| This research has investigated the correlation of acoustic emissions with associated contrast-mediated ultrasound bio-effects.; The hypothesis that motivated this study was that during exposure with ultrasound, the cavitation occurring in tissue emits acoustical signals, which if correlated with specific bio-effects, could provide a way to monitor the potential bio-effects of exposure. A good bio-effects indicator would find immediate use in research on drug and gene delivery, and could have clinical application in avoiding bio-effects in diagnosis.; Studies conducted to test the hypothesis involved investigation of (i) the influence of pulse repetition frequency (PRF) and number of exposures on cell damage, (ii) the effect of total exposure duration and pulse-to-pulse bubble distribution on acoustic emissions and corresponding cell damage, and (iii) the translation of in vitro effects to an in situ environment.; Exposures were primarily conducted at a peak rarefactional pressure of 2 MPa, 2.25 MHz insonating frequency and pulse length of 46 cycles. PRFs of 1-, 10-, 100-, 500-, and 1000 Hz were compared. High speed photography (2000 fps) was employed for the investigation of pulse-to-pulse bubble distribution while intravital microscopy was used for in situ studies.; A strong correlation was observed between acoustic emissions and bio-effects with the availability of bubbles of resonant size serving as a key link between the two. It was observed that total exposure duration may play an important role in cell damage. Damage increased with increasing total exposure duration from 0 ms to 100 ms with a plateau at above 100 ms. These results were consistent for all studies. There is, therefore, an implication that manipulating these parameters may allow for measurement and control of the extent of bioeffects. Moreover, the correlation of acoustic emission and extravasation observed in in situ studies reveals that cumulative function of the relative integrated power spectrum (CRIPS) of the emissions may find use as a monitoring method related to tissue damage due to contrast-mediated ultrasound in vivo. |