title: Theoretical gas body pulsation in relation to empirical gas-body destabilization and to cell membrane damage thresholds.
abstract: Contrast agent gas bodies attached to phagocytic monolayer cells pulsate in response to ultrasound exposure and damage the cells above thresholds, which increase in proportion to frequency. This study considered the physical basis for the thresholds and their frequency dependence. Theory for the pulsation was evaluated using empirical pulse waveforms acquired at thresholds for 1.0, 2.25, 3.5, 5.0, 7.5, and 10 MHz. For optimum-sized gas bodies, the amplitudes calculated at the thresholds were about 11% of the initial radii. At the cell membrane damage thresholds, theoretical negative shell stresses were approximately constant with frequency at about 50 MPa. This stress appears to be sufficient to induce failure of the shell, and gas body destabilization was confirmed by increases in transmission of ultrasound pulses through the monolayer and by microscopically-observed shrinkage of the gas bodies. A model of acoustic microstreaming was used to calculate the shear stress during the pulses. The maximum shear stress increased from about 1500 to 4500 Pa from 1 to 10 MHz, sufficient for the cell membrane damage. This theoretical analysis shows that both the gas body destabilization and the cell membrane damage could be expected at similar peak rarefactional pressure amplitudes, with thresholds having the observed proportionality to frequency.
authors.affiliation: University of Michigan, Department of Radiology, Ann Arbor Michigan 48109-0553, USA. douglm@umich.edu
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Miller
authors.forename: Chunyan
authors.initials: C
authors.lastname: Dou
mesh_terms: D000418:Albumins / Q000009:adverse effects*; D002462:Cell Membrane / Q000000981:diagnostic imaging*; D002478:Cells, Cultured; D003287:Contrast Media / Q000009:adverse effects*; D005466:Fluorocarbons / Q000009:adverse effects*; D005740:Gases; D006801:Humans; D045423:Microbubbles; D008962:Models, Theoretical; D010586:Phagocytes; D033081:Shear Strength; D018617:Ultrasonography, Doppler, Pulsed / Q000009:adverse effects*
chemical_list: D000418:Albumins; D003287:Contrast Media; C099458:FS 069; D005466:Fluorocarbons; D005740:Gases