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.     

A self-heated thermistor technique to measure effective thermal properties from the tissue surface

A microcomputer based instrument to measure effective thermal conductivity and diffusivity at the surface of a tissue has been developed. Self-heated spherical thermistors, partially embedded in an insulator, are used to simultaneously heat tissue and measure the resulting temperature rise. The temperature increase of the thermistor for a given applied power is a function of the combined thermal properties of the insulator, the thermistor, and the tissue. Once the probe is calibrated, the instrument accurately measures the thermal properties of tissue. Conductivity measurements are accurate to 2 percent and diffusivity measurements are accurate to 4 percent. A simplified bioheat equation is used which assumes the effective tissue thermal conductivity is a linear function of perfusion. Since tissue blood flow strongly affects heat transfer, the surface thermistor probe is quite sensitive to perfusion.     

Thermal pulse decay method for simultaneous measurement of local thermal conductivity and blood perfusion: a theoretical analysis

Presented here is a theoretical analysis of the recently developed thermal pulse decay (TPD) method for a simultaneous measurement of local tissue conductivity and blood perfusion rate. The paper describes the theoretical model upon which the TPD method is based and details its capabilities and limitations. The theoretical aspects that affected the development of the measurement protocol are also discussed. The performance of the method is demonstrated with an experimental example which compares the measurements of local kidney blood perfusion rates made using the TPD method with the total renal blood flow obtained coincidentally using a blood flowmeter, in an anesthetized dog.     

Procedure to estimate thermophysical and geometrical parameters of embedded cancerous lesions using thermography

Based on the fact that malignant cancerous lesions (neoplasms) develop high metabolism and use more blood supply than normal tissue, infrared thermography (IR) has become a reliable clinical technique used to indicate noninvasively the presence of cancerous diseases, e.g., skin and breast cancer. However, to diagnose cancerous diseases by IR, the technique requires procedures that explore the relationship between the neoplasm characteristics (size, blood perfusion rate and heat generated) and the resulting temperature distribution on the skin surface. In this research work the dual reciprocity boundary element method (DRBEM) has been coupled with the simulated annealing technique (SA) in a new inverse procedure, which coupled to the IR technique, is capable of estimating simultaneously geometrical and thermophysical parameters of the neoplasm. The method is of an evolutionary type, requiring random initial values for the unknown parameters and no calculations of sensitivities or search directions. In addition, the DRBEM does not require any re-meshing at each proposed solution to solve the bioheat model. The inverse procedure has been tested considering input data for simulated neoplasms of different sizes and positions in relation to the skin surface. The successful estimation of unknown neoplasm parameters validates the idea of using the SA technique and the DRBEM in the estimation of parameters. Other estimation techniques, based on genetic algorithms or sensitivity coefficients, have not been capable of obtaining a solution because the skin surface temperature difference is very small.     

激光低损伤加热疗法的理论分析

激光低损伤加热疗法将激光照射与表面冷却相结合,能实现只让病变组织细胞凝固,而体表健康组织则不受损伤,它是治疗靠近体表肿瘤的一种有希望的方法。为了进一步认识这种治疗方法,本文提出了一个适用于激光低损伤加热疗法的数值计算模型,模拟了热疗过程中的光传输和热传递,得到组织内部的瞬态温度分布。在此基础上,详细讨论了散射系数、吸收系数、各向异性系数等光学参数,激光加热功率、照射半径、表面对流换热系数等热学参数。以及血液灌注率和新陈代谢等生理参数对这种低损伤加热疗法的影响。结果发现,只要通过适当调节吸收系数、散射系数和照射功率等参数就可实现对加热区域位置和范围的控制。     

Lumped parameter thermal model for the study of vascular reactivity in the fingertip

Vascular reactivity (VR) denotes changes in volumetric blood flow in response to arterial occlusion. Current techniques to study VR rely on monitoring blood flow parameters and serve to predict the risk of future cardiovascular complications. Because tissue temperature is directly impacted by blood flow, a simplified thermal model was developed to study the alterations in fingertip temperature during arterial occlusion and subsequent reperfusion (hyperemia). This work shows that fingertip temperature variation during VR test can be used as a cost-effective alternative to blood perfusion monitoring. The model developed introduces a function to approximate the temporal alterations in blood volume during VR tests. Parametric studies are performed to analyze the effects of blood perfusion alterations, as well as any environmental contribution to fingertip temperature. Experiments were performed on eight healthy volunteers to study the thermal effect of 3 min of arterial occlusion and subsequent reperfusion (hyperemia). Fingertip temperature and heat flux were measured at the occluded and control fingers, and the finger blood perfusion was determined using venous occlusion plethysmography (VOP). The model was able to phenomenologically reproduce the experimental measurements. Significant variability was observed in the starting fingertip temperature and heat flux measurements among subjects. Difficulty in achieving thermal equilibration was observed, which indicates the important effect of initial temperature and thermal trend (i.e., vasoconstriction, vasodilatation, and oscillations).     

Human males and females body thermoregulation: Perfusion effect analysis

Skin temperature is a common physiological parameter that reflects thermal responses. Blood perfusion is an important part of the physiological processes that the human body undergoes in order to maintain homeostasis. This study focuses on the effect of perfusion on the temperature distribution in human males and females body in different thermal environment. The study has been carried out for one dimensional steady cases using finite element method. The input parameter of the model is the blood perfusion or volumetric flow rate within the tissue. The appropriate physical and physiological parameters together with suitable boundary conditions that affect the heat regulations have been incorporated in the model. The study is to have a better understanding that how does thermoregulation change in human males and females skin layered due to perfusion.     

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.     

Conventional and newly developed bioheat transport models in vascularized tissues: A review

Heat transfer in a biological system is a complex process and its analysis is difficult. Heterogeneous vascular architecture, blood flow in the complex network of arteries and veins, varying metabolic heat generation rates and dependence of tissue properties on its physiological condition contribute to this complexity. The understanding of heat transfer in human body is important for better insight of thermoregulatory mechanism and physiological conditions. Its understanding is also important for accurate prediction of thermal transport and temperature distribution during biomedical applications. During the last three decades, many attempts have been made by researchers to model the complex thermal behavior of the human body. These models, viz., blood perfusion, countercurrent, thermal phase-lag, porous-media, perturbation, radiation, etc. have their corresponding strengths and limitations. Along with their biomedical applications, this article reviews various contextual issues associated with these models. After brief discussion of early bioheat models, the newly developed bioheat models are discussed in detail. Dependence of these models on biological properties, viz., thermophysical and optical properties are also discussed.     

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.     

Numerical analysis of dynamic temperature in response to different levels of reactive hyperaemia in a three-dimensional image-based hand model

Vascular reactivity (VR) is considered as an effective index to predict the risk of cardiovascular events. A cost-effective alternative technique used to evaluate VR called digital thermal monitoring (DTM) is based on the response of finger temperature to vessel occlusion and reperfusion. In this work, a simulation has been developed to investigate hand temperature in response to vessel occlusion and perfusion. The simulation consists of image-based mesh generation and finite element analysis of blood flow and heat transfer in tissues. In order to reconstruct a real geometric model of human hand, a computer programme including automatic image processing for sequential MR data and mesh generation based on the transfinite interpolation method is developed. In the finite element analysis part, blood flow perfused in solid tissues is considered as fluid phase through porous media. Heat transfer in tissues is described by Pennes bioheat equation and blood perfusion rate is obtained from Darcy velocities. Capillary pressure, blood perfusion and temperature distribution of hand are obtained. The results reveal that fingertip temperature is strongly dependent on larger arterial pressure. This simulation is of potential to quantify the indices used for evaluating the VR in DTM test if it is integrated with the haemodynamic model of blood circulation in upper limb.     

Differentiation of Breast Cancer from Fibroadenoma with Dual-Echo Dynamic Contrast-Enhanced MRI

Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) of the breast is a routinely used imaging method which is highly sensitive for detecting breast malignancy. Specificity, though, remains suboptimal. Dynamic susceptibility contrast magnetic resonance imaging (DSC MRI), an alternative dynamic contrast imaging technique, evaluates perfusion-related parameters unique from DCE MRI. Previous work has shown that the combination of DSC MRI with DCE MRI can improve diagnostic specificity, though an additional administration of intravenous contrast is required. Dual-echo MRI can measure both T₁W DCE MRI and T₂*W DSC MRI parameters with a single contrast bolus, but has not been previously implemented in breast imaging. We have developed a dual-echo gradient-echo sequence to perform such simultaneous measurements in the breast, and use it to calculate the semi-quantitative T₁W and T₂*W related parameters such as peak enhancement ratio, time of maximal enhancement, regional blood flow, and regional blood volume in 20 malignant lesions and 10 benign fibroadenomas in 38 patients. Imaging parameters were compared to surgical or biopsy obtained tissue samples. Receiver operating characteristic (ROC) curves and area under the ROC curves were calculated for each parameter and combination of parameters. The time of maximal enhancement derived from DCE MRI had a 90% sensitivity and 69% specificity for predicting malignancy. When combined with DSC MRI derived regional blood flow and volume parameters, sensitivity remained unchanged at 90% but specificity increased to 80%. In conclusion, we show that dual-echo MRI with a single administration of contrast agent can simultaneously measure both T₁W and T₂*W related perfusion and kinetic parameters in the breast and the combination of DCE MRI and DSC MRI parameters improves the diagnostic performance of breast MRI to differentiate breast cancer from benign fibroadenomas.     

Evaluation of laser-Doppler perfusion imaging for measurement of blood flow in cortical bone.

Most techniques currently available to measure blood flow in bone are time consuming and require destruction of the tissue, but laser-Doppler technology offers a less invasive method. This study assessed the utility of laser-Doppler perfusion imaging (LDI) to measure perfusion in cortical bone. Twelve mature New Zealand White rabbits were assigned to one of three groups: normal control, constriction (norepinephrine), or dilatation (nitroprusside). The left and right medial tibiae were consecutively scanned at red (634-nm) and near-infrared (810-nm) wavelengths to examine the repeatability of LDI output. The pharmacological intervention groups were injected with the respective drug, and LDI measurements at 810 nm were obtained concurrently with colored microsphere-determined flow in all of the groups. LDI effectively quantified blood flow in cortical bone and detected physiologically induced changes in perfusion. A significant positive correlation was found between microsphere-determined flow and LDI output (r = 0.6, P < 0.05). Repeatability of consecutive LDI measurements was within 5%. The effectiveness of LDI to measure perfusion in bone suggests this method has potential for investigating the role of blood flow in bone metabolism and remodeling.     

Fast inverse prediction of the freezing front in cryosurgery

Cryosurgery has become a well-established technique for the ablation of undesirable tissues such as tumors and cancers. The motivation for this study is to improve the efficacy and safety of this technique. This study presents an inverse heat transfer method for monitoring the motion of the freezing front from a cryoprobe. With the help of a thermocouple inserted into the layer of diseased tissue, the inverse heat transfer method estimates simultaneously the blood perfusion rate and the thermal conductivities of both frozen and unfrozen tissues. This information is then fed to the Pennes bioheat equation that: (1) calculates the time-varying temperature distribution inside the layer of tissue and (2) predicts the motion of the freezing front. The effect of the most influential parameters on the inverse predictions is investigated. These parameters are (1) the initial guesses for the unknown Levenberg-Marquardt polynomial parameters of the thermo-physical properties; (2) the temperature of the cryoprobe; (3) the heat transfer coefficient of the impinging jet of liquid nitrogen; and (4) the noise on the temperature data recorded by the thermocouple probe. Results show that the proposed inverse method is a promising alternative to ultrasound and Magnetic Resonance Imaging (MRI) for monitoring the motion of the freezing front during cryosurgery. For all the cryogenic scenarios simulated, the predictions of the inverse model remain accurate and stable.     

Regional lung perfusion estimated by electrical impedance tomography in a piglet model of lung collapse

The assessment of the regional match between alveolar ventilation and perfusion in critically ill patients requires simultaneous measurements of both parameters. Ideally, assessment of lung perfusion should be performed in real-time with an imaging technology that provides, through fast acquisition of sequential images, information about the regional dynamics or regional kinetics of an appropriate tracer. We present a novel electrical impedance tomography (EIT)-based method that quantitatively estimates regional lung perfusion based on first-pass kinetics of a bolus of hypertonic saline contrast. Pulmonary blood flow was measured in six piglets during control and unilateral or bilateral lung collapse conditions. The first-pass kinetics method showed good agreement with the estimates obtained by single-photon-emission computerized tomography (SPECT). The mean difference (SPECT minus EIT) between fractional blood flow to lung areas suffering atelectasis was -0.6%, with a SD of 2.9%. This method outperformed the estimates of lung perfusion based on impedance pulsatility. In conclusion, we describe a novel method based on EIT for estimating regional lung perfusion at the bedside. In both healthy and injured lung conditions, the distribution of pulmonary blood flow as assessed by EIT agreed well with the one obtained by SPECT. The method proposed in this study has the potential to contribute to a better understanding of the behavior of regional perfusion under different lung and therapeutic conditions.     

A METHOD OF CORONARY RETROPERFUSION FOR THE TREATMENT OF ACUTE MYOCARDIAL ISCHEMIA

A method of retrograde perfusion of the myocardium has been developed in dogs. It consists of a double lumen balloon-tipped catheter inserted transvenously into the coronary sinus, with one lumen connected to a roller pump, the other to a helium counterpulsing pump. Oxygenated heparinized blood is obtained from the femoral artery and pumped continuously into the coronary sinus at a pressure of 50-75 mm Hg. The balloon is inflated during diastole, sealing the coronary sinus and promoting retrograde flow, and is deflated during systole, allowing blood drainage into the right atrium and preventing venous congestion. Thirteen anesthetized open-chest dogs were subjected to 15 minutes of proximal LAD artery occlusion and 30 minutes of diastolic coronary sinus perfusion (DCSP). The area of ischemia was mapped by means of platinum electrodes capable of simultaneously measuring myocardial tissue oxygen tension M(p)O(2)) and electrograms. Reduction of M(p)O(2) with simultaneous elevation of the ST segment on the corresponding electrogram was considered an indication of ischemia. Diastolic coronary sinus perfusion improved myocardial oxygen tension in the ischemic myocardium, reduced ST segment elevation, and tended to restore arterial blood pressure. Histologically, there was no intramyocardial hemorrhage.     

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.     

正常乳腺温度分布的有限元分析

基于正常乳腺的解剖学结构和生理学特征,建立了一个乳腺组织多维热传递模型。该模型考虑了代谢产热、血液灌注和动静脉血管与组织间热的相互作用,采用有限元分析方法求解热传导方程,数值模拟正常乳腺的稳态温度分布,着重研究血液灌注和代谢产热对正常乳腺组织温度分布的影响。研究结果可为乳腺疾病的热图像分析提供重要参考。     

Generating microbial survival curves during thermal processing in real time

AIMS: To develop a method to calculate and record theoretical microbial survival curves during thermal processing of foods and pharmaceutical products simultaneously with the changing temperature. Moreover, to demonstrate that the method can be used to calculate nonisothermal survival curves, with widely available software such as Microsoft Excel. METHODS AND RESULTS: It has been assumed that the targeted organism's isothermal survival curves are not log linear and hence, the inactivation rate in nonisothermal processes is a function of the momentary temperature and the corresponding survival ratio. This could be expressed by a difference equation, which is an approximation to the continuous rate model. The concept was tested with the isothermal survival parameters of Clostridium botulinum and Bacillus sporothermodurans spores, and Salmonella enteritidis cells, using different kinds of survival models and under temperature profiles resembling those of commercial processes. As expected, there was an excellent agreement between the curves produced by solving the differential equation of the continuous model and by the incremental method, which has been posted on the web as freeware. CONCLUSIONS: It is possible to calculate nonisothermal survival curves, in real time, with an algorithm that can be written in the language of general purpose software, to follow the inactivation of one or more targeted organisms simultaneously and to simulate microbial survival patterns under existing or planned industrial thermal processes. SIGNIFICANCE AND IMPACT OF THE STUDY: Replacement of the traditional 'F0-value', which requires the log linearity of the organism's isothermal survival curves, by the more realistic theoretical survival ratio estimate as a measure of the thermal process efficacy.     

A method for producing regional hypoglycemia in blood perfused tissue

Numerous studies have focused on the metabolic contributions of glucose and other substrates in isolated tissue preparations by examining the effects of eliminating glucose from the physiologic perfusate or bath solution. To date, however, an effective method of glucose removal from the blood supply to selected tissue in the whole animal model has not been available. We have developed a method for blood glucose removal by continuous flow dialysis. This method was used to generate isolated coronary hypoglycemia for an investigation of myocardial metabolic substrate selection during hypoperfusion in open-chest, anesthetized dogs. Arterial blood was passed through the dialysis system against an isotonic and physiologic dialysate solution prior to controlled coronary perfusion. During normal perfusion pressure (100 mmHg), with a coronary blood flow of 32 ± 4 ml/min, arterial blood glucose was reduced from 3.26 ± 0.31 to 0.54 ± 0.14 mM. When blood flow was reduced to 12 ± 3 ml/min with lower perfusion pressure (40 mmHg), dialysis reduced arterial glucose from 3.53 ± 0.36 to 0.15 ± 0.03 mM. We conclude that this is an effective method for producing regional hypoglycemia.