# Monodisperse Microbubbles for Noninvasive Pressure Estimation

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 2022 · $610,292

## Abstract

Project Summary
The current clinical standard for quantifying fluid pressures relies on the invasive placement of pressure
catheters or needles. These measures are costly and not without risk, thereby reducing how often data is
collected. Ultrasound contrast agents (UCA) are gas-filled microbubbles that, when insontated at a
fundamental frequency (f0), act as nonlinear oscillators, generating signal components ranging from the
subharmonic (f0/2) through higher harmonics. The subharmonic amplitude of UCA exhibits a linear relationship
with hydrostatic pressure, leading to the technique of subharmonic-aided pressure estimation (SHAPE).
SHAPE optimizations to date have relied primarily on empirical evidence to identify optimal acoustic
parameters and select a commercially available UCA. Currently, SHAPE provides up to 14 dB reduction in the
subharmonic amplitude over a pressure increase of 180 mmHg (0.6 dB/kPa). Clinical trials using SHAPE for
the diagnosis of portal pressures, cardiac pressures, and interstitial tumoral pressures during therapy have all
shown success. However, large variations in SHAPE have been observed at lower fluid pressures, indicating a
need to improve the technique's overall sensitivity. Using a variation of the Rayleigh–Plesset equation, our
group and others have modeled the SHAPE response of individual commercial bubbles and identified potential
sensitivities > 2 dB/kPa using optimized acoustic parameters. Thus, the potential exists to more than triple the
current sensitivity of SHAPE, thereby greatly reducing the overall errors associated with lower pressure
measurements.
Monodisperse microbubbles can be created using either buoyancy separation of existing UCAs or microfluidic
techniques. We hypothesize these agents will allow us to better refine previous modeling efforts, while also
greatly improving the overall sensitivity of SHAPE by tailoring the UCA to its application. To support this
hypothesis, we recently showed that monodisperse UCA nearly doubled the sensitivity of SHAPE (even
without full acoustic optimization). This proposal will be a first step towards the long-term goal of translating
SHAPE-specific UCA into clinical trials for improving the overall sensitivity of SHAPE as a noninvasive
pressure estimation technique. As part of this application, we propose to test the in vitro sensitivity of SHAPE
using monodisperse UCA using two fabrication approaches, to refine and validate our prior models of SHAPE
with empirical evidence from monodisperse UCA, and finally, to determine the ability of a customized,
monodisperse UCA to improve the sensitivity of SHAPE in in vivo models of cardiac pressures and portal
hypertension. At the conclusion of this project, we will have developed and validated a SHAPE-specific UCA,
capable of improving the sensitivity of SHAPE. These findings are expected to reduce the variability of SHAPE
as a noninvasive clinical measure of fluid pressures, enabling safer and more available clini...

## Key facts

- **NIH application ID:** 10520335
- **Project number:** 1R01EB032333-01A1
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** John Eisenbrey
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $610,292
- **Award type:** 1
- **Project period:** 2022-08-05 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10520335

## Citation

> US National Institutes of Health, RePORTER application 10520335, Monodisperse Microbubbles for Noninvasive Pressure Estimation (1R01EB032333-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10520335. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*