A two-criterion model for microvascular bioeffects induced in vivo by contrast microbubbles exposed to medical ultrasound

Abstract

The mechanical index (MI) is a theoretical exposure parameter for cavitational bioeffects 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 bioeffects thresholds based on the MI typically do not concur with the frequency dependence of experimentally measured thresholds for bioeffects. For example, experimental thresholds for glomerular capillary hemorrhage in rats infused with contrast microbubbles increased approximately linearly with frequency (Miller et al. UMB 2008b; 34:1678), while 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, C 3 F 8 , or a 1:1 mixture of the two and surrounded by either blood or kidney tissue. While 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 2-criterion model.

Hepatocyte Injury Induced by Contrast‐Enhanced Diagnostic Ultrasound

“…In addition, the low microvascular impact may be due to the nature of the sinusoidal capillaries present in the liver, which are large (7–15 μm in diameter) and lined by discontinuous endothelium . Recent research indicates that the capillaries, for example, in the kidney are injured by the action of the largest microbubbles in contrast agents, and microbubble expansion sufficient to stress capillary walls is required for capillary rupture . The minimal impact on liver sinusoids may be related to the limited number of large microbubble sizes available after passage through the lungs.…”