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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

Technical solution for an interactive functional MR imaging examination: application to a physiologic interview and the study of cerebral physiology.

Studies with functional magnetic resonance (MR) imaging produce large unprocessed raw data sets in minutes. The analysis usually requires transferring of the data to an off-line workstation, and this process frequently occurs after the subject has left the MR unit. The authors describe a hardware configuration and processing software that captures whole-brain raw data files as they are being produced from the MR unit. It then performs the reconstruction, registration, and statistical analysis, and displays the results in seconds after completion of the MR image acquisition.

Brain↗

Preliminary report: double-blind, placebo-controlled study of fluoxetine in depressed alcoholics.

The selective serotonergic agonist fluoxetine has demonstrated efficacy in the treatment of depression and has possible efficacy in the treatment of nondepressed and depressed alcoholics. However, no double-blind, placebo-controlled trials with any selective serotonergic medication have been reported in patients who have both major depression and alcoholism. In this study, 21 patients with DSM-III-R diagnoses of both major depressive disorder and alcohol dependence were randomized to fluoxetine or placebo in a 12-week, double-blind, parallel group trial. The patients reported a high level of current episode (52.4%), prior episode (61.9%), and lifetime (76.2%) suicidal behavior. Total alcohol consumption during the 12-week treatment course was significantly lower in the fluoxetine group than the placebo group, after controlling for baseline differences in consumption. The fluoxetine group demonstrated a four-fold greater improvement in depressive symptoms, but this difference did not reach statistical significance in this small sample. These preliminary findings suggest that fluoxetine has potential for treating the excessive alcohol ingestion of depressed alcoholics and may have potential for treating the depressive symptoms of these patients as well.

Adolescent↗

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↗

A generalized method for the minimization of cellular osmotic stresses and strains during the introduction and removal of permeable cryoprotectants.

The successful freeze preservation of mammalian cells and tissues usually requires the presence of high concentrations of cryoprotective agents (CPAs) such as glycerol, ethylene glycol, or dimethylsulfoxide. Unfortunately, the addition of these permeable agents to cells and tissues prior to freezing and their removal after thawing has been documented to be as damaging as the freeze-thaw process itself. This damaging process has been hypothesized to result from the drastic alterations in cell size caused by the osmotic stresses usually imposed upon cells during the introduction and removal of the cryoprotectants. Consequently, on the basis of a nonequilibrium thermodynamic model for the transport of water and a permeable CPA across cell membranes, a method has been developed to minimize these potentially lethal transient changes in cell size. This method involves the simultaneous variation of both the extracellular CPA and electrolyte or osmotic extender osmolalities in a balance, prescribed manner so that both the cellular water content and the total intracellular ionic strength remain constant as the intracellular CPA osmolarity is either raised or lowered. The theoretical analysis indicates that many of the resulting protocols are practical from the clinical point of view.

Animals↗