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Biomedical subjects

R L Levin

Publications and source records attributed to R L Levin.

36 records · Page 2Linked to original sources

Improved stop-flow apparatus to measure permeability of human red cells and ghosts.

An improved stop-flow apparatus has been designed and constructed to measure the permeability characteristics of human red cells, which can be inferred from the time course of red cell volume changes following a sudden change in cellular environment produced by a raped mixing device. The improved apparatus is directly coupled to a computer which automates the subtraction and averaging procedures that have been developed to minimize the noise generated in the system by the cessation of red cell forward motion when the flow is suddenly stopped. Real time data acquisition also makes it possible to increase the number of data points by an order of magnitude, thus improving accuracy significantly. The apparatus has been tested by measurements of the human red cell hydraulic permeability coefficient. Data are presented to validate the subtraction procedure. Experiments have also been carried out on red cell ghosts which indicate that the hydraulic conductivity of the ghost is similar to that of the undisturbed red cell.

Adult↗

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↗

Effect of solution non-ideality on erythrocyte volume regulation.

A non-ideal, hydrated, non-dilute pseudo-binary salt-protein-water solution model of the erythrocyte intracellular solution is presented to describe the osmotic behavior of human erythrocytes. Existing experimental activity data for salts and proteins in aqueous solutions are used to formulate van Laar type expressions for the solvent and solute activity coefficients. Reasonable estimates can therefore be made of the non-ideality of the erythrocyte intracellular solution over a wide range of osmolalities. Solution non-ideality is shown to affect significantly the degree of solute polarization within the erythrocyte intracellular solution during freezing. However, the non-ideality has very little effect upon the amount of water retained within erythrocytes cooled at sub-zero temperatures.

Biophysical Phenomena↗

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↗

Correspondence of closest gradient voxels--a robust registration algorithm.

A robust, automatic volume registration algorithm based on intensity gradients is presented. This algorithm can successfully perform registrations under conditions of unrelated intervolume voxel intensities, significant object displacements, and/or significant amounts of missing data. It also allows the user to visualize the registration convergence, clearly illustrating any source of registration errors. This algorithm consists of a matching algorithm based on iteratively finding the correspondence of the closest voxels containing a high three-dimensional intensity gradient magnitude. This algorithm was tested by registering T2-weighted MR volumes that had undergone varying displacement transformations to simultaneously acquired proton-density volumes. These transformations involved rotations of up to 25 degrees followed by translations of up to 25 mm along the axis of rotation. For all registrations, the mean registration error was less than one-fifth of a voxel and the mean registration time was less than 30 minutes. In conclusion, this algorithm is shown to be a powerful method of sequence-independent MR volume registration that is simple to both use and understand.

Algorithms↗

Analysis of interpolation effects in the reslicing of functional MR images.

PURPOSE: Typically, the final step in volume registration is the reslicing of the volume of interest. The purpose of this work is to examine the effects of this reslicing on functional MRI (fMRI) data using different interpolation methods. METHOD: Functional whole-brain echo planar imaging (EPI) volumes were resliced using six different interpolation methods: trilinear, tricubic splines, and a 3D sinc function using a rectangular and a Hanning window, both with half-window lengths of 3 and 4 voxels. RESULTS: Interpolation by tricubic spline and 3D sinc using a Hanning window had comparable errors, although tricubic spline interpolation was computationally the fastest. Interpolation by trilinear and 3D sinc using a rectangular window had relatively large errors, although the speed of trilinear makes it desirable for some applications. CONCLUSION: Interpolations using all of the tested methods adversely affected the fMRI data, although these effects differed for each method.

Algorithms↗

Human leg heating using a mini-annular phased array.

The energy deposition pattern within an isolated human leg heated with a mini-annular phased array (MAPA) hyperthermia applicator has been determined. The non-tumor-bearing lower portion of a human leg amputated at the hip due to the presence of a large tumor in the thigh was "fixed" in a 50% ethanol in 0.9% saline solution. Subsequent to this fixation process, the leg was rehydrated in 0.9% saline and heated four times using a MAPA operating at 122 MHz. Specific absorption rates and electric field strengths were calculated from the rates of change of temperature with time measured at 143 different anatomical locations within the leg. When the leg was coaxial with the MAPA and the MAPA was axially positioned midway between the knee and the ankle, the points of maximum heating were skewed away from the center of the MAPA, towards the ankle of the leg and along the central axis of the MAPA. Significant temperature rise was measured inside the bone and the fat as well as inside the muscle of the leg. Bone heating was reduced when the leg was shifted away from the MAPA axis.

Amputation, Surgical↗

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↗

Hyperthermia system combined with a magnetic resonance imaging unit.

Magnetic resonance imaging (MRI) has recently been proposed as a method to monitor, noninvasively, temperature, blood flow, and cell metabolism during oncologic hyperthermia (HT). To heat and "image" simultaneously, it is necessary to combine a HT device and a MRI unit. As a demonstrative example of the problems associated with implementing such a system, a mini-annular phased array hyperthermia applicator was combined with a 0.5-T whole body MRI unit. With the aid of filters, baluns, and switches, the HT applicator and the MRI unit were made compatible. The overall system was tested using a muscle-equivalent, cylindrically shaped polyacrylamide gel phantom. No interference between the HT device and the MRI unit was observed. Noninvasive temperature images, with a resolution better than 1 degree C/cm, were obtained from images of molecular diffusion recorded before and during heating.

Humans↗

On the accuracy of noninvasive thermometry using molecular diffusion magnetic resonance imaging.

Temperature measurement using magnetic resonance imaging (MRI) of water self-diffusion is investigated. Diffusion images and derived temperatures are obtained in polyacrylamide gel phantom. The temperatures measured from MRI are compared with those from temperature probes to verify their accuracy. In general, the difference between temperatures determined from MRI diffusion images over 0.3 cm3 regions of interest and from temperature probes were 0.2 degrees C. It is concluded that current MRI technology allows noninvasive temperature tomography that is comparable with invasive thermometry with respect to temperature accuracy, has spatial and time resolutions that would be useful in hyperthermic oncology.

Body Temperature↗