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Biomedical Imaging and Instrumentation

Biomedical Imaging and Instrumentation - Poster Session E

Poster G1 - Ultrasound Release of CO2-loaded Polyethylenimine for Imaging Vesicoureteral Reflux

Saturday, October 26, 2024

10:00 AM - 11:00 AM EST

Location: Exhibit Hall E, F & G

Presenting Author(s)

Dominic De La Torre (he/him/his)

Biomedical Engineering: Molecular-Cellular Engineering Emphasis Undergraduate
University of Southern California
San Diego, California, United States

Co-Author(s)

ZN

Zoe Nussbaum (she/her/hers)

Research Lab Technician II
University of Southern California, United States
AS

Anvi Surapaneni

Research Assistant
University of Southern California, United States
EH

Ethan Hamid

Research Assistant
University of Southern California, United States
Travis Williams, PhD

Professor of Chemistry
University of Southern California, United States
AC

Andy Chang, MD

Associate Professor of Clinical Urology
University of Southern California
Los Angeles, California, United States

Primary Investigator(s)

JY

Jesse Yen

Associate Professor of Biomedical Engineering
University of Southern California, United States

Introduction: Vesicoureteral Reflux (VUR) is a urologic disease wherein urine flows backwards from the bladder into the ureters and kidneys. About 1-2% of all children are affected by this disease1, which can cause further complications such as greater risk of urinary tract infections and renal scarring if left untreated2. Currently, the diagnostic standard for VUR is a voiding cystourethrogram (VCUG). This involves urinary catheterization, which can be both emotionally and physically traumatic to young patients, and exposure to ionizing radiation3. Our research aims to improve diagnosis of VUR by creating a less invasive, catheter-free technique. This can be achieved by fabricating an IV-injectable CO2-loaded polyethylenimine (PEI) solution which will be filtered through the kidneys and to the bladder. The solution is then activated via focused ultrasound, and the CO2 is released to create bubbles. The resulting bubbles can then be imaged via standard ultrasound to show the direction of urine flow. From there, medical professionals will be able to diagnose whether a patient has VUR.

Materials and

Methods: To prepare the CO2-loaded PEI solution, 20-60 grams of PEI with varying molecular weights (800 Da, 1.8 kDa, 10 kDa, and 25 kDa) and varying percentages of sodium phosphate buffer (0%, 2.5%, 5%, and 7.5%, calculated as the ratio between the phosphorus to nitrogen atoms in this compound) are added to a Parr pressure reactor. The reactor is then sealed and pressurized to up to 800 psi with CO2 gas for 24 hours. Once removed from the reactor, the CO2-loaded PEI solution is diluted according to a 1:3 ratio with deionized water. This dilute CO2 loaded PEI solution is added to a pig bladder, which is suspended in a 37 degree Celsius water bath. A prototyped 1.1 MHz spherically-focused transducer with 55 mm focal depth connected to a computer powered RF generator is placed underneath the submerged pig bladder to provide the sonication necessary to release CO2. The generator transmits 10 W of electrical power to the transducer in a 1 ms on, 9 ms off power cycle for a total of 5 seconds. To image bubble coverage and reflux, a Butterfly iQ ultrasound imaging probe is placed vertically on the side of the bladder neck, where the urethra begins to narrow (Figure 1). MATLAB and ImageJ are then used on ultrasound trial images and videos to analyze the best atomic weight and buffer percentage of the CO2 loaded PEI solution.

Results, Conclusions, and Discussions: After extensive trials with all combinations of polyethylenimine atomic weight and sodium phosphate buffer percentage, Figure 2 shows that 10 kDa routinely out performed other atomic weights of PEI when it comes to bubble coverage. However, in regards to buffer percentage, the best sodium phosphate percentage to use in the PEI solution was unclear as this data was size dependent. Arguably, 10 kDa at 7.5% buffer would be best to use.
Moreover, after the PEI solution in the pig bladder was sonicated, the CO2 bubbles released from the loaded PEI solution are seen to go against the flow of gravity, up the urethra (Figures 3-5). Through the use of ImageJ analysis, it was determined that the bubbles of a 1.8 kDa PEI solution were traveling at a speed of 1.935 centimeters per second. While there was an attempt to image the upward flow of bubbles through a pig ureter, the small diameter of ureter tissue made it challenging to visualize the flow of bubbles. The CO2 bubbles being able to travel and imaged flowing upwards suggests that the backwards flow of urine, or reflux, can be done in vivo.
The results of this experiment demonstrate the potential to visualize the release of CO2 bubbles from PEI to image VUR and ultimately replace the emotionally and physically taxing standard of diagnosis. Further animal and human trials are needed in order to test the safety of CO2 loaded PEI as a contrast agent, how this solution can reach and exit the bladder when injected intravenously, and the best PEI solution to use in terms of bubble coverage and duration.

Acknowledgements (Optional):