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Biomedical subjects

R L Levin

Publications and source records attributed to R L Levin.

At least 19 recordsLinked to original sources

Noninvasive temperature imaging using diffusion MRI.

Efficacy and safety considerations for cancer therapy with hyperthermia require accurate temperature measurements throughout the heated volume. We report the use of molecular diffusion, whose temperature dependence is well known. A dedicated hyperthermia applicator was built, combining a MRI gradient coil and a rf coil. Diffusion and derived temperature images were obtained with a 1 x 2 mm pixel size on a polyacrylamide gel phantom using a clinical 1.5-T whole body MRI system. Temperatures determined from these images using 1 cm2 regions of interest were found to be within 0.2 degrees C of those recorded from the thermocouples and fiber-optic probes placed inside the gel.

Body Temperature

A three-dimensional thermal and electromagnetic model of whole limb heating with a MAPA.

Previous studies by the authors have shown that if properly implemented, the Pennes assumptions can be applied to quantify bioheat transfer during extremity heating. Given its relative numerical simplicity and its ability to predict temperatures in thermoregulated tissue, the Pennes model of bioheat transfer was utilized in a three-dimensional thermal model of limb heating. While the arterial blood temperature was assumed to be radially uniform within a cross section of the limb, axial gradients in the arterial and venous blood temperatures were computed with this three-dimensional model. A realistically shaped, three-dimensional finite element model of a tumor-bearing human lower leg was constructed and was "attached" mathematically to the whole body thermal model of man described in previous studies by the authors. The central as well as local thermoregulatory feedback control mechanisms which determine blood perfusion to the various tissues and rate of evaporation by sweating were input into the limb model. In addition, the temperature of the arterial blood which feeds into the most proximal section of the lower leg was computed by the whole body thermal model. The variations in the shape of the tissues which comprise the limb were obtained from computerized tomography scans. Axial variations in the energy deposition patterns along the length of the limb exposed to a miniannular phased array (MAPA) applicator were also input into this model of limb heating. Results indicate that proper positioning of the limb relative to the MAPA is a significant factor in determining the effectiveness of the treatment. A patient-specific hyperthermia protocol can be designed using this coupled electromagnetic and thermal model.

Body Temperature

An evaluation of the Weinbaum-Jiji bioheat equation for normal and hyperthermic conditions.

The predictions of the simplified Weinbaum-Jiji (WJ) bioheat transfer equation in one dimension are compared to those of the complete one-dimensional three-equation model that represented the starting point for the derivation of the WJ equation, as well as results obtained using the traditional bioheat transfer equation of Pennes [6]. The WJ equation provides very good agreement with the three-equation model for vascular generations 2 to 9, which are located in the outer half of the muscle layer, where the paired vessel diameters are less than 500 microns, under basal blood flow conditions. At the same time, the Pennes equation yields a better description of heat transfer in the first generation, where the vessels' diameters are greater than 500 microns and epsilon, the vessels' normalized thermal equilibration length, is greater than 0.3. These results were obtained under both normothermic and hyperthermic conditions. A new conceptual view of the blood source term in the Pennes equation has emerged from these results. This source term, which was originally intended to represent an isotropic heat source in the capillaries, is shown to describe instead the heat transfer from the largest countercurrent microvessels to the tissue due to small vessel bleed-off. The WJ equation includes this effect, but significantly overestimates the second type of tissue heat transfer, countercurrent convective heat transfer, when epsilon greater than 0.3. Indications are that a "hybrid" model that applies the Pennes equation in the first generation (normothermic) and first two to three generations (after onset of hyperthermia) and the Weinbaum-Jiji equation in the subsequent generations would be most appropriate for simulations of bioheat transfer in perfused tissue.

Arteries

Bioheat transfer in a branching countercurrent network during hyperthermia.

A bioheat transfer model which computes the spatial variations in the arteriole, venule, and muscle temperatures in a human extremity under both resting and hyperthermic conditions is presented. This model uses the two-parameter model first proposed by Baish et al. to account for the heat exchange between tissue and the paired arterioles and venules that comprise the microcirculation. Thermoregulation of the muscle blood flow during hyperthermia is also incorporated into the model. Results show that even when the paired arteriole and venule are assumed to have equal radii, the mean temperature under both steady and transient conditions is not equal to the mean of the arteriole and venule blood temperatures. Tissue temperature profiles during hyperthermia computed with the three-equation model presented in this study are similar in shape and magnitude to those predicted by the traditional one-equation Pennes bioheat transfer model. This is due primarily to the influence of thermoregulatory mechanism in the heated muscle. The unexpected agreement is significant given the inherent relative simplicity of the traditional Pennes model. An "experimental" thermal conductivity is presented to relate the theoretical results to experimental procedures that are widely used to estimate the enhancement of conductivity by perfusion.

Arterioles

Temperature mapping with MR imaging of molecular diffusion: application to hyperthermia.

Efficacy and safety considerations for hyperthermia (HT) cancer therapy require accurate temperature measurements throughout the heated volume. Noninvasive thermometry methods have been proposed, including magnetic resonance (MR) imaging based on the temperature dependence of the relaxation time T1. However, the temperature accuracy achieved to date with T1 measurements does not fulfill the HT requirements (1 degree C/cm). The authors propose to use molecular diffusion, for which temperature dependence is well known. Molecular diffusion is more sensitive than T1 and can be determined with high accuracy with MR imaging. Diffusion and derived temperature images were obtained with a 2 X 2-mm pixel size in a polyacrylamide gel phantom heated inside the head coil of a clinical 0.5-T whole-body MR imaging system by means of a modified clinical HT device made compatible with the system. Temperatures determined from these images with 0.8-cm2 regions of interest were found to be within 0.5 degrees C of those recorded with thermocouples placed inside the gel. The utility of this method in clinical hyperthermia is enhanced by its potential to also help monitor blood perfusion.

Diffusion

Heat transfer normal to paired arterioles and venules embedded in perfused tissue during hyperthermia.

A numerical model of the heat transer normal to an arteriole-venule pair embedded in muscle tissue has been constructed. Anatomical data describing the blood vessel size, spacing, and density have been incorporated into the model. This model computes temperatures along the vessel walls as well as the temperature throughout the tissue which comprises an infinitely long Krogh cylinder around the vessel pair. Tissue temperatures were computed in the steady-state under resting conditions, while transient calculations were made under hyperthermic conditions. Results show that for both large- (1st generation) and medium-sized (5th generation) vessel pairs, the mean tissue temperature within the tissue cylinder is not equal to the mean of the arteriole and venule blood temperatures under both steady-state and transient conditions. The numerical data were reduced so that a comparison could be made with the predictions of a simple two-dimensional superposition of line sources and sinks presented by Baish et al. This comparison reveals that the superposition model accurately describes the heat transfer effects during hyperthermia, permitting subsequent incorporation of this theory into a realistic three-dimensional model of heat transfer in a whole limb during hyperthermia.

Arteries

Criteria for accurate usage of block models.

The results of block model calculations for multiple discretizations of a dielectric sphere and circular cylinder suggest that it is essential that the cells must be arranged for a best-fit of the body being modeled, the matrix elements must be reasonably accurate, and the cells must be small enough so that the pulse-function basis approximation is not blatantly unreasonable. When these criteria are approximately satisfied the remaining errors appear to be mainly due to imperfect representation of the shape of the object being modeled. It appears that the accuracy can be improved by using discretizations having cells of reduced size near the surface of the object. Geometric factors are defined which allow testing the potential accuracy of a solution without dimensioning or inverting a large matrix. Several unique procedures for discretization are also described that have the potential of partially mitigating the errors due to inaccurate representation of the shape of a scatterer.

Humans

Water permeability of yeast cells at sub-zero temperatures.

A combined cryomicroscopic-multiple nonlinear regression analysis technique has been used to determine the water permeability of the yeast cell Saccharomyces cerevisiae during freezing. The time rate of change in volume of "supercooled" yeast cells was photographically monitored using a "cryomicroscope" which is capable of controlling in a programmable manner both the temperature and the time rate of change in temperature of the cell suspension being studied. Multiple nonlinear regression analysis together with a thermodynamic model of cell water transport during freezing was then used to statistically deduce the subzero temperature dependence of the cell water permeability. The water permeability process for S. cerevisiae being cooled at subzero temperatures was found to be rate-limited by the passage of water through either the plasmalemma, the cell wall, or a combination of these two permeability barriers. The hydraulic water permeability coefficient for yeast at 20 degrees C is approximately 1--2 x 10(-13) cm3/dyne sec, if extrapolation from subzero temperatures to room temperature is permissible, while the apparent activation energy governing the permeability process at subzero temperatures is approximately 45--68 kJ/mol (11--16 kcal/mol).

Cell Compartmentation

A membrane model describing the effect of temperature on the water conductivity of erythrocyte membranes at subzero temperatures.

Thermodynamic models show that the loss of intracellular water from human erythrocytes during freezing depends heavily upon the water conductivity of the erythrocyte membrane. These calculations, which are based on the simple extrapolation of ambient conductivity data to subzero temperatures, show that more than 95% of cell water is transferable during freezing, whereas experiments show that at least 20% of cell water is retained. A study of the effects of different published values for the membrane water conductivity on cell water retained during freezing shows that this discrepancy may be a consequence of the simple extrapolation procedure. For a homogeneous membrane system, absolute reaction rate theory was used to develop a surface-limited permeation model that includes the resistance to the flow of water not only through the interior region of the membrane but also across possible rate-limiting barriers at the solution-membrane interfaces. The model shows that it is unlikely that a single rate-limiting process dominates water transport in the red cell as it is being cooled from ambient to subzero temperatures. The effective membrane conductivity at subzero temperatures could possible be much lower than a simple extrapolation of existing data would predict. With the aid of this model analytical predictions of intracellular water during freezing are more consistent with experimental observations.

Blood

Effect of hydration on the water content of human erythrocytes.

An ideal, hydrated, nondilute pseudobinary salt-protein-water solution model of the RBC intracellular solution has been developed to describe the osmotic behavior of human erythrocytes during freezing and thawing. Because of the hydration of intracellular solutes (mostly cell proteins), our analytical results predict that at least 16.65% of the isotonic cell water content will be retained within RBCs placed in hypertonic solutions. These findings are consistent not only with the experimental measurements of the amount of isotonic cell water retained within RBCs subjected to nonisotonic extracellular solutions (20-32%) but also with the experimental evidence that all of the water within RBCs is solvent water. By modeling the RBC intracellular solution as a hydrated salt-protein-water solution, no anomalous osmotic behavior is apparent.

Blood Preservation

Experimental characterization of the miniannular phased array as a hyperthermia applicator.

A series of experiments has been carried out in order to characterize a miniannular phased array applicator prior to possible clinical implementation. The energy deposition patterns over the frequency range of 100 to 200 MHz were determined in several human limb models of different complexities by measuring the electric field strength patterns. The point of maximum energy deposition within a homogeneous, muscle-equivalent cylindrical phantom positioned coaxially within the MAPA was found to be at the center of the applicator. The energy deposition patterns seem to be more uniform at the lower frequencies. Inclusion of a cylindrical bone-equivalent phantom positioned coaxially with this muscle-equivalent phantom does not seem to significantly alter the energy deposition patterns in the muscle-equivalent region. For more realistically shaped, homogeneous muscle-equivalent limb models, the resulting energy deposition patterns appear to be confined mostly to the intended treatment region. However, the point of maximum energy deposition was not at the middle of the applicator as with the cylindrical model, but shifted towards a smaller cross-sectional region. This shift in location of the point of maximum energy deposition varies with the location of the MAPA on the limb. A secondary region of high-field strength was also observed at the ankle for a MAPA centered about the knee. In this study, the energy deposition patterns appear to be significantly dependent on the shape of the model. Therefore, this factor must be taken into consideration for the proper prediction and control of the heating patterns resulting from the use of this type of applicator for clinical hyperthermia treatment.

Humans

Energy deposition patterns in an amputated human lower leg heated with a miniannular phased array.

The energy deposition patterns in both alcohol-fixed and unfixed amputated human lower legs produced by a miniannular phased array (MAPA) applicator have been determined. The nontumor bearing portions of four human legs, amputated for therapeutic purposes, were heated within the MAPA. Experimental measurements of the time rate of temperature rise at many locations inside the leg (between 125 and 150) were transformed to specific absorption rate (SAR) values at each point. A simple model was developed which predicts the axial variations in SAR inside the heated limb based upon quantitative details of the leg's geometry obtained from computerized tomography scans. The axial location of the region of maximum energy deposition was predicted by the model with a precision of approximately 1 to 2 cm. Significant time rate of temperature rise was measured inside the cortical portion of the tibia, while the temperature rise in the cancellous (marrow) portion of the tibia was negligible. The alcohol fixation process appears to have no significant effect on the energy deposition patterns within the various leg tissues.

Humans