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Using Gas Bubbles as Lenses to View Tissues More Deeply

A team of researchers at the Daegu Gyeongbuk Institute of Science and Technology (DGIST) have developed a method to improve the depth of the optical imaging of living tissues using a layer of ultrasound-created gas bubbles.

In a breakthrough by a research team led by Professors Jin Ho Chang and Jae Youn Hwang of the Department of Electrical Engineering and Computer Science at the Daegu Gyeongbuk Institute of Science and Technology (DGIST), a new laser scanning microscopy technique has been developed. It allows for clearer and deeper observation of internal tissues, with gas bubbles produced during scanning via ultrasound.

The uses of optical imaging technologies are widespread in both clinical practice and scientific research. Unfortunately, some limitations of this technique include the undesirable effect of optical scattering in the tissue, resulting in low light transmission. This limits the use of optical imaging techniques for broader applications.

In 2017, Professor Jin Ho Chang’s team realised that micrometre-scale gas bubbles were produced by tissues when subjected to high-intensity ultrasound. Thus, they created a technology based on the fact that gas bubbles created by ultrasonic waves result in optical scattering in the same direction as the propagation of incident light. This allows light to penetrate more deeply into the tissues.

In addition, the research teams of Professors Jin Ho Chang and Jae Youn Hwang have collaborated to look into the development of alternative applications of optical imaging technology enhanced by gas bubbles produced by ultrasound.

They aimed to improve existing optical imaging techniques like confocal fluorescence microscopy. A confocal fluorescence microscope is a device that only detects certain types of fluorescence signals produced at the focal plane of light, providing high-contrast and high-resolution images of microscale organisms such as cancer cells. Though it is the most commonly used microscope for biology research, one main limitation of the device is that the focus of the light is blurry when trying to view more than 100µm deep into the tissue, due to the light scattered by the internal portion of the tissue.

Thus, in order to improve the maximum imaging depth of confocal fluorescence microscopy, photons from the light source must be able to withstand distortion from light scattered by tissues. The team collaboration resulted in a confocal fluorescence microscope with integrated ultrasound technology that creates and maintains a dense layer of bubbles, of 90 per cent density or more, within the living tissue, for the duration of the imaging. The gas bubble layer ensures that the incoming protons from the light source are not distorted from their original propagation direction. As a result, the newly-developed confocal fluorescence microscopy technique, named the UltraSound-induced Optical Clearing Microscopy (US-OCM), was able to image tissues up to six times deeper compared to the current confocal fluorescence microscopy methods.

The US-OCM used in the study was suggested to be harmless to the tissue as the generated gas bubbles vanished upon stopping the ultrasonic waves, and the tissues returned to their original state.

Professor Jin Ho Chang commented, “Through close collaboration with ultrasound and optical imaging experts, we were able to overcome the inherent limitations of existing optical imaging and treatment technologies. The technology secured through this study will be applied to various optical imaging techniques including multiphoton microscopy and photoacoustic microscopy in addition to several optical therapies including photothermal therapy and photodynamic therapy. This would enhance the application of existing technologies by increasing their image and treatment depth.” [APBN]

Source: Kim et al. (2022). Deep laser microscopy using optical clearing by ultrasound-induced gas bubbles. Nature Photonics, 1-7.