Thermal effects of a short light flash on biological tissues. I. An optical and thermal model

By summarizing the reference data and own calculations, a simple model for the optical and thermal properties of two-component biological tissues was proposed, as applied to the investigations of thermal fields in human tissues under external irradiation. The model comprises a small number of input variable parameters (total hemoglobin, blood oxygenation degree, and volume fraction of blood vessels) and enables one to find all optical characteristics necessary to compute the light fields in the tissue and set the thermal source function. Thermal parameters that determine heat transfer in the two-component medium were calculated with regard for the conditions of heat exchange between the components and heat transfer at the interface with various environments.     

New mathematical model to estimate tissue blood perfusion, thermal contact resistance and core temperature

Analytical solutions were developed based on the Green's function method to describe heat transfer in tissue including the effects of blood perfusion. These one-dimensional transient solutions were used with a simple parameter estimation technique and experimental measurements of temperature and heat flux at the surface of simulated tissue. It was demonstrated how such surface measurements can be used during step changes in the surface thermal conditions to estimate the value of three important parameters: blood perfusion (w(b)), thermal contact resistance (R"), and core temperature of the tissue (T(core)). The new models were tested against finite-difference solutions of thermal events on the surface to show the validity of the analytical solution. Simulated data was used to demonstrate the response of the model in predicting optimal parameters from noisy temperature and heat flux measurements. Finally, the analytical model and simple parameter estimation routine were used with actual experimental data from perfusion in phantom tissue. The model was shown to provide a very good match with the data curves. This demonstrated the first time that all three of these important parameters (w(b), R", and T(core)) have simultaneously been estimated from a single set of thermal measurements at the surface of tissue.     

Temperature regime of biological tissue under photodynamic therapy

An analytical model is proposed to calculate heating of human skin cover under laser light action of photodynamic therapy. A photosensitizer of "Fotolon" is taken as an example. Temperatures of skin surface and of deep dermis regions are studied as a function of time under pulsed and stationary irradiation of skin surface at the wavelength of 665 nm corresponding to the maximum of the photosensitizer absorption band. It is shown that, under the action of a short light pulse, the photosensitizer can lead to an essential temperature rise of dermis due to a considerable increase in its absorption coefficient. However, this rise does not destruct tissue cells because of the short action. Under stationary irradiation, the photosensitizer concentration has a low effect on the temperature regime of tissue. This is related with the specific features in heating of the medium by red light, where the main thermal process in skin is heat transfer over tissue volume from epidermis having a substantially larger absorption coefficient than that of dermis in the said spectral range. The role of blood perfusion in dermis and its effect on the temperature regime of tissue are evaluated.     

Temperature regime of biological tissue under photodynamic therapy

An analytical model is proposed to calculate heating of human skin cover under laser light action of photodynamic therapy. A photosensitizer of «Fotolon» is taken as an example. Temperatures of skin surface and of deep dermis regions are studied as a function of time under pulsed and stationary irradiation of skin surface at the wavelength of 665 nm corresponding to the maximum of the photosensitizer absorption band. It is shown that, under the action of a short light pulse, the photosensitizer can lead to an essential temperature rise of dermis due to a considerable increase in its absorption coefficient. However, this rise does not destruct tissue cells because of the short action. Under stationary irradiation, the photosensitizer concentration has a low effect on the temperature regime of tissue. This is related with the specific features in heating of the medium by red light, where the main thermal process in skin is heat transfer over tissue volume from epidermis having a substantially larger absorption coefficient than that of dermis in the said spectral range. The role of blood perfusion in dermis and its effect on the temperature regime of tissue are evaluated.     

The effect of media tonicity on Escherichia coli resistance to heating with different gradient

The influence of NaCl water solutions and glycerine hypertonic concentration on the survival of bacteria Escherichia coli B/r heated with different values of heat drop was investigated. It was shown that the transfer of cell suspensions from isotonic conditions to media with raised osmotic pressure, preliminarily heated up to 60 degrees C, and the following heating at this temperature inhibited differences in cell sensitivity to heating at different heat drop. Unlike, it was found that the transfer of cell suspensions from isotonic conditions to hypertonic media before and after heating at 60 degrees C increased differences in resistance of these microorganisms to heating at different heat drop. It is proposed that different resistance of bacteria to damaging action of hyperthermia at different heat drop, and a modified influence of hypertonic solutions on these differences may be due to heat induced destabilization of cell osmotic homeostasis. The extent of expression of this destabilization may be determined by a quantitative ratio of osmotic pressure values in the cell-suspension medium system in particular temperature and tonic environmental conditions.     

Numerical study on the thawing process of biological tissue induced by laser irradiation

Most of the laser applications in medicine and biology involve thermal effects. The laser-tissue thermal interaction has therefore received more and more attentions in recent years. However, previous works were mainly focused on the case of laser heating on normal tissues (37 degrees C or above). To date, little is known on the mechanisms of laser heating on the frozen biological tissues. Several latest experimental investigations have demonstrated that lasers have great potentials in tissue cryopreservation. But the lack of theoretical interpretation limits its further application in this area. The present paper proposes a numerical model for the thawing of biological tissues caused by laser irradiation. The Monte Carlo approach and the effective heat capacity method are, respectively, employed to simulate the light propagation and solid-liquid phase change heat transfer. The proposed model has four important features: (1) the tissue is considered as a nonideal material, in which phase transition occurs over a wide temperature range; (2) the solid phase, transition phase, and the liquid phase have different thermophysical properties; (3) the variations in optical properties due to phase-change are also taken into consideration; and (4) the light distribution is changing continually with the advancement of the thawing fronts. To this end, 15 thawing-front geometric configurations are presented for the Monte Carlo simulation. The least-squares parabola fitting technique is applied to approximate the shape of the thawing front. And then, a detailed algorithm of calculating the photon reflection/refraction behaviors at the thawing front is described. Finally, we develop a coupled light/heat transport solution procedure for the laser-induced thawing of frozen tissues. The proposed model is compared with three test problems and good agreement is obtained. The calculated results show that the light reflectance/transmittance at the tissue surface are continually changing with the progression of the thawing fronts and that lasers provide a new heating method superior to conventional heating through surface conduction because it can achieve a uniform volumetric heating. Parametric studies are performed to test the influences of the optical properties of tissue on the thawing process. The proposed model is rather general in nature and therefore can be applied to other nonbiological problems as long as the materials are absorbing and scattering media.     

Temperature evolution in tissues embedded with large blood vessels during photo-thermal heating

During laser-assisted photo-thermal therapy, the temperature of the heated tissue region must rise to the therapeutic value (e.g., 43 °C) for complete ablation of the target cells. Large blood vessels (larger than 500 micron in diameter) at or near the irradiated tissues have a considerable impact on the transient temperature distribution in the tissue. In this study, the cooling effects of large blood vessels on temperature distribution in tissues during laser irradiation are predicted using finite element based simulation. A uniform flow is assumed at the entrance and three-dimensional conjugate heat transfer equations in the tissue region and the blood region are simultaneously solved for different vascular models. A volumetric heat source term based on Beer–Lambert law is introduced into the energy equation to account for laser heating. The heating pattern is taken to depend on the absorption and scattering coefficients of the tissue medium. Experiments are also conducted on tissue mimics in the presence and absence of simulated blood vessels to validate the numerical model. The coupled heat transfer between thermally significant blood vessels and their surrounding tissue for three different tissue-vascular networks are analyzed keeping the laser irradiation constant. A surface temperature map is obtained for different vascular models and for the bare tissue (without blood vessels). The transient temperature distribution is seen to differ according to the nature of the vascular network, blood vessel size, flow rate, laser spot size, laser power and tissue blood perfusion rate. The simulations suggest that the blood flow through large blood vessels in the vicinity of the photothermally heated tissue can lead to inefficient heating of the target.     

Two-regime model of the perfusion measuring heated thermocouple probe

A theoretical analysis of the transient temperature responses of a heated thermocouple and its surroundingin vivo tissue is described. The model includes the effects of local blood perfusion, metabolic heat generation and blood pooling. The solutions presented are generalized for pulsed heating in the probe region. Inspection of these solutions reveals that for accurate experimental results precise knowledge of the tissue's thermal conductivity is necessary but that blood pooling around the probe may sometimes be regarded as an insignificant parameter.     

Heat transfer analysis of skin during thermal therapy using thermal wave equation

Specifying exact geometry of vessel network and its effect on temperature distribution in living tissues is one of the most complicated problems of the bioheat field. In this paper, the effects of blood vessels on temperature distribution in a skin tissue subjected to various thermal therapy conditions are investigated. Present model consists of counter-current multilevel vessel network embedded in a three-dimensional triple-layered skin structure. Branching angles of vessels are calculated using the physiological principle of minimum work. Length and diameter ratios are specified using length doubling rule and Cube law, respectively. By solving continuity, momentum and energy equations for blood flow and Pennes and modified Pennes bioheat equations for the tissue, temperature distributions in the tissue are measured. Effects of considering modified Pennes bioheat equation are investigated, comprehensively. It is also observed that blood has an impressive role in temperature distribution of the tissue, especially at high temperatures. The effects of different parameters such as boundary conditions, relaxation time, thermal properties of skin, metabolism and pulse heat flux on temperature distribution are investigated. Tremendous effect of boundary condition type at the lower boundary is noted. It seems that neither insulation nor constant temperature at this boundary can completely describe the real physical phenomena. It is expected that real temperature at the lower levels is somewhat between two predicted values. The effect of temperature on the thermal properties of skin tissue is considered. It is shown that considering temperature dependent values for thermal conductivity is important in the temperature distribution estimation of skin tissue; however, the effect of temperature dependent values for specific heat capacity is negligible. It is seen that considering modified Pennes equation in processes with high heat flux during low times is significant.     

Effect of Several Environmental Conditions on the “Thermal Death Rate” of Endospores of Aerobic, Thermophilic Bacteria

The composition of the recovery medium affected the apparent heat resistance of Bacillus stearothermophilus when the pH of the medium was 7.0 but not when the pH was 6.5. The rate of thermal death at 110 C was exponential. Deviations from exponential rates of thermal death during the initial phases of heating at 96 C were observed with endospores of B. coagulans under different conditions of sporulation. Additionally, the apparent heat resistance was influenced by the composition of the media used for sporulation and recovery and by the composition of the suspending menstruum. The presence of 0.001 m sorbic acid in the suspending menstruum at pH 7.0 and the temperature of incubation of the cultures after heating did not affect the apparent heat resistance of B. coagulans. Several explanations are discussed for the observed deviations from exponential thermal death rates and the effect of the environment on the apparent heat resistance of B. coagulans.     

Skin blood flow influences near-infrared spectroscopy-derived measurements of tissue oxygenation during heat stress.

Near-infrared (NIR) spectroscopy is a noninvasive optical technique that is increasingly used to assess muscle oxygenation during exercise with the assumption that the contribution of skin blood flow to the NIR signal is minor or nonexistent. We tested this assumption in humans by monitoring forearm tissue oxygenation during selective cutaneous vasodilation induced by locally applied heat (n = 6) or indirect whole body heating (i.e., heating subject but not area surrounding NIR probes; n = 8). Neither perturbation has been shown to cause a measurable change in muscle blood flow or metabolism. Local heating (approximately 41 degrees C) caused large increases in the NIR-derived tissue oxygenation signal [before heating = 0.82 +/- 0.89 optical density (OD), after heating = 18.21 +/- 2.44 OD; P < 0.001]. Similarly, whole body heating (increase internal temperature 0.9 degrees C) also caused large increases in the tissue oxygenation signal (before heating = -0.31 +/- 1.47 OD, after heating = 12.48 +/- 1.82 OD; P < 0.001). These increases in the tissue oxygenation signal were closely correlated with increases in skin blood flow during both local heating (mean r = 0.95 +/- 0.02) and whole body heating (mean r = 0.89 +/- 0.04). These data suggest that the contribution of skin blood flow to NIR measurements of tissue oxygenation can be significant, potentially confounding interpretation of the NIR-derived signal during conditions where both skin and muscle blood flows are elevated concomitantly (e.g., high-intensity and/or prolonged exercise).     

A parametric study of thermal therapy of skin tissue

A thermal therapy for cancer in skin tissue is numerically investigated using three bioheat conduction models, namely Pennes, thermal wave and dual-phase lag models. A laser is applied at the surface of the skin for cancer ablation, and the temperature and thermal damage distributions are predicted using the three bioheat models and two different modeling approaches of the laser effect. The first one is a prescribed surface heat flux, in which the tissue is assumed to be highly absorbent, while the second approach is a volumetric heat source, which is reasonable if the scattering and absorption skin effects are of similar magnitude. The finite volume method is applied to solve the governing bioheat equation. A parametric study is carried out to ascertain the effects of the thermophysical properties of the cancer on the thermal damage. The temperature distributions predicted by the three models exhibit significant differences, even though the temperature distributions are similar when the laser is turned off. The type of bioheat model has more influence on the predicted thermal damage than the type of modeling approach used for the laser. The phase lags of heat flux and temperature gradient have an important influence on the results, as well as the thermal conductivity of the cancer. In contrast, the uncertainty in the specific heat and blood perfusion rate has a minor influence on the thermal damage.     

Determination of the 3D temperature distribution during ferromagnetic hyperthermia under the influence of blood flow

A numerical simulation of tissue heating during thermo-seed ferromagnetic hyperthermia was performed to determine the temperature distribution of treated tumor tissues under the influence of three large blood vessels at different locations. The effects of the blood velocity waveform, blood vessel size, Curie point of the thermo-seeds and the thermo-seed number on temperature distributions were analyzed. The results indicate that the existence of a blood vessel inside the tumor has a significant cooling effect on the temperature distribution in a treated tumor tissue, which is enhanced with an increase in blood velocity. However, the pulsatile blood flow does not have apparently different effects on the outcomes of uniformly heating target tissues in comparison with the steady blood flow during the hyperthermia process. It is also concluded that a higher Curie point temperature and an increase in the number of thermo-seeds can result in profound increases in the temperature variations of the tumor tissue. In addition, tissue-equivalent phantom experiments were conducted to confirm the cooling effects of the blood vessels, and to validate the effectiveness and accuracy of the proposed heat transfer model for the ferromagnetic hyperthermia.     

Uncertainty analysis for temperature prediction of biological bodies subject to randomly spatial heating

An analytical solution to the Pennes bioheat transfer equation in three-dimensional geometry with practical hyperthermia boundary conditions and random heating was obtained in this paper. Uncertainties for the predicted temperatures of tissues due to approximate parameters were studied based on analyzing one-dimensional heat transfer in the biological bodies subject to a spatially decay heating. Contributions from each of the thermal parameters such as heat conductivity, blood perfusion rate, and metabolic rate of the tissues, the scattering coefficient and the surface power flux of the heating apparatus were compared and the uncertainty limit for temperature distribution in this case was estimated. The results are useful in a variety of clinical hyperthermia and biological thermal parameter measurement.     

Comparative evaluation of hyperthermia heating modalities. I. Numerical analysis of thermal dosimetry bracketing cases

A method for comparing the relative abilities of different hyperthermia heating modalities to properly heat tumors has been developed using solutions of the bio-heat transfer equation. A single measure, the range of absorbed powers that gives acceptable tissue temperature distributions, is used to characterize the ability of a given heating technique to heat a given tumor. An acceptable tissue temperature distribution is one for which (a) the temperatures in the coolest regions of the tumor are above a minimum therapeutic value, (b) the temperatures in the hottest regions of the tumor do not exceed a maximum clinically acceptable value, and (c) the normal tissue temperatures do not exceed maximum clinically acceptable levels. This measure can be interpreted directly in clinical terms as the range of power settings on the power indicator of a heating device for which acceptable tumor heatings will occur. This paper describes the basis of the method and investigates the role of tumor blood perfusion patterns in determining the size of the acceptable power range. Three tumor perfusion patterns are investigated: uniform tumor perfusion, a concentric annulli perfusion model in which the tumor consists of a necrotic core surrounded by two concentric layers of increased perfusion, and a random perfusion distribution model. The results show that, in general, the uniform and annular perfusion models serve as bracketing case patterns. That is, they give acceptable power range values that are upper and lower limits of the acceptable power ranges obtained for the random perfusion patterns. The method is applied to heating patterns that simulate those obtained from a variety of different available heating techniques, and it is found to be valid for all cases studied. The role of normal tissue limiting conditions is also investigated.     

Laser-induced heating of dextran-coated mesocapsules containing indocyanine green

Indocyanine green (ICG) is a photosensitive reagent with clinically relevant diagnostic and therapeutic applications. Recently, ICG has been investigated for its utility as an exogenous chromophore during laser-induced heating. However, ICG's effectiveness remains hindered by its molecular instability, rapid circulation kinetics, and nonspecific systemic distribution. To overcome these limitations, we have encapsulated ICG within dextran-coated mesocapsules (MCs). Our objective in this study was to explore the ability of MCs to induce thermal damage in response to laser irradiation. To simulate tumorous tissue targeted with MCs, cylindrical phantoms were prepared consisting of gelatin, intralipid emulsion, and various concentrations of MCs. The phantoms were embedded within fresh chicken breast tissue representing surrounding normal tissue. The tissue models were irradiated at lambda = 808 nm for 10 min at constant power (P = 4.2 W). Five hypodermic thermocouples were used to record the temperature at various depths below the tissue surface and transverse distances from the laser beam central axis during irradiation. Temperature profiles were processed to remove the baseline temperature and influence of light absorption by the thermocouple and subsequently used to calculate a damage index based on the Arrhenius damage integral. Tissue models containing MCs experienced a maximum temperature change of 18.5 degrees C. Damage index calculations showed that the heat generation from MCs at these parameters is sufficient to induce thermal damage, while no damage was predicted in the absence of MCs. ICG maintains its heat-generating capabilities in response to NIR laser irradiation when encapsulated within MCs. Such encapsulation provides a potentially useful methodology for laser-induced therapeutic strategies.     

Local heating of human skin by millimeter waves: effect of blood flow

We investigated the influence of blood perfusion on local heating of the forearm and middle finger skin following 42.25 GHz exposure with an open ended waveguide (WG) and with a YAV mm wave therapeutic device. Both sources had bell-shaped distributions of the incident power density (IPD) with peak intensities of 208 and 55 mW/cm(2), respectively. Blood perfusion was changed in two ways: by blood flow occlusion and by externally applied vasodilator (nonivamide/nicoboxil) cream to the skin. For thermal modeling, we used the bioheat transfer equation (BHTE) and the hybrid bioheat equation (HBHE) which combines the BHTE and the scalar effective thermal conductivity equation (ETCE). Under normal conditions with the 208 mW/cm(2) exposure, the cutaneous temperature elevation (DeltaT) in the finger (2.5 +/- 0.3 degrees C) having higher blood flow was notably smaller than the cutaneous DeltaT in the forearm (4.7 +/- 0.4 degrees C). However, heating of the forearm and finger skin with blood flow occluded was the same, indicating that the thermal conductivity of tissue in the absence of blood flow at both locations was also the same. The BHTE accurately predicted local hyperthermia in the forearm only at low blood flow. The HBHE made accurate predictions at both low and high perfusion rates. The relationship between blood flow and the effective thermal conductivity (k(eff)) was found to be linear. The heat dissipating effect of higher perfusion was mostly due to an apparent increase in k(eff). It was shown that mm wave exposure could result in steady state heating of tissue layers located much deeper than the penetration depth (0.56 mm). The surface DeltaT and heat penetration into tissue increased with enlarging the irradiating beam area and with increasing exposure duration. Thus, mm waves at sufficient intensities could thermally affect thermo-sensitive structures located in the skin and underlying tissue.     

Studies on the three-dimensional temperature transients in the canine prostate during transurethral microwave thermal therapy

Thermal therapy of benign prostatic hyperplasia requires accurate prediction of the temperature distribution induced by the heating within the prostatic tissue. In this study, the Pennes bioheat transfer equation was used to model the transient heat transfer inside the canine prostate during transurethral microwave thermal therapy. Incorporating the specific absorption rate of microwave energy in tissue, a closed-form analytical solution was obtained. Good agreement was found between the theoretical predictions and in-vivo experimental results. Effects of blood perfusion and the cooling at the urethral wall on the temperature rise were investigated within the prostate during heating. The peak intraprostatic temperatures attained by application of 5, 10, or 15 W microwave power were predicted to be 38 degrees C, 41 degrees C, and 44 degrees C. Results from this study will help optimize the thermal dose that can be applied to target tissue during the therapy.     

Heating of tissues by microwaves: A model analysis

We consider the thermal response times for heating of tissue subject to nonionizing (microwave or infrared) radiation. The analysis is based on a dimensionless form of the bioheat equation. The thermal response is governed by two time constants: one(τ₁) pertains to heat convection by blood flow, and is of the order of 20–30 min for physiologically normal perfusion rates; the second (τ₂) characterizes heat conduction and varies as the square of a distance that characterizes the spatial extent of the heating. Two idealized cases are examined. The first is a tissue block with an insulated surface, subject to irradiation with an exponentially decreasing specific absorption rate, which models a large surface area of tissue exposed to microwaves. The second is a hemispherical region of tissue exposed at a spatially uniform specific absorption rate, which models localized exposure. In both cases, the steady-state temperature increase can be written as the product of the incident power density and an effective time constant τ_eff, which is defined for each geometry as an appropriate function of τ₁ and τ₂. In appropriate limits of the ratio of these time constants, the local temperature rise is dominated by conductive or convective heat transport. Predictions of the block model agree well with recent data for the thresholds for perception of warmth or pain from exposure to microwave energy. Using these concepts, we developed a thermal averaging time that might be used in standards for human exposure to microwave radiation, to limit the temperature rise in tissue from radiation by pulsed sources. We compare the ANSI exposure standards for microwaves and infrared laser radiation with respect to the maximal increase in tissue temperature that would be allowed at the maximal permissible exposures. A historical appendix presents the origin of the 6-min averaging time used in the microwave standard. Bioelectromagnetics 19:420–428, 1998. © 1998 Wiley-Liss, Inc.     

Simultaneous measurements of local tissue temperature and blood perfusion rate in the canine prostate during radio frequency thermal therapy

Local tissue temperature and blood perfusion rate were measured simultaneously to study thermoregulation in the canine prostate during transurethral radio-frequency (RF) thermal therapy. Thermistor bead microprobes measured interstitial temperatures and a thermal clearance method measured the prostatic blood perfusion rate under both normal and hyperthermic conditions. Increase in local tissue temperature induced by the RF heating increased blood perfusion throughout the entirety of most prostates. The onset of the initial increase in blood perfusion was sometimes triggered by a temporal temperature gradient at low tissue temperatures. When tissue temperature was higher than 41°C, however, the magnitude and the spatial gradient of temperature may play significant roles. It was found that the temperature elevation in response to the RF heating was closely coupled with local blood flow. The resulting decrease in or stabilization of tissue temperature suggested that blood flow might act as a negative feedback of tissue temperature in a closed control system. Results from this experiment provide insights into the regulation of local perfusion under hyperthermia. The information is important for accurate predictions of temperature during transurethral RF thermal therapy.