# Scar Detection and Treatment with Droplet Activation

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2021 · $728,043

## Abstract

Project Summary
Commercially available phospholipid encapsulated perfluoropropane microbubbles can be compressed into
droplets that are submicron in size and remain in a liquid form within their shell even at body temperatures.
We have demonstrated that these shelled droplets have significantly different acoustic properties than the
microbubbles they are formed from, and can accumulate within a developing myocardial scar zone.
Moreover, we have vaporized these droplets with diagnostic high mechanical index (MI) transthoracic
ultrasound in small and large animal models of myocardial ischemia and reperfusion (I/R). We have now
demonstrated droplet presence within extravascular locations including the sarcoplasm following
intravenous injection after I/R. The diagnostic and therapeutic potential of selective activation/cavitation of
droplets within the developing scar zone (DSZ) will be explored in this application. The central hypothesis
of this project is that intravenously injected perfluoropropane droplets within the DSZ can be vaporized with
high MI diagnostic ultrasound, and that subsequent background-subtracted intensities will correlate with
droplet concentration. Furthermore, we project that activation and cavitation of these formed microbubbles
will increase tissue nitric oxide production, resulting in a reduction in the size of the DSZ. This proposal
seeks to address significant knowledge gaps that must be overcome to adequately test this hypothesis. The
diagnostic ultrasound thresholds for droplet vaporization must be determined, and what specific behavior
the formed microbubbles exhibit in terms of coalescence, cavitation, or re-condensation following
vaporization. We will employ an ultra-high speed (>106 Megahertz frame rate) camera to detect activation
(vaporization) thresholds and examine the formed microbubble behavior. We will utilize in vitro flow systems
with passive cavitation detectors to determine activation and cavitation thresholds in microvascular and
vascular flow conditions. We will analyze the microvascular location of droplets (vascular or extravascular)
under normal conditions and following I/R in the rat cremaster muscle. We will then apply selective
activation/cavitation pulses to the DSZ in a rat model of myocardial I/R. The selective activation of nitric
oxide activity within the scar zone will also be verified, and how it is affected by the timing of the applied
activation/cavitation impulses in relation to reperfusion. We will then assess the ability of selective
activation/cavitation to quantify infarct size in a large animal model of myocardial I/R. Finally, we will assess
the long-term therapeutic effect of selective activation/cavitation imaging of the DSZ following intravenous
injections of perfluoropropane droplets at different time points following reperfusion in porcine models of I/R.
This project will determine the potential for selective droplet activation and cavitation to detect the developing
scar zon...

## Key facts

- **NIH application ID:** 10133130
- **Project number:** 5R01HL146489-02
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** THOMAS R PORTER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $728,043
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133130

## Citation

> US National Institutes of Health, RePORTER application 10133130, Scar Detection and Treatment with Droplet Activation (5R01HL146489-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10133130. Licensed CC0.

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