SESSION 1

THERAPEUTIC PROCESSES - I

Chairman: A. Shitzer

This is a report on a three-day workshop held at the Allerton House of the University of Illinois. The first day consisted of invited tutorials on topics related to biothermal engineering: biological structures, analysis of microvascular heat transfer, temperature measurement, cryobiology and cryosurgery, burns, and industrial and consumer applications.

The rest of the workshop consisted of discussions in small groups and in plenary sessions dealing with relevant topics. Although the discussions endeavored to be as comprehensive as possible, the specific topics were selected by the participants based on their expertise and interests.

The main areas examined were:

Instrumentation

Priority applications

Mathematical modeling

Thermal injury

The reliable measurement of the temperature distribution inside the living tissue is still the premier problem of instrumentation although the measurement of other parameters, such as properties, blood perfusion or heat flux, is also of great importance.

The most important applications are medical, industrial, consumer, agricultural, space, and military. The degree of sophistication needed in the analysis of specific problems varies a great deal from relatively simple heat conduction models to complicated ones including blood perfusion, anisotropy, and the influence of large blood vessels. For many applications new experimental data are still needed.

There have been significant advances in the modeling of living tissue with increasing understanding of its thermal behavior. The consensus was, however, that the models will always have to be tissue or organ specific and some new models are still to be developed.

INTRODUCTION

Benign prostatic hyperplasia (BPH) is a serious disease that generally occurs in elderly men. Most of these individuals are in the high surgical risk group. As an alternative to surgery, one of the recently developed therapeutic modalities is the local hyperthermia induced either by the microwave or the radio frequency (RF) heating. Histologically, prostatic hyperplasia develops spontaneously in both the dog and human. Since the natural history of this condition in the dog is remarkably similar to that in the human, the dog has been widely used in experimental studies to examine the effectiveness of the microwave or the RF hyperthermia for BPH.

Recent studies on the transurethral-applied local hyperthermia in the canine and human prostate have revealed significant effects of natural thermoregulation on the therapeutical results. It has been long recognized that a major factor that affects tissue temperature elevation and heterogeneity during hyperthermia, is the augmentation of blood flow concomitant with the heating. In the present study, using the thermal pulse decay (TPD) technique, blood perfusion rates were measured in different regions within the canine prostate during transurethral heating. Relationships of the blood perfusion, power deposition, and tissue temperature were observed and analyzed.

METHODS

During the microwave hyperthermia, fourteen male mongrel dogs (wt. 21.9 ± 3.1 kg) over four years old were used for blood perfusion studies. Dogs were anesthetized using Na-pentobarbital, i.v. (30 mg/kg). The bladder and prostate were exposed through a midventral abdominal incision. A small cut was made in the bladder wall to allow insertion of the transurethral thermal therapy (T3) catheter (Urologix, Inc. MN) into the prostatic urethra. Within the catheter, a microwave antenna is located approximately in the center and chilled water at a given temperature flows between the antenna and the inner catheter wall. A fiber optic thermosensor built inside of the catheter monitored the prostatic urethral wall temperature throughout each experiment.

Thermistor bead probes of different lengths were placed at various locations within the prostatic tissue. These probes serve two purposes: thermal pulse delivery and local temperature measurement. The blood perfusion rate and tissue thermal conductivity was measured simultaneously in the canine prostate using the thermal pulse decay (TPD) technique. This technique is based on a comparison of the measured with the model simulated temperature decay following a heating pulse delivered by a thermistor bead probe. A solution of the Pennes bio-heat transfer equation is used to construct the theoretical model relating local blood perfusion to the temperature decay.

To study the instantaneous blood perfusion response to the local tissue temperature increase, the RF heating was applied to the canine prostate using the EESY- 100 RF Prostatic Hyperthermia System (Yuanshui Industrial Co. PRC). The use of the RF heating was intended in this part of the study to ensure a broad uniformly heated tissue region for examination of the blood perfusion response. Nine male mongrel dogs (wt. 21.9 ± 3.1 kg) over four years old were used. A thermocouple built inside the RF catheter was used to monitor the urethral wall temperature throughout the entire experiment.

Experimental data are shown as mean ± standard deviation (SD). Differences among the mean values were determined by one-way repeated measures ANOVA using SYSTAT software. The post hoc comparisons between any two levels were performed by the modified student t-test.

RESULTS AND DISCUSSIONS

Microwave Heating

Results indicate that, under the normal condition, the periurethral region is most highly perfused with an average rate of 0.60±0.25ml/min/gm (n=4) while the perfusion rate is 0.34±0.22ml/min/gm (n=10) in parenchyma. An approximately 3.5 fold increase in perfusion from the respective baselines was observed in both regions when the local tissue temperature was raised to 41.5oC by the microwave heating. Another 0.5 fold increase was found in parenchyma after the tissue was further heated to 43.1oC at which oscillatory behaviors in tissue temperature have been observed. In general, the present baseline perfusion falls within the range of 0.20 - 0.79 ml/min/gm, the measured average perfusion rate throughout the entire canine prostate via different techniques from previous studies. Use of the TPD technique in this study has enabled us to examine blood perfusion in different regions within the prostate. The periurethral perfusion was significantly higher than that in the parenchymal region at the baseline and 10W microwave heating level. This could be partially attributed to the fact that in the prostate gland, the periurethral region is supplied by the artery of the urethral bulb while the parenchyma is perfused by radial tributaries from the subcapsular artery passing along the capsule septa toward the urethra. Thus, the baseline and the response of blood perfusion to the microwave heating would likely be different in these two regions.

RF Heating

As revealed earlier, there was no significant increase in perfusion observed in the prostate under the 5W microwave heating. Blood perfusion response to the RF heating was therefore observed only at the 10W and 15W level. Two interesting phenomena have been found. First, the oscillatory temperature behavior seems to be coupled with an oscillatory change in blood perfusion. Within each cycle, the change in perfusion appears to be closely related to not only the tissue temperature but also the temporal temperature gradient. Second, the maximal perfusion and interstitial temperature occurred almost at the same moment that was several minutes behind the time when the maximal urethral wall temperature was reached. Since both the urethral wall and interstitial temperatures are regulated by blood perfusion, it is not difficult to see that blood perfusion acts as a feedback of the local tissue temperature in a closed control system.

CONCLUSION

In this study, a close relationship of blood perfusion to local tissue temperature and its temporal gradient has been observed. It seems that all the physiological factors which influence the change of blood flow, are most likely stimulated by the thermal field rather than the non-thermal effects from the electromagnetic fields. Results from this study will not only help to improve the efficacy of hyperthermia treatment, but more importantly to provide a better understanding of thermoregulation in biological systems during hyperthermia.

ACKNOWLEDGMENT

This research was supported by NIH 5 R29 CA67970. Authors wish to thank Urologix, Inc. and Yuanshui Industrial Company for providing the transurethral thermal therapy systems and technical assistance to this research. Many thanks are also extended to Mr. David Y. Yuan and Dr. Lie-Wen Pang for their great assistance to this experimental study.

INTRODUCTION

In everyday life, during high intensity heating technological processes, receiving and storing of highly inflammable fuels and explosives one can always run into the danger of getting burn injury under intensive heat influence.

Purposeful search of heat protection materials is impossible without testing them with reliable quantitative estimation of human injuring level.

The most objective estimation may be received during natural tests, but such tests demand considerable material and intellectual expenditures.

The most widely used laboratory methods of testing of heatprove characteristics of cloth is the standard method TPP (Thermal Protective Performance Test). According to this method critical energy is used as burn injury criterion [1].

Analysis of literature data [1-5] shows, that threshold meaning of heat impulse, causing injury is a variable quantity. Range of changing of this quantity at intensive heating influence may be considerable.

It is known the appearance of injury and changes connected with it in organism depend on intensity and depth of tissue heating [3].

However results of temperature profile measuring in skin of warm-blooded animals are not given in literature. Application of tissue thermometric method for this purpose is not correct, because dimensions even of a small temperature sensoring element are compared with thickness of heated skin level.

Therefore, for determination of temperature profile in skin cover and basing of temperature criterion of thermal burns it is necessary to search other methods. One of them may be the method of mathematical modeling.

In this study, a complex method is suggested for determination of skin temperature field; it includes mathematical simulation of heat transfer process in skin cover during the time of influence of thermic agent and experimental reproduction of burn injury with measurement of given temperature on animal body surface done beforehand.

MATHEMATICAL FORMULATION

For calculation of temperature according to depth of skin cover we carried out mathematical model of heat transfer process. In this model the difference of thermophysical properties of structural skin layers was taken into account.

Mathematical description of model may be represented in the following way. Three-layered cylinder, with different coefficients of layer temperature conductivity has the initial temperature T = 37^o C. During period of time - time of thermo agent influence, causing second-degree burn) temperature of external surface (x = 0) under influence of heat source is mounted equal to T₁. In region it is necessary to build the solution of differential heat conductivity equation

...(1)

satisfying the following initial and boundary conditions

...(2)

at ...(3)

at the rest part of bounder of area (except line r=0)

...(4)

where n - normal to area bounder.

CALCULATION RESULTS AND DISCUSSION

The program of initial task solution is composed so that it allows to receive temperature distribution in skin cover at any low of temperature change on body surface.

The mathematical modeling of heat distribution in skin cover layers for different geometric sizes of heated zones r, R & z and different time of increased temperature t^* influence was carried out. The results of modeling have shown that the sizes of the central part of the spot on which condition of one dimensional heat distribution are 0.7 - 0.9 r during all period of heating.

That is why in the experiments with burns, the size of round heating element were 20 mm. Inside of this spot in zone with diameter 15 mm the temperature difference between one dimensional and two dimensional cases is not more than 3 %. That is considerably less than statistic mistake of burn reproduction. On the other hand, the spot with diameter 15 mm is quite sufficient for clinic estimation of burn injury.

Changes of temperature in each structural skin layer to the time moment t^* are shown as example in Fig. 2. These changes were received by calculation process for experimental meanings of surface temperatures.

From presented results it is seen that irrespective of temperature profile in studied range of surface temperatures second-degree burn and more appear in time period, when temperature of nipple layer of dermis reaches the critical magnitude (49^oC).

According to data of physiologists, that is the exact temperature when the death of heat receptors in derma occurs, and it seems to be the reason of breach of physiologic skin thermoregulation, that leads to pathologic changes.

SUMMARY

• Critical temperature of skin cover under epidermis boundary causing second-degree injury was determined by method of mathematical simulation.
• The instrumental method of heatprotecting material properties evaluation was suggested with the usage of critical temperature criterion.

REFERENCES

1. Behnke W.P., Predicting Flash Fire Protection of Clothing from Laboratory Tests Using Second-degree Burn to Rate Performance. Fire and Materials., Vol.8, No. 2, pp 57-63, 1984.
2. Stoll A.M., Hardy J.D., Greene L.C., J. Appl. Physiol., 15, 489, 1960.
3. Stoll A.M. "The Role of Skin in Heat Transfer" in "Advances in Heat Transfer", (ed. by Hartnett, J.P. and T.F. Irvine), Academic Press, New York, , Vol. 4, p.115, 1967.
4. Stoll A.M., and Chianta M.A., Method and Raiting System for Evalution of Thermal Protection, Aerosp. Med. 40 (11), pp 1232-1238, 1969.
5. Barker R.L. and Lee Y.M. Analyzing the Transient Thermophysical Properties of Heat-resistant Fabrics in TPP Exposure, Textile Research Journal, June, pp 331-338, 1987.