North Carolina scientist Paul Dayton, PhD is in the final stages of a Foundation-funded study on the use of nanodroplets to improve the efficiency of focused ultrasound ablation.

Paul Dayton PhDThe nanodroplets assessed in the preclinical study were able to rapidly increase heating by more than 25 degrees Celsius at the target without peripheral heating. The results suggest that their nanodroplets are sufficiently stable to enhance FUS ablation for at least 1.5 hours, avoid skin burns, and are a better option over microbubbles. These nanodroplets could potentially reduce FUS procedure times by as much as five-fold by more quickly ablating a larger region of tissue without compromising safety.

Investigator Profile: Paul Dayton, PhD
Professor, Associate Department Chair, and Associate Director for Education for the Biomedical Imaging Research Center, Joint Department of Biomedical Engineering at University of North Carolina Chapel Hill and North Carolina State University, Raleigh.

Background
B.S. in Physics from Villanova University, M.E. in Electrical Engineering from the University of Virginia, Ph.D. in Biomedical Engineering from the University of Virginia.

BME Logo FINAL v2 sm

Research Interests
Ultrasound contrast imaging, ultrasound-mediated therapies, and medical devices.

Foundation Funded Project

Metastable Perfluorocarbon Nanodroplets for Enhanced HIFU Ablation

Brief Project Description
Our aim was to design an agent that could shorten ablation procedures without sacrificing safety. We designed and investigated a perfluorocarbon nanodroplet composed of a 1:1 ratio of dodecafluoropentane and decafluorobutane. This project was conducted in collaboration with the University of Virginia (UVA). After performing the in vitro work in North Carolina, the research team traveled to UVA to complete the study using their clinical system.

Paul Dayton_Research_Group

Q. What was the goal of your research?
We want to improve the efficiency of focused ultrasound. It is rapidly gaining recognition as a tool to replace invasive surgery with an incisionless procedure. Current treatment times are too long, which is a limitation because it is costly to occupy and operate an MRI machine for long periods of time. A nanoagent is a small droplet that travels to a target site. When you expose the droplet to ultrasound, it first converts to a bubble then oscillates. The oscillation greatly improves the conversion of the ultrasound energy into thermal energy. The conversion from a droplet to a bubble occurs at a specific energy threshold, which is the peak of the ultrasound focus. So the increased heating only occurs at that focus point.

Q. What are your results?
In our preliminary preclinical studies, the nanodroplets were able to increase heating by more than 25 degrees Celsius at the target site compared to treatment without the droplets, while at the same time avoiding peripheral heating. We observed better heating with the same amount of delivered energy. It was faster and did not damage other tissue. The study results suggest that our nanodroplets are sufficiently stable to enhance HIFU ablation in vivo for at least 1.5 hours, avoid skin burns, and are a better option over microbubbles. These nanodroplets could potentially reduce focused ultrasound surgical procedure times by as much as 5 fold by more quickly ablating a larger region of tissue without compromising safety.

Q: How has the Foundation helped to advance your research? Do you have any new funding opportunities on the horizon?
The Foundation provided the funds for the preclinical portion of the study. Our encouraging preliminary data will help us apply for NIH funding. With such convincing preliminary data, we can now make a competitive proposal.

Q: What comes next?
I would like to see progress in cancer. Focused ultrasound tumor ablation could potentially avoid the recovery time needed after an invasive surgery. These droplets could help in that area, possibly by using an EPR (enhanced permeability and retention) effect to target the tumors. We think our droplets will collect specifically in a tumor, which might make it easier to ablate. A logical next step might be to use this technology to treat veterinary patients. Some dogs get thyroid tumors, and this could be a good target for focused ultrasound because the tumors are fairly superficial. With ultrasound guidance and nanodroplet targeting, we could potentially get a clear image to treat a canine thyroid tumor.

Final Thoughts?
Nanodroplet molecules can be made with the same composition as FDA-approved ultrasound contrast agents, so they could be easily translated to currently approved agents (they’re just smaller).

To read more on this topic, this group recently published their paper entitled “Improving the performance of phase-change perfluorocarbon droplets for medical ultrasonography: current progress, challenges, and prospects” in Scientifica.

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