Kenneth R. Diller

Thermal conductivity and diffusivity of biomaterials measured with self-heated thermistors

This paper presents an experimental method to measure the thermal conductivity and thermal diffusivity of biomaterials. Self-heated thermistor probes, inserted into the tissue of interest, are used to deliver heat as well as to monitor the rate of heat removal. An empirical calibration procedure allows accurate thermal-property measurements over a wide range of tissue temperatures. Operation of the instrument in three media with known thermal properties shows the uncertainty of measurements to be about 2%. The reproducibility is 0.5% for the thermal-conductivity measurements and 2% for the thermal-diffusivity measurements. Thermal properties were measured in dog, pig, rabbit, and human tissues. The tissues included kidney, spleen, liver, brain, heart, lung, pancreas, colon cancer, and breast cancer. Thermal properties were measured for 65 separate tissue samples at 3, 10, 17, 23, 30, 37, and 45°C. The results show that the temperature coefficient of biomaterials approximates that of water.

Modeling of bioheat transfer processes at high and low temperatures

Publisher Summary Heat transfer exhibits many therapeutic applications involving either a raising or lowering of temperature. It often requires precise monitoring of the spatial distribution of thermal histories that are produced during a protocol. The ability to perform accurate analysis of the heat transfer phenomena has led to a quantitative basis for describing the broad range of bioheat transfer processes that exist and in modeling the unique features of the flow of heat in living systems. This chapter presents a general background for the previous work in bioheat transfer. It describes the evolution of modeling techniques to deal with the special problems confronting the analysis of heat transfer processes in biosystems, both in vivo and in vitro. In specific, the chapter outlines the paths that are followed in arriving at the present state-of-the-art in several important areas of bioheat transfer modeling. It addresses the techniques for the modeling of many of the most important and commonly encountered examples of heat transfer processes in living systems.

Dehydration mechanism of optical clearing in tissue

Previous studies identified various mechanisms of light scattering reduction in tissue induced by chemical agents. Our results suggest that dehydration is an important mechanism of optical clearing in collagenous and cellular tissue. Photographic and optical coherence tomography images indicate that air-immersed skin and tendon specimens become similarly transparent to glycerol-immersed specimens. Transmission electron microscopy images reveal that dehydration causes individual scattering particles such as collagen fibrils and organelles to become more densely packed, but does not significantly alter size. A heuristic particle-interaction model predicts that the scattering particle volume fraction increase can contribute substantially to optical clearing in collagenous and cellular tissue.

A cryomicroscope for the study of freezing and thawing processes in biological cells

Abstract A cryomicroscope capable of effecting controlled freezing and thawing in biological cell suspensions has been developed. A dual capability for both heating and cooling is employed in conjunction with an analog control system to provide for precise regulation of the specimen temperature between 77 °K and 310 °K at time rates of temperature change between zero and several thousand degrees centigrade per minute. The microscope can be fitted with a high speed motion picture to record the dynamics of the freezing and thawing processes in slow motion. A miniature freezing and thawing system adapted to the stage of a light microscope enables a broad spectrum of cooling and warming rates to be achieved by cooling the specimen at a constant rate with a steady flow of refrigerant fluid through the system and by simultaneously dissipating electrical energy at a variable rate in a resistance heater immersed in the fluid stream and in thermal communication with the specimen. The control system is of the analog type in which a signal generator, inverter, and integrator are used to generate a voltage representative of the desired linear temperature profile, be it for cooling or warming. This profile is continuously compared in a summing unit with the amplified output of a thermocouple monitoring the specimen temperature. The output from the summing unit, which is proportional to the difference between the generated reference temperature and the specimen temperature, is amplified in a power amplifier having the resistance heater as its load. Energy is dissipated in the heater only when the specimen temperature is lower than the reference temperature. The maximal temperature for warming processes is set by a limiting diode in the integrator, whereas the minimal temperature for cooling processes is determined by the refrigerant temperature.

Quantitative phase-contrast imaging of cells with phase-sensitive optical coherence microscopy.

We describe a method for en face phase-contrast imaging of cells with a fiber-based differential phase-contrast optical coherence microscopy system. Recorded en face images are quantitative phase-contrast maps of cells due to spatial variation of the refractive index and (or) thickness of various cellular components. Quantitative phase-contrast images of human epithelial cheek cells obtained with the fiber-based differential phase-contrast optical coherence microscopy system are presented.

A Finite Element Model of Burn Injury in Blood-Perfused Skin

The burn process resulting from the application of a hot, cylindrical source to the skin surface was modeled using the finite element technique. A rotationally symmetric 125-element mesh was defined within the tissue beneath and outlying to an applied heating disk. The disk temperature and duration of contact were varied, respectively, between 50 and 100 degrees C for up to 30 s. Natural convection with ambient air was assumed for areas of skin surface not in direct contact with the disk. The simulated thermal history was used in a damage integral model to calculate the extent and severity of injury in the radial and axial dimensions.

Thermally induced injury and heat-shock protein expression in cells and tissues

Abstract: Heat‐shock proteins (HSPs) are critical components of a cells defense mechanism against injury associated with adverse stresses. Initiating insults, such as elevated or depressed temperature, diminished oxygen, and pressure, increase HSP expression and can protect cells against subsequent, otherwise lethal, insults. Although HSPs are very beneficial to the normal cell, cancer cells can also use HSPs in response to stresses associated with various therapies (hyperthermia, chemotherapy, radiation), mitigating injury incurred by these treatments. Hyperthermia is a common treatment option for prostate cancer. HSPs can be induced in regions of the tumor where temperatures are insufficient to cause lethal thermal necrosis. Elevated HSP expression can enhance tumor cell viability and impart increased resistance to subsequent chemotherapy and radiation treatments, thereby promoting tumor recurrence. An understanding of the structure, function, and thermally stimulated HSP kinetics and cell injury for prostate cancer cells is essential to designing effective hyperthermia protocols. Measured thermally induced cellular HSP expression and injury data can be employed to develop a treatment planning model for optimization of the tissue response to therapy based on accurate prediction of the HSP expression and cell damage distribution.

Quantitative low temperature optical microscopy of biological systems

A comprehensive review is presented of low temperature optical microscopy techniques as applied to the study of freezing processes in biological systems. Emphasis is placed on analysis of physical and physiological parameters which were measured and/or controlled and the procedures for effecting such operations. Quantitative analysis of photomicrographs by digital computer processing is also discussed.

Intracellular freezing: Effect of extracellular supercooling

Human erythrocytes were frozen on the stage of a cryomicroscope at accurately controlled constant-cooling rates with varying degrees of extracellular supercooling. The formation of intracellular ice was detected by direct observation of the frozen cells through the microscope. A significant coupling effect was determined between the minimum cooling rate necessary to produce intracellular freezing and the extent of supercooling. Increased degrees of extracellular supercooling reduced the range of cooling rates for which water would freeze within the cell. Specific data points were obtained at ΔTSC = 0, −5, and −12 °C for which the corresponding transition cooling rates were respectively −845, −800, and −11 °C/min. An explanation for the occurrence of this phenomenon is presented based on the physiochemical processes that govern the freezing of a cell suspension.

Issues in modeling thermal alterations in tissues.

ABSTRACT: 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 (Ω) 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 Ω 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 Ω; how can Ω be quantified in an experimental system; how should Ω 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.