Biomedical subjects

Eitan Kimmel

Publications and source records attributed to Eitan Kimmel.

10 recordsLinked to original sources

PubMed2006

Bubble growth within the skin by rectified diffusion might play a significant role in sonophoresis.

Low frequency ultrasound has successfully been used for enhancing transdermal transport of a variety of different molecules. This phenomenon is referred to as sonophoresis. Several attempts have been made to investigate the enhancing mechanism in order to modulate the overall process. In this study we assess whether rectified diffusion is a process that occurs within the skin, which could eventually lead to channeling and thereby to transdermal sonophoresis. The model presented in this paper is based on the following postulate: gas bubbles are randomly distributed within the lipid bilayers of the stratum corneum (SC). As the skin is subjected to ultrasound, gas bubbles grow by rectified diffusion. During this period, bubbles may merge with the outer or inner boundaries of the SC, or merge with neighboring bubbles. Eventually, channels are created, allowing drugs to easily penetrate through the most significant barrier to transdermal delivery, the SC. As a result, transdermal transport rate is enhanced. In this work, a mathematical model has been formulated, in which permeability enhancement of the SC is linked to channels, possibly created by means of rectified diffusion. Sonophoresis may result from various mechanisms that act in synergy. The present model predicts that rectified diffusion might be one of the factors that lead to sonophoresis during ultrasound treatment.

Algorithms↗

PubMed2006

Mitochondrial dynamics in chondrocytes and their connection to the mechanical properties of the cytoplasm.

BACKGROUND: The motion and redistribution of intracellular organelles is a fundamental process in cells. Organelle motion is a complex phenomenon that depends on a large number of variables including the shape of the organelle, the type of motors with which the organelles are associated, and the mechanical properties of the cytoplasm. This paper presents a study that characterizes the diffusive motion of mitochondria in chondrocytes seeded in agarose constructs and what this implies about the mechanical properties of the cytoplasm. METHOD OF APPROACH: Images showing mitochondrial motion in individual cells at 30 s intervals for 15 min were captured with a confocal microscope. Digital image correlation was used to quantify the motion of the mitochondria, and the mean square displacement (MSD) was calculated. Statistical tools for testing whether the characteristic motion of mitochondria varied throughout the cell were developed. Calculations based on statistical mechanics were used to establish connections between the measured MSDs and the mechanical nature of the cytoplasm. RESULTS: The average MSD of the mitochondria varied with time according to a power law with the power term greater than 1, indicating that mitochondrial motion can be viewed as a combination of diffusion and directional motion. Statistical analysis revealed that the motion of the mitochondria was not uniform throughout the cell, and that the diffusion coefficient may vary by over 50%, indicating intracellular heterogeneity. High correlations were found between movements of mitochondria when they were less than 2 microm apart. The correlation is probably due to viscoelastic properties of the cytoplasm. Theoretical analysis based on statistical mechanics suggests that directed diffusion can only occur in a material that behaves like a fluid on large time scales. CONCLUSIONS: The study shows that mitochondria in different regions of the cell experience different characteristic motions. This suggests that the cytoplasm is a heterogeneous viscoelastic material. The study provides new insight into the motion of mitochondria in chondrocytes and its connection with the mechanical properties of the cytoplasm.

Animals↗

PubMed2006

Cavitation bioeffects.

Acoustic cavitation takes place when tiny gas bubbles oscillate, grow, and collapse in liquid under the influence of ultrasonic field. This study reviews cavitation bioeffects that are found both in vivo and in vitro when exposed to either low- or high-power acoustics. Proposed mechanisms are discussed here as well based on theoretical studies, simulations and test bench experiments. Bioeffects are induced in living tissue once the gas bubble is, for instance, within a blood vessel in close vicinity to the endothelium or to the red blood cells. Conditions for inducing various bioeffects are discussed - from severe damage, such as cell necrosis, to delicate alterations, such as increased permeability of cell membrane. Present and potential applications for therapeutic purpose from stone pulverization and tissue ablation to gene transfection and transdermal delivery are reviewed including the growing use of artificial microbubbles.

Acoustics↗

PubMed2005

Stability of an encapsulated bubble shell.

The stability of an encapsulated bubble filled with gas is studied where gas is allowed to diffuse out of the bubble. A mechanistic model that takes into account shell stiffness and surface tension is considered. A critical shell radius for loss of mechanical stability is derived based on a technique adapted for small radius, where surface tension effects become substantial. A new parameter is defined that determines the relative importance of surface tension forces and shell stiffness for shell stability. The developed technique allows to predict, for a given bubble population and gas saturation level of the surrounding liquid, a range of bubble sizes which may collapse in time. Surface tension effects are dominant in determining the critical radius but have a negligible effect on the minimal radius for collapse. The influence of the surface tension on the stability of the shell is illustrated for Optison, a typical ultrasound contrast agent.

Computer Simulation↗

PubMed2005

Time and pressure dependence of acoustic signals radiated from microbubbles.

Encapsulated microbubbles are considered to be microsensors for in vivo blood pressure measurements in the cardiovascular system. To study the potential of this method, we developed a simulation and an experimental set-up that relate various characteristics of radiated acoustic signals from the microbubbles to the varying ambient pressure. Both the simulation and the experiment show that the radiated pressure from microbubbles generates a significant subharmonic component, which is modulated by changes in the ambient pressure. A time-dependent decrease of the steady-state radii within a population of microbubbles causes a phase reversal phenomenon, which explains the observed time delay in the build-up of the subharmonic modulation response. Additionally, we identify a frequency-capturing effect that indicates the termination of the nonlinear behavior of the microbubbles. Our research suggests that these subharmonic signals can be used for in vivo blood pressure measurements and highlights some of the considerations that need to be addressed in developing such techniques.

Albumins↗

PubMed2004

Enhancement of antigen uptake and antibody production in goldfish (Carassius auratus) following bath immunization and ultrasound treatment.

Ultrasound irradiation and hyperosmotic treatments were compared as facilitators of antigen (BSA) penetration through the skin by bath vaccination and as enhancers of the antibody response in goldfish. The kinetics of BSA penetration and accumulation into the skin, and via it to the blood, and the consequent specific stimulation of the humoral immune response, were studied. The main findings are: (1). ultrasonic treatment is more effective than hyperosmotic treatment in enhancing both antigen transport through the skin and antibody production; (2). the requirements for high antigen concentrations, which are needed for simple bath immersion, could be reduced five times in presonicated fish; and (3). anesthesia, which significantly reduced gill uptake following hyperosmotic treatment, had no effect on skin uptake. The importance of these finding for mass vaccination of adult fish and larvae is discussed.

Animals↗

PubMed2004

Ultrasound attenuation by encapsulated microbubbles: time and pressure effects.

Ultrasound (US) contrast agents (UCA) consist of artificial encapsulated microbubbles filled with low-diffusivity gas. This study evaluated, both experimentally and theoretically, the behavior of a cloud of encapsulated microbubbles while the surrounding pressure was modified within the physiological range. The theoretical analysis included calculation of US attenuation caused by a bubble cloud. The radius and gas content of each bubble were determined from a solution of a diffusion problem. Shell permeability and rigidity were taken into account. Both experiments and theory demonstrated that, for fixed ambient pressures, higher pressures result in increased rate of attenuation decay. Pulsatile ambient pressure induces pulsations of attenuation of the same frequency. In general, theoretical predictions are in good agreement with experimental data.

Acoustics↗

PubMed2004

Shear stress induced by a gas bubble pulsating in an ultrasonic field near a wall.

Some of the effects that therapeutic ultrasound has in medicine and biology may be associated with steady oscillations of gas bubbles in liquid, very close to tissue surface. The bubble oscillations induce on the surface steady shear stress attributed to microstreaming. A mathematical simulation of the problem for both free and capsulated bubbles, known as contrast agents, is presented here. The simulation is based on a solution of Laplace's equation for potential flow and existing models for microstreaming. The solution for potential flow was obtained numerically using a boundary integral method. The solution provides the evolution of the bubble shape, the distribution of the velocity potential on the surface, and the shear stress along the surface. The simulation shows that significant shear stresses develop on the surface when the bubble bounces near the tissue surface. In this case, pressure amplitude of 20 kPa generates maximal steady shear stress of several kilo Pascal. Substantial shear stress on the tissue surface takes place inside a circular zone with a radius about half of the bubble radius. The predicted shear stress is greater than stress that causes hemolysis in blood and several orders of magnitude greater than the physiological stress induced on the vessel wall by the flowing blood.

Algorithms↗

PubMed2003

Constant and variable stiffness and damping of the leg joints in human hopping.

The present study deals with the stiffness and damping profiles of the leg joints during the ground-contact phase of hopping. A two-dimensional (sagittal plane) jumping model, consisting of four linked rigid segments and including the paired feet, shanks, thighs, and the head-arms-trunk segment, was developed. The segments were interconnected by damped torsional springs, representing the action of the muscles, tendons and ligaments across the joint and of the other joint tissues. A regressive function was used to express stiffness and damping, and included second-order dependence on angle and first-order dependence on angular velocity. By eliminating redundancies in the numerical solution using multicollinearity diagnostic algorithms, the model results revealed that the correct and sufficient nonlinearity for the joint stiffness is of the first order. Damping was found negligible. The stiffness profiles obtained were bell-shaped with a maximum near midstance and nonzero edge values. In predicting the joint moments, the obtained variable joint stiffnesses provided a closer agreement compared to a constant stiffness model. The maximal stiffness was found to be in linear correlation with the initial stiffness in each joint, providing support to the of muscles' preactivation strategy during the flight phase of hopping. All stiffnesses increased with increasing hopping frequency. The model presented provides an effective tool for future designing of artificial legs and robots and for the development of more accurate control strategies.

Adult↗

PubMed2002

A blood vessel exposed to ultrasound: a mathematical simulation of the temperature field.

In this article we present a mathematical simulation of the temperature field in and around a blood vessel when it is sonicated by a focused ultrasound beam. A simplified geometry is considered: a cylindrical blood vessel is embedded in tissue parallel to a flat skin surface. The ultrasound transducer is placed on the skin above the blood vessel, perpendicular to the skin surface. The 3D geometry of the problem is simplified by transformation, which maps the domain into a parallelepiped. A computational algorithm and computer program were developed. The simulation provides the conditions for successful occlusion of a blood vessel and demonstrates the significant role of the blood flow rate on the temperature difference between the vessel wall and the surrounding tissue. Comparing the predictions with published experimental data tested the validity of the method.

Blood Flow Velocity↗