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An ultrasound system has been developed to generate microbubbles in vivo for use as ultrasound contrast agent. Possible application include diagnosis of reflux in the urinary tract. In experiments designed to elucidate the contrast microbubble generation process, acoustic bursts (at 1.8 MHz, 125 ms) were propagated through a latex rubber balloon, modeled after a rabbit urinary bladder, containing fluids of various air and carbon dioxide saturations and concentrations of cavitation nuclei (0.198-micron-diam polystyrene particles). The peak rarefactional pressure threshold for contrast microbubble generation, as visualized with a diagnostic ultrasound system, decreased approximately a factor of 2 for increasing particle concentration from 10(8) to 10(10) particles/cc, with the lowest threshold of 5.24 MPa. For samples with gas saturations below 50% and 10(10) particles/cc, the average thresholds were at least twice as high as those of more saturated fluids (with mean threshold for saturated fluids of 6.45 MPa), and samples containing CO2 had considerably lower thresholds than respective under-saturations in air. At a fixed pressure amplitude, echogenicity tended to increase with both increasing particle concentration and gas saturation; this was more favorable for samples containing CO2. Even in a restricted-nuclei environment such as the urinary bladder, generation of vaporous cavitation should be possible; however, subsequently, abundant gas is needed to grow vaporous bubbles to persistent and imageable sizes, to assist in the diagnosis of urinary reflux.

A surgical reflux procedure, performed on two canines, was used to test a less invasive method for diagnosing urinary reflux. After approximately 6 weeks of recovery, examinations tested for reflux over the next 7 weeks. The canines were positioned prone (slightly head down) on a tilted table with a hole exposing the depilated abdomen, where a 1.18 MHz high intensity focused ultrasound transducer could be coupled. The reflux condition was evaluated first using standard fluoroscopy and x‐ray contrast instilled in the bladder by a gravity feed through a transurethral catheter. For high grade reflux, dilute contrast agent (Optison) was tested using harmonic color Doppler at 3 MHz on a Toshiba Powervision 8000 scanner imaging the kidney. Finally, aqueous solutions with elevated CO2 were placed in the bladder and microbubbles generated using a 10 s application of 1.18 MHz ultrasound (25 cycle bursts with 0.5% duty factor and 8.4 MPa). Bubbles were detected in the kidney on two occasions with strong color Doppler signal, near that from dilute Optison. Methods can naturally produce evelated CO2, and contrast bubbles should be producible transcutaneously for reflux diagnosis without ionizing radiation and catheterization. [Work supported in part by a USPHS grant 2 RO1DK42290.]