The Dependence of Glomerular Capillary Hemorrhage Induced by Contrast Enhanced Diagnostic Ultrasound on Microbubble Diameter

A recently proposed two-criterion model for cavitational bioeffects in tissue with microbubbles (MBs) was tested. The glomerular capillary hemorrhage bioeffect was observed in rat kidney for contrast agent MB suspensions with mean diameters of 1.6, 3.1 and 5.5 µm. A diagnostic ultrasound machine was used at 3.6 MHz and 5.5 MHz for intermittent scans at power settings 2 dB apart. Petechial hemorrhage counts scored on the surface of the kidneys, and glomeruli were scored in histology. Thresholds for the petechial hemorrhage measurements were the same for the large and medium MB suspensions but substantially higher for the small MBs. For the histology, the medium MBs gave a higher threshold than the large MBs at 5.5 MHz. The pressure amplitude thresholds are in approximate agreement with theory, and the optimum MB size counterintuitively increased for increasing ultrasound frequency, as predicted. The two-criterion model of MB-associated capillary hemorrhage is supported.