A Two-Criterion Model for Microvascular Bio-Effects Induced In Vivo by Contrast Microbubbles Exposed to Medical Ultrasound

The mechanical index (MI) is a theoretical exposure parameter for cavitational bio-effects of diagnostic ultrasound. The theory for the MI assumed that bubbles of all relevant sizes exist in tissue, a condition that is approximated for tissues that include a microbubble contrast agent. Therefore, the MI should allow science-based safety guidance for contrast-enhanced diagnostic ultrasound. However, theoretical predictions of bio-effects thresholds based on the MI typically do not concur with the frequency dependence of experimentally measured thresholds for bio-effects. For example, experimental thresholds for glomerular capillary hemorrhage in rats infused with contrast microbubbles increased approximately linearly with frequency, whereas the MI predicted a square root dependence. Here, cavitation thresholds were computed for linear versions of the acoustic pulses used in that study assuming bubbles containing either air, C3F8, or a 1:1 mixture of the two and surrounded by either blood or kidney tissue. Although no single threshold criterion was successful, combining results for one criterion that maximized circumferential stress in the capillary wall with another that ensured an inertial collapse produced thresholds that were consistent with experimental data. This suggests that a contrast-specific safety metric may be achieved following validation of this two-criterion model.