In Vivo Gas Body Efficacy for Glomerular Capillary Hemorrhage Induced by Diagnostic Ultrasound in Rats

Glomerular capillary hemorrhage (GCH) in rat kidney provided a model for assessing in vivo gas body efficacy in diagnostic or therapeutic applications of ultrasound. Two diagnostic ultrasound machines were utilized: one monitored the harmonic B-mode contrast enhancement of the left kidney and the other exposed the right kidney for GCH production. Definity contrast agent was infused at 1, 2, 5, or 10 $\mu$L/(kg·min) and infusion durations were 30, 60, 120, or 300 s. Exposure of the right kidney was at a peak rarefactional pressure amplitude of 2.3 MPa at 1.5 MHz. The circulating dose was estimated with a simple model of agent dilution and gas body loss. For 300 s infusion at 5 $\mu$L/(kg·min), the left kidney image brightness increased to a plateau with an estimated 6.4 $\pm$ 1.3 $\mu$L/kg circulating dose with no GCH in histological sections. Exposure of the right kidney with a 1-s image interval reduced the estimated circulating dose to 1.3 $\pm$ 0.3 $\mu$ L/kg and induced 68.4% GCH. Dose and duration increases gave rapidly diminishing treatment effectiveness per gas body. The effective in vivo agent dose in rats can be reduced greatly due to high gas body destruction in the small animal, complicating predictions for similar conditions of human treatment.