Hybrid Imaging Method Delivers Panoramic Scan of a Live Animal

A hybrid imaging technique, dubbed single-impulse panoramic photoacoustic computed tomography (SIP-PACT), combines light and ultrasound to provide a full cross-sectional view of a small animal’s internal functions in real time, with enough resolution and penetration to see active organs, flowing blood, circulating cells and firing neural networks.

In contrast to SIP-PACT, pure optical imaging methods can exhibit a poor depth-to-resolution ratio. Non-optical techniques for whole-body imaging of small animals can show a lack of spatiotemporal resolution or functional contrast.

Photoacoustic imaging uses light to induce cells to emit ultrasound waves. Advances in the technology now allow it to scan entire cross sections of a live mouse in real time for an entire body view in under a minute. Courtesy of Junjie Yao & Kara Manke, Duke University.

SIP-PACT combines high spatiotemporal resolution (125-µm in-plane resolution, 50-µs-per-frame data acquisition and 50- Hz frame rate), deep penetration (48-mm cross-sectional width in vivo), anatomical, dynamical and functional contrasts, and full-view fidelity.

Using SIP-PACT, researchers from Duke University and the California Institute of Technology (CalTech) imaged in vivo whole-body dynamics of small animals in real time and obtained clear sub-organ anatomical and functional details. They tracked unlabeled circulating melanoma cells and imaged the vasculature and functional connectivity of whole rat brains.

“Photoacoustic imaging has been highly expected to get real-time whole-body imaging of a small animal with rich functional information,” said professor Junjie Yao. “With this advance, researchers can easily watch as drugs are distributed throughout an animal and track how different organs respond.”

A live look at the inner workings of a mouse’s intestines using photoacoustic imaging, which uses light to induce cells to emit ultrasound waves. Courtesy of Junjie Yao & Kara Manke, Duke University.

Researchers added speed and panoramic views to existing photoacoustic imaging techniques to create SIP-PACT. They built a circular ultrasonic detector and a fast data-acquisition system that can triangulate the origin of an ultrasonic wave from anywhere within the body of a small animal. With the help of a fast laser that operates within the safety limit, the device can image the full cross section of an adult rat 50 times per second, providing detailed movies of its inner workings with 120-µm resolution.

“The panoramic effect provides information from all directions and all angles, so you do not lose any information from each laser shot,” said Yao. “You can see the dynamics of the body in action — the pumping of the heart, the dilation of arteries, the functioning of various tissues.

“This approach is especially powerful because it does not rely on the injection of any type of contrast agent,” Yao said. “You can be sure that changes are not caused by foreign variables.”

SIP-PACT holds potential for both preclinical imaging and clinical translation.

“This penetration range enables functional imaging of whole bodies of small animals. This capability is expected to enable all kinds of biological studies in small animals and to accelerate drug discovery,” said professor Lihong Wang of CalTech.

This live look at a mouse’s brain tracks neurons firing by measuring oxygen levels, much like a functional magnetic resonance imaging (fMRI) scan. This image, however, was created with photoacoustic imaging that uses light to induce ultrasound waves, resulting in a color image that can reveal functional information such as the amount of oxygen present. Courtesy of Junjie Yao & Kara Manke, Duke University.

The research was published in Nature Biomedical Engineering (doi:10.1038/s41551-017-0071).