A superresolution localization photoacoustic microscopy (PAM) technique has been developed by a team at Pohang University of Science and Technology (POSTECH). The new system can monitor the flow of red blood cells without using a contrast absorber, enabling it to image blood vessels with exceptional resolution. Spatial resolution is improved by a factor of 2.5 in vivo, the team said. The new system uses a stable, commercially available galvanometer scanner with a custom-made scanning mirror. This novel hardware implementation enhances the temporal resolution of the microscope significantly while maintaining a high signal-to-noise ratio (SNR). The new system has a fast B-mode rate (500 Hz). The researchers used their system to photoacoustically and noninvasively observe the microvasculatures of small animals and humans in vivo. The blood flow rate in the microvasculatures was successfully monitored and quantified in vivo. The researchers were able to obtain microvascular images in human cuticles in just 2 seconds. They visualized the flow of red blood cells in a mouse ear and quantified the flow rate. They were able to apply the localization process to in vivo PAM images without any agent. Photoacoustic images of microvessels in the ears, eyes, and brains of mice captured by the newly developed photoacoustic microscopy. Courtesy of Chulhong Kim/POSTECH. Conventional PAM systems are hampered by limited temporal and/or spatial resolution. The POSTECH system, which can scan photoacoustic waves and optical beams simultaneously, shows promise as a tool for the diagnosis and treatment of stroke and cardiovascular disease. It can monitor and image the blood vessels with the flow of blood cells in real time, making it a potentially useful tool for diagnosing and treating urgent cases of vascular disease. Moreover, it allows direct monitoring of hemodynamics in the microvessels and could be applied in various fields including hemodynamic response. (Left) Photoacoustic image of microvessels in a mouse ear. (Center) Photoacoustic image obtained by applying the localization method without using a contrast absorber. It shows enhanced images of microvessels that cannot be seen with the conventional photoacoustic microscopy system. (Right) Three-dimensional image of the microvascular structure shown in the center image. Courtesy of Chulhong Kim/POSTECH. “We successfully imaged microvessels in the ears, eyes, and brains of mice and a human fingertip with this new photoacoustic microscopy system,” professor Chulhong Kim said. “What we have developed can be a complementary tool to the conventional brain imaging system and it can also be a promising tool for future preclinical and clinical studies.” The research was published in Light: Science & Applications (www.doi.org/10.1038/s41377-019-0220-4).