# Biogenic Gas Nanostructures As Molecular Imaging Reporters For Ultrasound

> **NIH NIH R01** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2020 · $702,563

## Abstract

PROJECT SUMMARY/ABSTRACT
Ultrasound is among the world's most widely used biomedical imaging technologies due to its relative
simplicity, low cost and ability to visualize deep tissues with high spatial and temporal resolution. However,
ultrasound has historically had a small role in molecular and cellular imaging due to the lack of contrast agents
connected to specific aspects of cellular function such as gene expression. To address this limitation, we are
developing the first acoustic biomolecules – proteins that can be imaged with ultrasound. These constructs are
based on gas vesicles – a unique class of gas-filled proteins from buoyant photosynthetic microbes, which we
adapted as imaging agents for ultrasound in 2014. Since this key initial discovery, our laboratory has led the
development of the emerging field of biomolecular ultrasound by engineering the physical, chemical and
biological properties of gas vesicles to enable multiplexed imaging, cellular targeting and selective detection in
vivo. In parallel, we have worked on transplanting the genetic program encoding gas vesicles into heterologous
hosts, recently succeeding in doing so in commensal bacteria relevant to the mammalian microbiome, while in
parallel making initial progress on expressing gas vesicles in mammalian cells. In addition, we discovered that
gas vesicles can produce susceptibility-weighted MRI contrast erasable by ultrasound, providing an additional
readout modality with unique advantages. Here we propose to build on these insights to advance gas vesicles
as targeted nanoscale contrast agents, mammalian reporter genes and functional sensors for ultrasound. This
work will focus on engineering gas vesicle properties for long-term circulation and extravascular targeting
through the bloodstream, achieving robust expression of gas vesicles as reporter genes in mammalian cells,
developing nonlinear ultrasound pulse sequences to maximize the sensitivity of gas vesicle imaging, and
designing the first acoustic sensors of enzyme activity. The fundamental innovation contained in this research
is that gas vesicle are the first biomolecular, genetically engineered and encoded contrast agent of any kind for
ultrasound. As a result, they have the potential to transform this imaging modality analogously to the way
fluorescent proteins transformed optical microscopy.

## Key facts

- **NIH application ID:** 9872174
- **Project number:** 5R01EB018975-06
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Mikhail Shapiro
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $702,563
- **Award type:** 5
- **Project period:** 2019-03-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9872174

## Citation

> US National Institutes of Health, RePORTER application 9872174, Biogenic Gas Nanostructures As Molecular Imaging Reporters For Ultrasound (5R01EB018975-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9872174. Licensed CC0.

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