Issues in modeling thermal alterations in tissues.

Thermal injury in living tissues is commonly modeled as a rate process in which cell death is interpreted to occur as a function of a single kinetic process. Experimental data indicate that multiple rate processes govern the manifestation of injury and that these processes may act over a broad spectrum of time domains. Injury is typically computed as a dimensionless function (omega) of the temperature time history via an Arrhenius relationship to which numerical values are assigned based on defined threshold levels of damage. However, important issues central to calculation and interpretation of the omega function remain to be defined. These issues include the following: how is temperature identified in time and space within a tissue exposed to thermal stress; what is the biophysical and physiological meaning of a quantitative value for omega; how can omega be quantified in an experimental system; how should omega be scaled between graded levels of injury; and what are the differences in injury kinetics between unit volume- and unit surface area-governed processes of energy deposition into tissue to cause thermal stress? This paper addresses these issues with the goal of defining a more rigorous and comprehensive standard for modeling thermal injury in tissues.

Prediction of transient temperature fields and cumulative tissue destruction for radio frequency heating of a tumor.

A therapeutic hyperthermia protocol using a radio frequency (rf) electrode placed adjacent to a bronchial wall tumor has been modeled using the finite element technique. Variable physical properties and variable blood perfusion have been assigned to the tumor and to the surrounding normal lung tissue. The Laplace equation was solved on a curvilinear grid for a single rf source electrode to determine the steady-state electric field, which in turn governs the energy deposition function. The heat generation in the tumor and in the lung tissue is then calculated from the energy deposition profile, and the bioheat equation is solved on the same finite element mesh to determine the transient temperature history. The temperatures are displayed as isothermal contours at designated times during the protocol and as temperature histories at selected points. In addition, an Arrhenius-type injury model has been implemented to predict thermally induced damage, from which equal total amounts of energy are deposited into the tissue using a constant power density for an appropriate time or using a cyclic heating pattern. The cyclic heating pattern consisted of a series of equal duration time periods during which the rf current source is alternately turned on and off (50% duty cycle). This study illustrates how a finite element model could be used to evaluate alternative protocols for heating a tumor of a specific geometry and to evaluate thermally induced damage to surrounding normal tissue.

Modelling infrared temperature measurements: implications for laser irradiation and cryogen cooling studies.

The use of thermographic techniques has increased as infrared detector technology has evolved and improved. For laser-tissue interactions, thermal cameras have been used to monitor the thermal response of tissue to pulsed and continuous wave irradiation. It is important to note that the temperature indicated by the thermal camera may not be equal to the actual surface temperature. It is crucial to understand the limitations of using thermal cameras to measure temperature during laser irradiation of tissue. The goal of this study was to demonstrate the potential difference between measured and actual surface temperatures in a quantitative fashion using a ID finite difference model. Three ablation models and one cryogen spray cooling simulation were adapted from the literature, and predictions of radiometric temperature measurements were calculated. In general, (a) steep superficial temperature gradients, with a surface peak, resulted in an underestimation of the actual surface temperature, (b) steep superficial temperature gradients, with a subsurface peak, resulted in an overestimation, and (c) small gradients led to a relatively accurate temperature estimate.

Unsupervised classification of cell images using pyramid node linking.

In this communication we describe a segmentation technique which combines two properties in an iterative and hierarchial matter to correctly segment and classify the given cell images. The technique is applied to digital images taken from microscope slides of cultured rat liver cells, and the goal is to classify these cells into one of three possible classes. The first class cells (I) are morphologically normal and stain the darkest. The second class cells (II) are slightly damaged showing both nuclear and cytoplasmic swelling with resultant lessening of staining affinity. The third class cells (III) are markedly damaged as demonstrated by the presence of cytoplasmic vacuolization, or are completely disintegrated. First class cells are classified by taking advantage of their staining affinity; the original gray level image is segmented into four gray levels. The darkest is then classified as type I. Type III cells are classified by using high business as a characteristic; the standard deviation of the original image is segmented into four business levels. The highest level is classified as type III cell. Assuming only the three cell types are present in any given image, the remaining non-background unclassified pixels are determined to belong to type II cells.

Visualization of dynamic subcutaneous vasomotor response by computer-assisted thermography.

Infrared thermography is a noninvasive and nonionizing imaging modality which detects thermally significant subcutaneous blood vessels as linear heat patterns projected onto the skin surface. In clinical thermography, pseudo-colors are typically used to represent isothermal regions. However, pseudo-colors destroy the connectivity of vascular patterns since the intravenous temperature of a subcutaneous blood vessel varies along its length. This representation also confounds estimates of vessel boundary location since boundary information is rendered by temperature gradients, and not by isotherms. This paper describes two computer-assisted methodologies for the visualization of peripheral subcutaneous vasomotor events. The first approach, which utilizes a three-stage segmentation strategy based on edge detection, can visualize temperature differences of approximately 3.5 degrees C between the subcutaneous vessel boundaries and surrounding tissue. The second approach requires user interaction with an adaptive filtering algorithm that selectively enhances vascular patterns in the thermogram while decreasing background noise artifacts. The user interactively selects decision thresholds used by the algorithm to develop symbolic, axiomatic models of homogeneous and bimodal local contrast regions. The result of this trained filter is then employed in a technique called digital subtraction thermographic venography for the extraction of subcutaneous venous patterns. This second approach shows less ambiguity and higher sensitivity than the edge detection approach in resolving subtle temperature differences of approximately 1.2 degrees C between the vessel and surrounding tissue. Computer-processed frames from both of these approaches are used for the dynamic visualization of normal and pathological vasomotor responses to thermal challenges, thereby providing diagnostic visual cues which are unavailable in the original thermograms.

Changes in birefringence as markers of thermal damage in tissues.

Light microscopy using polarized transmission illumination of routinely stained histologic sections shows changes of the native birefringence of certain tissue constituents when heated by laser irradiation or electrosurgical current. The naturally occurring birefringence of cardiac muscle disappears permanently when the muscle is frozen, thawed, and heated to temperatures in excess of 42 degrees C in vitro. This loss of birefringence is produced with temperatures at which other morphologic thermal changes are hard to detect; thus, it is a low-temperature tissue marker which can be used to observe the extent of thermal damage in tissues. Partial loss of the native birefringence of collagen occurs in canine urinary bladder coagulated by laser irradiation and pericardium heated with electrodes. In addition, thermally coagulated collagens have variable birefringence color shifts when compared to the adjacent unaffected collagens in stained histologic sections. The gradual birefringence color changes are seen at tissue temperatures higher than those at which the thermally induced hyalinization (coagulation) of collagen usually occurs (about 60-70 degrees C), but below those at which carbonization is seen (200+ degrees C). Birefringence changes can be measured to test mathematical models of thermal damage necessary for development of dosimetry models in medical applications of laser irradiation.

Ability of the Lapicque and Blair strength-duration curves to fit experimentally obtained data from the dog heart.

The objective of this study was to determine the ability of the empirical Lapicque and theoretically derived Blair expressions for excitation to fit experimentally obtained threshold current values to evoke a ventricular extrasystole using rectangular-wave stimuli applied to the dog heart. The data points were fitted to both expressions and the ability of each to predict the measured values was determined. The Levenberg-Marquardt (L-M) algorithm was used to fit the Lapicque and Blair expressions. The Lapicque data were also fitted to the linear charge-duration expression of Weiss (W). It was found that the ratio of the predicted to measured current was slightly different from one 0.95 (L-M) and 1.06 (W) for the Lapicque and 0.92 (L-M) for the Blair expression. Thus, there appears to be little difference between the ability of the expressions to fit the same experimentally obtained data. The L-M Lapicque fit is best for the short durations range; the Weiss-Lapicque fit overestimates in the short duration range and underestimates near chronaxie. The L-M Blair fit is best for the short duration range and poor for the durations near the membrane time constant.

Thermographic evaluation of horses with podotrochlosis.

The distal forelimbs of 10 clinically normal horses with hair clipped on 1 limb were thermographically scanned before and after exercise. The thermal patterns, temperature distribution, and temperature changes after exercise were determined and compared with those of 8 horses with podotrochlosis. Clipping the hair did not cause changes in the thermal patterns, but the clipped limbs were warmer than the unclipped limbs. The temperature of the limbs of horses with podotrochlosis did not increase as much after exercise as did the limbs of normal horses. The failure of skin temperature increase correlated with the radiographic evidence of enlarged vascular foramina in the navicular bone. Because the failure to increase skin temperature after exercise is the result of low blood flow, the enlarged vascular foramen can be related to a state of low blood flow.

Laser applications in clinical medicine.

Laser energy sources have been used in a wide range of clinical applications over the last decade to obtain cutting, coagulation, and denaturization of tissue. The therapeutic effect depends on complex interaction among the optical and thermal properties of tissue and damage accumulation. In applications where localized white coagulum is required, there are trade-offs between continuous activation using a large spot size and repetitive pulses with a small spot size as well as between a highly scattered, deep penetration source and a highly absorbed, shallow penetration laser source. For applications involving ablation of tissue, high intensity, pulsed, shallow penetration sources have many advantages over continuously activated penetrating sources. In this article, the range of applications is reviewed with particular attention to the underlying physical phenomena that influence the choice of treatment parameters.

A proposed method for quantitative performance evaluation of electrosurgical dispersive electrodes.

The measurement of thermal performance of electrosurgical dispersive electrodes presents special problems since it is necessary to determine the spatial distribution of transient temperature fields in the presence of high-energy, high-frequency, electric fields. Contact sensors are contraindicated. high-speed video-scanning thermographic systems solve the problem and, additionally, provide a permanent record of the temperature-time history of experiments on videotape. The overall uncertainty in temperature rise determination using this method is on the order of 0.4 degrees C. This measurement approach, which has been used in experiments on human subjects, yields repeatable, quantitative determinations of the thermal performance of dispersive electrodes.

Morphological image processing techniques in thermographic imaging.

Mathematical morphology is a set algebra that defines some important new techniques in image processing. Morphological filters are closely related to order statistic and other nonlinear filters, but they are uniquely sensitive to shape. A morphological filter will preserve shapes similar to its structuring element shape while modifying dissimilar shapes. Most morphological filters are effective at removing both linear and nonlinear noise processes. However, the standard morphological operators introduce a statistical and deterministic bias to images. Fortunately, these operators exist in complementary pairs that are equally and oppositely biased. One way to alleviate the bias is to average the two complementary operators. The filters formed by such averages are the midrange filter (basic operators), the pseudomedian filter (singly compound operators) and the LOCO filter (doubly compound operators). In thermographic imaging, one often wishes to find exact temperatures or accurate isothermal contours. Therefore, techniques used to remove sensor noise and scanning artifact should not introduce bias. The LOCO filter that we have devised provides the shape control and noise suppression of morphological techniques without biasing the image. We will demonstrate the effects of different structuring element shapes on thermographic images of tissue heated by laser irradiation and electrosurgery.

Thermal damage quantification utilizing tissue birefringence color image analysis.

Decreased connective tissue or cardiac muscle birefringence in transmission polarizing microscopy is an observable measure of damaged tissue concentration. Accordingly, histologic monochrome images of thermally damaged tissue exhibiting decreased birefringence provide important information about the tissue thermal history. Thus, a damage quantification algorithm based on monochrome tissue images exhibiting decreased birefringence has been developed providing tissue damage values corresponding to estimated temperature distributions. In addition, utilizing 24-bit true color tissue images, epicardial birefringence color variations resulting from thermal exposures may also be observed. Therefore, image segmentation methods are used on the red, green, and blue color image components to isolate the epicardium, similarly allowing damage quantification on this tissue constituent.

Kinetic models of laser-tissue fusion processes.

Laser tissue fusion processes depend primarily on thermal denaturization of tissue collagen: the fibrils of apposed collagen strands apparently unravel under sufficient heat and re-entwine during the cooling phase. Excessive heating desiccates the fibers to a brittle state unsuitable for fusion while inadequate heating results in weak bonds. In all cases local heat transfer processes significantly affect, and may dominate, the thermal damage realized. Consequently, in addition to spot size power and beam activation time, the choice of laser wavelength is critically dependent on the particular vessel or tissue geometry (chiefly the thickness). We have conducted parametric studies on tissue welding laser activation protocols in transient finite difference numerical models which include tissue water vaporization processes in parallel with kinetic models of collagen and smooth muscle thermal damage. The results show the complex inter-relationship between laser parameters and tissue geometry which determines whether successful fusion may be obtained. The advantage of the numerical modeling approach is that individual physical processes may be studied singly to determine their relative importance.

A real-time multi-processor 3-D echocardiographic reconstruction system.

Real-time imaging systems involve high speed processing for a variety of algorithms. An important timing constraint in the design of a real-time reconstruction system is that each individual step must be performed at video-rate. We seek to develop a real-time system for 3-D reconstruction of cardiac structures from successive 2-D B-scan ultrasound images acquired using the Tilt Echo technique, developed by Buckey et al. This system will be used to evaluate cardiac performance parameters such as stroke volume and ventricular mass.

The effect of gelled-pad design on the performance of electrosurgical dispersive electrodes.

A two-dimensional model of a simplified configuration of the gelled-pad electrode applied to human tissue was developed. As a consequence of the boundary discontinuity near the edge of the pad, the model predicted high peripheral and low central surface temperature rises. By comparison with base conditions, increased gelled-pad area and gel electrical resistivity and decreased initial pad temperature reduce the temperature rise across the pad surface. Temperature distributions measured on the thighs of human subjects were shown to have similar characteristics to those predicted by the model. Even though three-dimensional and blood flow effects were not considered, the model is satisfactory for evaluating the effect of electrode design changes on thermal performance.

Equipment for local hyperthermia therapy of cancer.

Technology for local heat therapy of cancer is evolving rapidly at a number of technologically diverse and geographically scattered institutions and companies. No single technology is superior to others in all applications, and no single company, laboratory, or research group has all the answers. An ideal system would provide focused heating at depth in a predictable fashion, with little probability of generating undesired hot spots in normal tissues and little interference with monitoring equipment. Existing systems approximate this ideal to different degrees, depending on the anatomy and geometry of the tumor and its surrounding tissues. In the foregoing discussion the important problem of measuring temperatures in tumors and normal tissues has been slighted. At the present time, all thermometry is necessarily invasive, and there are limitations to the number of points at which temperatures can be measured utilizing percutaneously placed catheters as conduits for thermometers. However, further advances in the art, the science, and the technology of local heat therapy are likely to be forthcoming in the next few years from a diverse community of investigators and young companies who are following an interesting variety of approaches. Continued research and development in the spirit of constructive, rather than destructive, competition will certainly advance the field substantially--much to the benefit of patients. At present, however, clinical engineers should realize that hyperthermia therapy for cancer is still experimental. Despite the flurry of commercial activity, considerable caution should be exercised in the purchase and use of hyperthermia equipment.

Development of a multifrequency conductance catheter-based system to determine LV function in mice.

Transgenic mice offer a valuable way to relate gene products to phenotype, but the ability to assess the cardiovascular phenotype with pressure-volume analysis has lagged. Conductance measurement offers a method to generate an instantaneous left ventricular (LV) volume signal in the mouse but has been limited by the volume signal being a combination of blood and LV muscle. We hypothesized that by developing a mouse conductance system that operates at several simultaneous frequencies, we could identify and correct for the myocardial contribution to the instantaneous volume signal. This hypothesis is based on the assumption that mouse myocardial conductivity will vary with frequency, whereas mouse blood conductivity will not. Consistent with this hypothesis, we demonstrated that at higher excitation frequency, greater end-diastolic and end-systolic conductance are detected, as well as a smaller difference between the two. We then empirically solved for LV blood volume using two frequencies. We combined measured resistivity of mouse myocardium with an analytic approach and extracted an estimate of LV blood volume from the raw conductance signal. Development of a multifrequency catheter-based system to determine LV function could be a tool to assess cardiovascular phenotype in transgenic mice.