Generation of ultrasound contrast bubbles in in vivo canine urinary bladder for possible diagnosis of urinary reflux

A less invasive method for diagnosis of urinary reflux is being pursued using high intensity focused ultrasound (HIFU). Microbubbles produced in the urinary bladder, by transcutaneous application of HIFU, can be visualized with a diagnostic ultrasound system and the bubble movement can be tracked from the bladder, through the ureters, and to the kidney, if reflux occurs. Since urine is under-saturated in total gas and filtered by the kidney. It is necessary to increase the gas and/or particle content in the urine in order to produce contrast microbubbles at a minimal level of HIFU. In 5 canine experiments, sodium bicarbonate (0.0128 M/kg) was infused IV at 3 ml/min for 2 hours with Lasix(R). On average for 3 of 5 canines, the infusions resulted in a 63% increase in urine pCO₂ from the baseline (from saline infusion), with mean increase to 87 mmHg. This pCO₂ change decreased the threshold rarefactional pressure for imageable microbubble generation on average to 7.6 MPa (10 s exposure at 1.18 MHz, 25 cycles, 0.5% duty cycle) from 9 MPa (p-value=0.004). The elevated pCO₂, after bicarbonate infusion increased generated echogenicity 16-21 dB higher than for pristine urine or saline infusion for the same peak rarefactional pressure applied (p-value=0.002). And the longevity of the contrast was up to 12.1 seconds. Although these urine property modifications were done with IV administration, eventually urine manipulation should be possible with equivalent bicarbonate and Lasix(R) doses given orally. Therefore, manipulation of the urine gas content by intake of bicarbonate should be a safe and effective method to assist HIFU in generating copious imageable and residual microbubbles that can potentially be used for less invasive diagnosing urinary reflux