# Gas microbubbles as a hyperpolarized-xenon carrier and as a contrast agent for MRI

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $225,891

## Abstract

Gas microbubbles have been widely used as ultrasound (US) vascular imaging agents and, more recently, for
targeted delivery of drugs and gases in vivo. Their safety profile and their potential as molecular imaging probes
make them ideal contrast agents also for MRI. Thus, considering the increase in US/MRI applications that could
benefit from a dual-modality contrast agent, gas microbubbles present a promising alternative to gadolinium or
iron-oxide based contrast agents.
Previous detection of gas microbubbles by MRI has focused primarily on the reduction of the transverse
relaxation time (T2 and T2*) of nearby water protons caused by magnetic susceptibility gradients generated at
the gas–liquid interface. However, these susceptibility effects are relatively weak. As a result, the microbubble
dosage required to obtain acceptable MR contrast is much higher than dosages typically used for clinical
ultrasound imaging.
We hypothesize that MR sensitivity to gas microbubbles can be enhanced significantly by using HyperCEST.
HyperCEST combines Chemical Exchange Saturation Transfer (CEST) and hyperpolarized xenon-129 (HPXe)
and can boost MR sensitivity by several orders of magnitude. This hypothesis is supported by recent studies
showing hyperCEST detection of gas nanovescicles at picomolar concentrations. Compared to gas
nanovescicles, microbubbles have increased xenon-host capacity, lower exchange rate, and a much narrower
frequency distribution, thus are expected to saturate hyperCEST detection sensitivity.
Additionally, we hypothesize that targeted delivery of gas microbubbles coupled with HPXe inhalation will
enhance HPXe signal from distal organs, thereby enabling dissolved-phase xenon MR applications that
capitalize on the relatively high solubility of this gas and its impressive sensitivity to its chemical environment.
These two hypothesis will be tested through the following specific aims: 1. To characterize and optimize the
physical and magnetic resonance properties of microbubbles as hyperCEST agents, in vitro and in vivo; 2. To
quantify HPXe signal amplification obtained from US-guided targeted delivery of gas microbubbles. If
successful, the proposed research will establish gas microbubbles as a safe and effective dual modality
US/MR contrast agent that can easily be disseminated to the research community and transformed into a
molecular imaging agent, ultimately resulting in clinical translation. Additionally, direct imaging of gas diffusion
in tissues by HPXe after US-assisted targeted release of microbubbles, will enable direct monitoring of
microbubbles delivery of biologically active gases and drugs.

## Key facts

- **NIH application ID:** 10196185
- **Project number:** 1R21EB031319-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Rosa Tamara Branca
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $225,891
- **Award type:** 1
- **Project period:** 2021-04-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10196185

## Citation

> US National Institutes of Health, RePORTER application 10196185, Gas microbubbles as a hyperpolarized-xenon carrier and as a contrast agent for MRI (1R21EB031319-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10196185. Licensed CC0.

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