8-2.5 Gy per fraction). Multipoint thermometry was used with temperatures obtained every 5 min. RESULTS: One hundred eleven individual treatment fields containing 1 or more tumor nodules were completely evaluable. The complete and overall response rates were 46% and 80%, respectively. Forty-one percent of all treatment fields (51% of responding lesions) remained controlled at 2 years. Multivariate analysis revealed that the cumulative minutes that the temperature achieved by 90% of the measured tumor sites (T90) was > or = 40.0 degrees C, tumor histology, tumor volume, and radiation dose were significantly associated with complete tumor response. The complete response rate was not significantly affected by the number of hyperthermia treatments given per week. The incidence of clinically significant complications was low. CONCLUSIONS: These results support the usefulness of the cumulative minute system in describing time-temperature relationships. The significance of thermal variables with regard to tumor response strongly supports the contention that hyperthermia can be a useful adjunct to irradiation for the local control of cancer.

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.

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).

Tumor temperature distributions predict hyperthermia effect.

Review of clinical hyperthermia (HT) trial results shows that there previously has not been a robust model relating efficacy of HT treatments to characteristics of the temperature distribution. Lack of a model has been an impediment in Phase II trials; these trials must include defining the prescription for HT treatment, optimizing the schedule of HT treatments, and defining quality assurance procedures. We propose a model that is based upon noting that the majority of a tumor volume is contained in the outermost "shell" of a solid tumor, across which shell the radial temperature distribution is assumed to be linear. Any linear distribution can be defined by coordinates of a point and a slope, and we choose the temperature at the radiographically defined edge of a tumor and the slope (dT/dr) across the outer shell as these determinants of the linear radial temperature distribution. A discriminant analysis of success or failure of treatment can then be based upon these two descriptors (Tedge, dT/dr). We have tested this model using data from patients with soft tissue sarcoma (Stage IIB or greater) that have entered an ongoing prospective trial of conventional preoperative radiotherapy (5000 cGy/25 Fx/5 wk) together with HT, the latter randomized to be given once or twice weekly during the 5 week course. Wide local excision of the primary tumor is done 1 month after completion of radiotherapy, and the extent of histologic change in the resected specimen is scored. Our model has an 86% predictive value for lack of complete or nearly complete necrosis in the resected specimen according to whether the time-averaged Tedge and slope during each HT treatment satisfy the equation Tedge + 1.2 (slope in degree C/cm) less than or equal to 40.6 degrees C in all but one treatment at most. Conversely, in 85% of cases with complete or nearly complete tumor necrosis, temperature distributions satisfied Tedge + 1.2 (slope in degree C/cm) greater than 40.6 degrees C during at least one HT treatment. Requiring greater than or equal to one third of treatments of a patient to satisfy the preceeding discriminant equation resulted in 80% of patients being correctly classified as a responder or nonresponder, with only one false positive prediction (patient incorrectly classified as a responder). The model can reveal systematic changes in the edge temperature distribution during the treatment course that are consistent with tumor perfusion changes inferred and measured by independent means.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

Use of nitroprusside to increase tissue temperature during local hyperthermia in normal and tumor-bearing dogs.

The present study investigates the effects of nitroprusside, a potent vasodilating agent, on tissue temperature during local hyperthermia in five normal and five tumor-bearing dogs. Caudal thigh muscles were heated in normal dogs and muscle temperatures were recorded during hyperthermia. Tumor-bearing dogs received two hyperthermia treatments during a course of radiation therapy. Temperatures were recorded in tumor and surrounding normal tissues. Mean arterial pressure was decreased by approximately 40-45% during nitroprusside infusion and was associated with a compensatory increase in heart rate and increases in tissue temperature. In normal dogs, muscle temperatures increased an average of 1.7 degrees C with nitroprusside administration. When nitroprusside was administered at the beginning of local hyperthermia to induce step-down heating, approximately 48% of the measured positions in caudal thigh muscle achieved a temperature greater than or equal to 43 degrees C, sufficient to induce step-down heating, during the hyperthermia episode. In tumor-bearing dogs, there was a significant increase in tumor and normal tissue temperatures during nitroprusside administration. Estimated T90 and T50 descriptors increased by 0.9 degrees C and 1.6 degrees C, respectively, for tumor tissue and by 0.4 degrees C and 1.2 degrees C, respectively, for normal tissue. Despite the increase in normal tissue temperatures no toxicity was observed in these dogs. Nitroprusside may be a useful agent for manipulation of tumor temperatures during the entire hyperthermia treatment or for a short time period at the initiation of treatment to induce step-down heating.