Novel CO2 Loaded Nanoparticle Ultrasound-Activated Contrast Agent: A Potential Urinary Catheter-Free Modality to Detect Vesicoureteral Reflux

• Published in: Journal of pediatric urology 2025-01
• Main Authors: Lavoie, Callum, Nussbaum, Zoe, Syed, Helal, Chun, Brian, Do, Van, Nguyen, Davin, Surapaneni, Anvi, Hamid, Ethan, Rayes, Adnan, De La Torre, Dominic, Ramirez, Oliver, Rosales, Eduardo, Williams, Travis J., Yen, Jesse T., Chang, Andy Y.
• Format: Article
• Language: English
• Subjects: Nanoparticle; Polyethyleneimine; Ultrasound; Vesicoureteral Reflux; VUR imaging
• ISSN: 1477-5131
• DOI: 10.1016/j.jpurol.2025.01.003

The current gold-standard for detecting vesicoureteral reflux (VUR) is the voiding cystourethrogram (VCUG). However, VCUGs require ionizing radiation and bladder catheterization that can be challenging to perform and traumatic for pediatric patients and their parents. To investigate the feasibility of a novel urinary catheter-free modality for diagnosing VUR using in vitro and ex vivo models. Polyethyleneimine (PEI) and pressurized CO2 gas were utilized to formulate our polymer in a standardized and reproducible method. The CO2-loaded PEI solution was stimulated using moderate intensity ultrasound in latex balloons and ev-vivo porcine bladders. Degassed, deionized water served as the control. A Butterfly iQ ultrasound imaging system connected to a 9th generation iPad was utilized to observe any effervescence (bubbles). In both the balloon and ex vivo bladder models, CO2 effervescence is reproducible and visualizable from the CO2-loaded polymer solution under US imaging after stimulation. We have demonstrated the ability to selectively release CO2 from CO2-loaded PEI nanoparticles to serve as an ultrasound contrast agent in both in vitro and ex vivo models. Future combined kidney-bladder porcine model experiments will be a critical step as we work towards validating and translating this agent as an effective modality for the diagnosis of VUR. In this feasibility study, we evaluated early pre-clinical models of a urinary catheter-free modality for the diagnosis of vesicoureteral reflux. We utilized a novel CO2-loaded nanoparticle solution that creates bubbles when activated with moderate intensity ultrasound. These bubbles were clearly visualizable with regular diagnostic ultrasound imaging in both a latex balloon and porcine bladder model.