Nephron injury induced by diagnostic ultrasound imaging at high mechanical index with gas body contrast agent.

The right kidney of anesthetized rats was imaged with intermittent diagnostic ultrasound (1.5 MHz; 1-s trigger interval) under exposure conditions simulating those encountered in human perfusion imaging. The rats were infused intravenously with 10 microL/kg/min Definity (Bristol-Myers Squibb Medical Imaging, Inc., N. Billerica, MA, USA) while being exposed to mechanical index (MI) values of up to 1.5 for 1 min. Suprathreshold MI values ruptured glomerular capillaries, resulting in blood filling Bowman's space and proximal convoluted tubules of many nephrons. The re-establishment of a pressure gradient after hemostasis caused the uninjured portions of the glomerular capillaries to resume the production of urinary filtrate, which washed some or all of the erythrocytes out of Bowman's space and cleared blood cells from some nephrons into urine within six hours. However, many of the injured nephrons remained plugged with tightly packed red cell casts 24 h after imaging and also showed degeneration of tubular epithelium, indicative of acute tubular necrosis. The additional damage caused by the extravasated blood amplified that caused by the original cavitating gas body. Human nephrons are virtually identical to those of the rat and so it is probable that similar glomerular capillary rupture followed by transient blockage and/or epithelial degeneration will occur after clinical exposures using similar high MI intermittent imaging with gas body contrast agents. The detection of blood in postimaging urine samples using standard hematuria tests would confirm whether or not clinical protocols need to be developed to avoid this potential for iatrogenic injury.

An in vivo rat model simulating imaging of human kidney by diagnostic ultrasound with gas-body contrast agent.

One kidney of anesthetized rats was imaged by diagnostic ultrasound with contrast agent under conditions simulating both the geometry and the attenuation encountered during human perfusion imaging. Contrary to earlier predictions, glomerular capillary rupture with blood loss into Bowman's space and proximal tubules occurred in our clinically relevant model system. Quantitative analysis of histologic sections showed that 37 +/- 5% of the glomeruli at the center of the scan plane had blood cells in Bowman's space after imaging for 1 min with 1.8 MPa (mechanical index equivalent, MIe = 1.5) with a 1 s image trigger interval during IV injection of 10 microl/kg/min of Definity contrast agent (as recommended by the manufacturer). This percentage decreased rapidly with decreasing peak rarefactional pressure amplitude to an apparent threshold of 0.73 MPa (MIe = 0.6). The percentage of glomeruli with hemorrhage decreased in proportion to dose when reduced below the recommended value, but leveled-off at doses above it. The percentage of glomerular hemorrhage increased with increasing numbers of image exposures, with an initial rate of 1.1% per image. The glomerular hemorrhage also depended on the frame trigger interval with no hemorrhage evident for continuous imaging but a maximal effect for trigger intervals greater than about 1 s. These results indicated that there is a potential for clinical diagnostic ultrasound with contrast agent to induce glomerular hemorrhage.