Bringing Optical Color to Ultrasound

Through a clever combination of two imaging modalities, scientists from Caltech and USC have developed a new technique that can quickly provide 3D color images that capture both the structure of soft tissues and details of how the blood vessels are functioning. The researchers have used the new technique to successfully image multiple parts of the human body. The method holds promise for enhancing breast tumor imaging, monitoring of nerve damage caused by diabetes, and brain imaging, among other applications.

The team describes the new technique in a paper that appears in the January 16 issue of Nature Biomedical Engineering.

Traditional ultrasound provides structural information quickly and inexpensively, but it has a limited field of view and only shows morphology in two dimensions. Meanwhile, photoacoustic imaging, has somewhat opposite benefits and challenges. It involves sending laser light into the body and measuring the sound waves that come out. It helps physicians and researchers see molecules in the vasculature in optical color—allowing for visualization of how blood is flowing through veins and arteries. However, photoacoustic imaging is insufficient when it comes to structural detail.

Other imaging tools such as computed tomography (CT) scanning and magnetic resonance imaging (MRI) have their own drawbacks: They require contrast agents, are expensive, involve the use of ionizing radiation, or are too slow for repeated regular use.

Enter RUS-PAT (rotational ultrasound tomography, RUST, combined with photoacoustic tomography, PAT). Lihong Wang, the Bren Professor of Medical Engineering and Electrical Engineering and the Andrew and Peggy Cherng Medical Engineering Leadership Chair at Caltech, developed PAT more than 20 years ago. Through PAT, molecules in the tissue that absorb optical light are imaged because they begin to vibrate when hit with pulsed laser light, generating acoustic waves that can be measured and converted into high-resolution images.

Wang, who is also the executive officer for medical engineering at Caltech, says his group's aim with the current work was to combine the benefits of PAT with ultrasound. "But it's not like one plus one," he says. "We needed to find an optimal way of combining the two technologies."

Ultrasound typically uses many transducers to both generate and receive ultrasound waves, and combining this process directly with PAT would be too complex and expensive for widespread use. PAT, meanwhile, only requires the detection of ultrasound, and that gave Wang an idea. "I thought, 'Wait, can we just mimic light excitation of ultrasound waves in photoacoustic tomography, but do it ultrasonically?'" PAT allows laser light to diffuse within the tissue, ultimately triggering the production of measurable ultrasound waves. Similarly, Wang figured, they could use a single wide-field ultrasound transducer to broadcast an ultrasonic wave broadly into the tissue.

They could then use the same detectors to measure the resulting waves for both modalities. In the new system, a small number of arc-shaped detectors are rotated around a central point, allowing it to behave like a full hemispheric detector but at a fraction of the complexity and cost.

"The novel combination of acoustic and photoacoustic techniques addresses many of the key limitations of widely used medical-imaging techniques in current clinical practice, and, importantly, the feasibility for human application has been demonstrated here in multiple contexts," says Dr. Charles Y. Liu, an author of the paper who is a visiting associate in biology and biological engineering at Caltech. Liu is also a professor at the Keck School of Medicine of USC, director of USC's Neurorestoration Center, and chair of neurosurgery at the Rancho Los Amigos National Rehabilitation Center.

The RUS-PAT technique could potentially be used in any region of the body to which light can be delivered, and for applications where clinicians or researchers would benefit from the synergistic imaging of both the morphology and color-related function. For example, RUS-PAT could improve breast-tumor imaging, giving physicians the ability to know a tumor's exact location and surroundings as well as its pathology and physiology. It could also help doctors monitor the nerve damage caused by diabetic neuropathy by providing an all-in-one way to monitor oxygen supply along with morphology. Wang says the technique could also be useful in brain imaging, allowing scientists to observe the structural details of the brain while also being able to observe hemodynamics.

Currently, the system can scan to a depth of about 4 centimeters. Light can also be delivered endoscopically, potentially making deeper tissues accessible to the new technology. A RUS-PAT scan can be performed in less than one minute.

The current setup involves a scanning system with ultrasound transducers and laser housed underneath a bed. It has been demonstrated on human volunteers and patients and is in the early stages of translational development.

The paper is titled "Rotational ultrasound and photoacoustic tomography of the human body." The co-lead authors of the paper are Yang Zhang, Shuai Na, and Dr. Jonathan J. Russin. Zhang and Na completed the work as postdocs at Caltech and are now at Tsinghua University and Peking University in Beijing, respectively. Russin is from the Keck School of Medicine of USC and Rancho Los Amigos National Rehabilitation Center in Downey, California. Additional Caltech authors are Karteekeya Sastry, Li Lin (PhD '20), Junfu Zheng, Yilin Luo, Xin Tong (MS '21), Yujin An, Peng Hu (PhD '23), and former research scientist Konstantin Maslov. Lin is now at Zhejiang University in Hangzhou, China. Dr. Tze-Woei Tan is a co-author from the Keck School of Medicine of USC. The work was supported by funding from the National Institutes of Health.