In modern medicine, doctors can use a variety of technologies to peer inside their patients to detect and monitor the signs of disease. Methods such as X-ray imaging and ultrasound imaging are well known to the public, but researchers are also developing new imaging methods of unprecedented speed and sensitivity, by creatively combining ideas from physics, chemistry, and biology.
A breakthrough in an emerging technology known as optoacoustic imaging has been announced by a team of researchers from Nanyang Technological University, Singapore (NTU Singapore) and Soochow University in China. Writing in the journal Nature Communications, the team showed that they can simultaneously detect different types of biologically active chemicals, known as free radicals, by measuring sound waves emitted by nanoparticles in the body. The new technique can discriminate precisely between different conditions, allowing for the quick and accurate detection of tumours, liver disease, and even alcohol or drug intoxication.
Professor Bengang Xing (center) and his research team have developed a molecular probe that enables a new and improved form of optoacoustic imaging. Photo credit: M. Fadly.
“Optoacoustic imaging can monitor, in real time, the faint traces of certain chemicals in the body, without the need for a traditional blood test,” explains Associate Professor Bengang Xing, a chemistry researcher at NTU who led the study. “Our laboratory designs molecular probes, known as nanoparticles, that interact with specific biomarkers doctors are interested in. When the nanoparticles are injected into the body and illuminated with near-infrared light, they emit ultrasonic waves, which are easily detected from outside the body. The procedure is very safe, since the three components — trace nanoparticles, infrared light, and ultrasound — are all harmless to the body.”
Optoacoustic images showing the inflammation of a mouse liver caused by a dose of tacrine. The new technique can accurately detect two different free radicals (top and bottom rows) at different times (left and right columns).
Figure credit: X. Ai et al.
The Xing laboratory teamed up with the group of Professor Mingyuan Gao in Soochow University to develop and test a new optoacoustic imaging method, utilising a nanoparticle specially designed to interact with two indicator molecules at the same time. The researchers targeted two types of free radicals, biologically active mediator molecules known to appear in different concentrations in healthy and diseased tissue. Since the different free radical interactions produce ultrasonic waves at different frequencies, their relative concentrations can be precisely determined. The researchers hoped that this “dual-channel” scheme would provide a more informative and useful measurement signal.
The tests, performed at the Gao laboratory in Soochow University, surpassed all expectations. In one experiment, mice were injected with either lipopolysaccharide (a toxin commonly produced by bacterial infections) or tacrine (a drug used to treat Alzheimer’s disease). Both injections cause liver inflammation, accompanied by the accumulation of free radicals. Optoacoustic imaging was able to show precisely where in the liver the free radicals appeared. Moreover, by comparing the relative concentrations of free radicals, the team could clearly distinguish between the two causes of inflammation (lipopolysaccharide or tacrine).
The NTU team. From left: Xiangzhao Ai, Zhimin Wang, Bengang Xing, and Haolun Cheong. Photo credit: M. Fadly.
The team also compared optoacoustic imaging to two standard blood tests for liver inflammation, and showed that their method can distinguish between different sources of liver inflammation more accurately than either blood test. Moreover, optoacoustic imaging can be performed repeatedly, as it does not require the drawing of blood, which allows the progression of liver inflammation to be easily monitored over time.
“Our team is continuing to refine the method,” says Associate Professor Xing. “We believe that it will soon be useful for medical diagnoses, such as the early detection of tumours, and for monitoring how patients respond to medical treatments.”
X. Ai, Z. Wang, H. Cheong, Y. Wang, R. Zhang, J. Lin, Y. Zheng, M. Gao, and B. Xing, Multispectral optoacoustic imaging of dynamic redox correlation and pathophysiological progression utilizing upconversion nanoprobes, Nature Communications 10, 1087 (2019).