Doppler Mode Pulse Sequences Mitigate Glomerular Capillary Hemorrhage in Contrast-Aided Diagnostic Ultrasound of Rat Kidney

Glomerular capillary hemorrhage (GCH) induced in rat kidney by diagnostic ultrasound involving contrast agent destruction was characterized for different modes to explore possible mitigation strategies. Anesthetized hairless rats were scanned at 2.5 MHz in a water bath with contrast agent infused at 10 mul/kg/minute via tail vein. B mode flash echo imaging (FEI), color Doppler (CD) FEI and realtime Doppler imaging at 1 frame per second were tested, which had image pulse sequences of approximately 0.53 ms, 15.8 ms, and 83.5 ms duration, respectively. Bioeffects endpoints included grossly observed blood-filled tubules, histological evaluation of GCH, and detection of hematuria. B mode FEI for 1 minute induced GCH in 38.6plusmn17.1% of glomeruli in histology from the scan plane for a peak rarefactional pressure amplitude (RPA) of 2.6 MPa. The threshold for GCH was approximately 1.5 MPa, confirmed by 10-minute exposure with agent infusion. Paradoxically, CD mode FEI delivered many more pulses but produced less GCH (P < 0.02), and real-time Doppler mode induced only 5.3plusmn3.8% (P < 0.005). Hematuria results followed the GCH trends. These findings indicate a promising strategy, which is to use relatively slow ramp-up of pulse RPAs in agent-destroying image pulse sequences, for mitigating potential bioeffects in contrast-aided diagnostic ultrasound.