An Ultrasound Activated Ultrasound Contrast Agent for Urinary Imaging

Vesicoureteral reflux is the improper flow of urine from the bladder up to the kidneys, leading to kidney infection, scarring, and renal damage. The gold standard for diagnosis involves kidneys by X-ray. The process is extremely traumatic to children and parents. Thus, pediatricians have altered clinical practice to minimize the number of tests, and the NIH has established this problem as a national healthcare research priority. We are developing a new platform technology to enable catheter-free urologic and radiologic examinations. We’re using amine-based CO2 capture technology to develop a new ultrasound contrast agent that will be a novel system of detection, obviating catheterizations and radiation exposure for children screened for VUR. In this MHI pilot project, we will develop procedures for the preparation of a nanoparticle agent in which an ultrasound contrast is created by acoustically activated release of captured CO2. We currently have demonstrated the manufacture of our CO2-loaded nanoparticle materials, ultrasound- mediated release of CO2 from these materials, and imaging of the materials upon activation by ultrasound. With seed funds from CHLA’s FDA-CTIP program, we are proceeding to our first in vivo demonstration of concept this spring. MHI funding will enable us to tune the chemistry of our CO2 carrier, optimize ultrasound delivery and imaging probes and methods, and ultimately proceed to a larger, more meaningful in vivo experiment. The result of this investigation will open the way for clinical development of our technology platform in follow- up SBIR and R01/21 projects. We anticipate that the resulting chemical technology will be applicable to problems beyond the VUR application, including pressure flow studies, urodynamics, and selective drug delivery.