טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentOr Meir
SubjectLinear Mechanical Effects of Low Intensity Ultrasound
on Cells
DepartmentDepartment of Biomedical Engineering
Supervisors Professor Eitan Kimmel
Professor Dror Seliktar
Full Thesis textFull thesis text - English Version


Abstract

Therapeutic ultrasound (TUS) of low to medium intensity is known to induce alterations in structure and functioning of cells and tissue, both in vivo and in vitro. Such effects, including excitation or inhibition of action potentials, enhanced angiogenesis rate, increased membrane permeability, and changes in molecular expression, cannot be attributed in many cases to rising temperatures or the presence of gas bubbles. This study attempts to find possible alternative explanation for the cases where neither thermal effects nor cavitation mechanisms count.

Because typical wavelength of TUS is large compared with the cellular scale, the mentioned effects cannot be attributed to primary acoustical strains. We thus focus our attention on the complex and dense structure of cell cytoplasm, looking for separating forces and relative motion between intracellular elements and the structure in which they are embedded.

Relating in this work only to linear, oscillating pressure variations, it is hypothesized that relative displacements between intracellular elements of different densities might appear in cells in response to TUS. Those oscillatory displacements might induce alterations in cell structure and functioning. A linear model of a spherical object, representing a typical organelle such as the nucleus, within a homogenous viscoelastic medium that vibrates uniformly is constructed and solved. The structure in which the object is embedded is described by four different rheological models, including viscous fluid, elastic solid, and Voigt and Maxwell viscoelastic constructs.

It is found that cyclic intracellular displacements comparable with and even larger than the mean thermal fluctuations may be obtained due to TUS irradiation in conditions where the relative motion of organelles is dominated by elastic response, or where the effective viscosity of the cytoplasm is low. Resonance frequencies at which intracellular vibration of maximal amplitude is obtained are found to lie within the low TUS frequency range, i.e. tens to hundreds of kHz. Local intracellular strain on the order of 0.5% is found for 1-micrometer organelle in 10-micrometer cell under typical TUS settings. It is suggested that fatigue-like, cumulative effect underlie the transfer of the intracellular strain into biological alterations.